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1
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The Impact of Pre-Chemotherapy Body Composition and Immunonutritional Markers on Chemotherapy Adherence in Stage III Colorectal Cancer Patients. J Clin Med 2023; 12:jcm12041423. [PMID: 36835962 PMCID: PMC9962672 DOI: 10.3390/jcm12041423] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2023] [Revised: 02/05/2023] [Accepted: 02/07/2023] [Indexed: 02/15/2023] Open
Abstract
Patients with colorectal cancer (CRC) often fail to complete full-course chemotherapy with a standard dose due to various reasons. This study aimed to determine whether body composition affects chemotherapy adherence in patients with CRC. The medical records of 107 patients with stage III CRC who underwent adjuvant folinic acid, fluorouracil and oxaliplatin (FOLFOX) chemotherapy at a single center between 2014 and 2018 were analyzed retrospectively. Blood test results for selected immunonutritional markers were analyzed and body composition was measured through computed tomography. Univariate and multivariate analyses were performed on low and high relative dose intensity (RDI) groups, based on an RDI of 0.85. In the univariate analysis, a higher skeletal muscle index was correlated with a higher RDI (p = 0.020). Psoas muscle index was also higher in patients with high RDI than in those with low RDI (p = 0.026). Fat indices were independent of RDI. Multivariate analysis was performed for the aforementioned factors and results showed that age (p = 0.028), white blood cell count (p = 0.024), and skeletal muscle index (p = 0.025) affected RDI. In patients with stage III CRC treated with adjuvant FOLFOX chemotherapy, a decrease in RDI was related to age, white blood cell count, and skeletal muscle index. Therefore, if we adjust the drug dosage in consideration of these factors, we can expect an increased treatment efficiency in patients by increasing chemotherapy compliance.
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2
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Jang HR, Lee HY, Song SY, Lim KH. Clinical outcomes of targeted therapies in elderly patients aged ≥ 80 years with metastatic colorectal cancer. World J Clin Cases 2022; 10:10066-10076. [PMID: 36246797 PMCID: PMC9561573 DOI: 10.12998/wjcc.v10.i28.10066] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Revised: 07/26/2022] [Accepted: 08/17/2022] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND The 5-fluorouracil-based chemotherapy combined with oxaliplatin or irinotecan is usually used in colorectal cancer (CRC). The addition of a targeted agent (TA) to this combination chemotherapy is currently the standard treatment for metastatic CRC. However, the efficacy and safety of combination chemotherapy for metastatic CRC in patients aged above 80 years has yet to be established.
AIM To assess the clinical outcomes and feasibility of combination chemotherapy using a TA in extremely elderly patients with CRC.
METHODS Eligibility criteria were: (1) Age above 80 years; (2) Metastatic colorectal cancer; (3) Palliative chemotherapy naïve; (4) Eastern Cooperative Oncology Group performance status 0-1; and (5) Adequate organ function. Patients received at least one dose of combination chemotherapy with or without TA. Response was evaluated every 8 wk.
RESULTS Of 30 patients, the median age of 15 patients treated with TA was 83.0 years and that of those without TA was 81.3 years. The median progression-free survival (PFS) and overall survival (OS) in patients treated with TA were 7.4 mo and 15.4 mo, respectively, compared with 4.4 mo and 15.6 mo, respectively, in patients treated without TA. There was no significant difference in PFS (P: 0.193) and OS (P: 0.748) between patients treated with and without TA. Common grade 3/4 hematologic toxicities were anemia (16.7%) and neutropenia (10.0%). After disease progression, the median OS of patients who were treated with and without salvage chemotherapy were 23.5 mo and 7.0 mo, respectively, suggesting significant difference in OS (P = 0.001).
CONCLUSION Combination chemotherapy with TA for metastatic CRC may be considered feasible in patients aged above 80 years, when with careful caution. Salvage chemotherapy can help improve OS in some selected of these elderly patients.
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Affiliation(s)
- Hee Ryeong Jang
- Department of Internal Medicine, Kangwon National University Hospital, Kangwon National University School of Medicine, Chuncheon-si, Gangwon-do 24289, South Korea
| | - Hui-Young Lee
- Department of Internal Medicine, Kangwon National University Hospital, Kangwon National University School of Medicine, Chuncheon-si, Gangwon-do 24289, South Korea
| | - Seo-Young Song
- Department of Internal Medicine, Kangwon National University Hospital, Kangwon National University School of Medicine, Chuncheon-si, Gangwon-do 24289, South Korea
| | - Kyu-Hyoung Lim
- Department of Internal Medicine, Kangwon National University Hospital, Kangwon National University School of Medicine, Chuncheon-si, Gangwon-do 24289, South Korea
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3
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Tominaga T, Nonaka T, Oyama S, Shiraishi T, Takeshita H, Hisanaga M, Fukuoka H, Fukuda A, Sumida Y, Hashimoto S, To K, Tanaka K, Sawai T, Nagayasu T. Effect of oxaliplatin in elderly colon cancer patients with pathological T4 and/or N2 disease: a multicenter, propensity score-matched analysis. Int J Colorectal Dis 2022; 37:1181-1188. [PMID: 35478036 DOI: 10.1007/s00384-022-04159-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/17/2022] [Indexed: 02/04/2023]
Abstract
PURPOSE Although adjuvant chemotherapy (AC) using fluoro-pyrimidine and oxaliplatin (FU + oxaliplatin) is recommended after curative resection for locally advanced colon cancer patients, several randomized controlled trials have shown no additional effect of oxaliplatin in patients aged ≥ 70 years. Here, we examined the effectiveness of FU + oxaliplatin on the long-term outcome of old patients with a high risk of recurrence. METHODS This multicenter, retrospective study included 346 colon cancer patients diagnosed with pathological T4 and/or N2 disease from 2016 to 2020. They were divided into an old group (≥ 70 years, n = 197) and a young group (< 70 years, n = 167). Propensity score matching was used to minimize selection bias, and 126 patients per group were matched. RESULTS Before matching, the rates of poor performance status (p < 0.001) and the presence of comorbidities (76.1% vs. 47.9%, p < 0.001) were higher in the old group. Although all baseline factors were similar between groups, after matching, the AC rate was lower in the old group (45.2% vs. 65.1%, p = 0.002). In the old group, relapse-free (82.2% vs. 55.6% and 69.6%, p < 0.05) and overall survival (83.1% vs. 80.0% and 44.4%, p < 0.05) rates were significantly higher in the AC patients with FU + oxaliplatin than in the AC patients with only FU and the non-AC patients. CONCLUSION The selected old colon cancer patients with a high risk of recurrence gained an additional benefit with respect to prognosis from FU + oxaliplatin as AC.
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Affiliation(s)
- Tetsuro Tominaga
- Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Science, 1-7-1 Sakamoto, Nagasaki, Nagasaki, 852-8501, Japan.
| | - Takashi Nonaka
- Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Science, 1-7-1 Sakamoto, Nagasaki, Nagasaki, 852-8501, Japan
| | - Shosaburo Oyama
- Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Science, 1-7-1 Sakamoto, Nagasaki, Nagasaki, 852-8501, Japan
| | - Toshio Shiraishi
- Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Science, 1-7-1 Sakamoto, Nagasaki, Nagasaki, 852-8501, Japan
| | - Hiroaki Takeshita
- Department of Surgery, National Hospital Organization Nagasaki Medical Center, Ohmura, Nagasaki, Japan
| | - Makoto Hisanaga
- Department of Surgery, Isahaya General Hospital, Isahaya, Nagasaki, Japan
| | - Hidetoshi Fukuoka
- Department of Surgery, Isahaya General Hospital, Isahaya, Nagasaki, Japan
| | - Akiko Fukuda
- Department of Surgery, National Hospital Organization Ureshino Medical Center, Ureshino, Saga, Japan
| | - Yorihisa Sumida
- Department of Surgery, National Hospital Organization Ureshino Medical Center, Ureshino, Saga, Japan
| | - Shintaro Hashimoto
- Department of Surgery, Sasebo City General Hospital, Sasebo, Nagasaki, Japan
| | - Kazuo To
- Department of Surgery, Sasebo City General Hospital, Sasebo, Nagasaki, Japan
| | - Kenji Tanaka
- Department of Surgery, Saiseikai Nagasaki Hospital, Nagasaki, Nagasaki, Japan
| | - Terumitsu Sawai
- Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Science, 1-7-1 Sakamoto, Nagasaki, Nagasaki, 852-8501, Japan
| | - Takeshi Nagayasu
- Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Science, 1-7-1 Sakamoto, Nagasaki, Nagasaki, 852-8501, Japan
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4
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Abstract
Colon cancer is one of the most common cancers in the United States and is expected to rise as the prevalence of colon cancer is increasing with increasing aging population. Though some studies have shown benefits of chemotherapy in the elderly population, however, they are also at risk of drug toxicities. We searched major search engines including PubMed, Medline and EMBASE and reviewed articles published in the last 10 years. Here we present current treatment strategies available for the metastatic colon cancer in elderly patients.
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Affiliation(s)
- Muhammad Idrees
- Internal Medicine, Bassett Medical Center - Columbia University, Cooperstown, USA
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5
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Macaire P, Morawska K, Vincent J, Quipourt V, Marilier S, Ghiringhelli F, Bengrine-Lefevre L, Schmitt A. Therapeutic drug monitoring as a tool to optimize 5-FU-based chemotherapy in gastrointestinal cancer patients older than 75 years. Eur J Cancer 2019; 111:116-125. [PMID: 30849685 DOI: 10.1016/j.ejca.2019.01.102] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2018] [Revised: 01/21/2019] [Accepted: 01/27/2019] [Indexed: 10/27/2022]
Abstract
AIMS Most clinical trials exclude elderly people, leading to a limited understanding of the benefit-to-risk ratio in this population. Despite existing data regarding the oncological management of elderly receiving fluorouracil (5-FU)-based regimen, our objective was to investigate 5-FU exposure/toxicity relationship in patients ≥75 years and compare the effectiveness of 5-FU therapeutic drug monitoring between elderly and younger patients. METHODS Hundred fifty-four patients (31 of whom are older than 75 years) with gastrointestinal cancers, who were to receive 5-FU-based regimens, were included in our study. At cycle 1 (C1), the 5-FU dose was calculated using patient's body surface area, then a blood sample was drawn to measure 5-FU concentration and 5-FU dose was adjusted at the subsequent cycles based on C1 concentration. Assessments of toxicity were performed at the beginning of every cycle. RESULTS Seventy-one percent of elderly patients required dose adjustments after C1, compared with 50% for younger patients. Percentages of patients within 5-FU area under the curve range at cycle 2 were 64% and 68%, respectively, for elderly and younger patients. The proportion of elderly patients experiencing severe toxicities fell from 15% at C1 to only 5% at cycle 3. CONCLUSION Pharmacokinetic-guided 5-FU-dosing algorithm, leading to an improved tolerability while remaining within therapeutic concentration range, is even more valuable for patients older than 75 years than in younger patients.
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Affiliation(s)
- Pauline Macaire
- Pharmacy Department, Centre Georges-François Leclerc, 1 rue Pr. Marion, 21000 Dijon, France; INSERM U1231, University of Burgundy Franche-Comté, 7 Bd Jeanne d'Arc, 21000 Dijon, France
| | - Katarzyna Morawska
- Pharmacy Department, Centre Georges-François Leclerc, 1 rue Pr. Marion, 21000 Dijon, France
| | - Julie Vincent
- Medical Oncology Deparment, Centre Georges-François Leclerc, 1 rue Pr. Marion, 21000 Dijon, France
| | - Valérie Quipourt
- Department of Geriatrics and Internal Medicine, Hospital of Champmaillot, University Hospital, 21079 Dijon, France; Geriatric Oncology Coordination Unit in Burgundy, University Hospital, 21079 Dijon, France
| | - Sophie Marilier
- Department of Geriatrics and Internal Medicine, Hospital of Champmaillot, University Hospital, 21079 Dijon, France; Geriatric Oncology Coordination Unit in Burgundy, University Hospital, 21079 Dijon, France
| | - François Ghiringhelli
- INSERM U1231, University of Burgundy Franche-Comté, 7 Bd Jeanne d'Arc, 21000 Dijon, France; Medical Oncology Deparment, Centre Georges-François Leclerc, 1 rue Pr. Marion, 21000 Dijon, France
| | - Leila Bengrine-Lefevre
- Medical Oncology Deparment, Centre Georges-François Leclerc, 1 rue Pr. Marion, 21000 Dijon, France
| | - Antonin Schmitt
- Pharmacy Department, Centre Georges-François Leclerc, 1 rue Pr. Marion, 21000 Dijon, France; INSERM U1231, University of Burgundy Franche-Comté, 7 Bd Jeanne d'Arc, 21000 Dijon, France.
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6
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Bruera G, Russo A, Galvano A, Rizzo S, Ricevuto E. Clinical parameters to guide decision-making in elderly metastatic colorectal CANCER patients treated with intensive cytotoxic and anti-angiogenic therapy. Oncotarget 2018; 8:37875-37883. [PMID: 28053287 PMCID: PMC5514958 DOI: 10.18632/oncotarget.14333] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2016] [Accepted: 11/24/2016] [Indexed: 12/22/2022] Open
Abstract
INTRODUCTION Bevacizumab addiction to triplet chemotherapy, according to FIr-B/FOx schedule, as first-line treatment in young-elderly metastatic colorectal CANCER (MCRC) patients may be more effective. Tailored treatments show worse clinical outcome in unfit patients. METHODS Elderly patients were clinically evaluated according to age and comorbidity (Cumulative Illness Rating Scale) to select FIr-B/FOx regimen in fit or tailored treatments in unfit elderly. Limiting toxicity syndromes (LTS) were evaluated. RESULTS At 17 months follow-up, in 28 young-elderly patients treated with first line FIr-B/FOx: objective response rate (ORR) 79%, progression-free survival (PFS) 11 months, overall survival (OS) 21 months. Clinical outcome was not significantly different according to KRAS genotype. G3-4 toxicities were diarrhea 21%, mucositis 11%, neutropenia 11%. LTS were 46%, significantly more multiple than single site. At 8 months follow-up, in 37 unfit patients: ORR 37%, PFS 7 months, OS 13 months. PFS was significantly different in KRAS wild-type compared to mutant patients, while not OS. PFS and OS were significantly worse in KRAS c.35 G > A compared to wild-type and/or other mutant. CONCLUSIONS Careful decision-making process including evaluation of patient's fitness, and individual safety should be included to select FIr-B/FOx intensive first line regimen in young-elderly MCRC patients. KRAS, and specifically c.35 G > A mutant genotype, may significantly affect clinical outcome in patients unfit for FIr-B/FOx.
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Affiliation(s)
- Gemma Bruera
- Oncology Territorial Care, S. Salvatore Hospital, Oncology Network ASL1 Abruzzo, University of L'Aquila, L'Aquila, Italy.,Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy
| | - Antonio Russo
- Medical Oncology, Department of Surgical, Oncological and Stomatological Sciences, University of Palermo, Palermo, Italy
| | - Antonio Galvano
- Medical Oncology, Department of Surgical, Oncological and Stomatological Sciences, University of Palermo, Palermo, Italy
| | - Sergio Rizzo
- Medical Oncology, Department of Surgical, Oncological and Stomatological Sciences, University of Palermo, Palermo, Italy
| | - Enrico Ricevuto
- Oncology Territorial Care, S. Salvatore Hospital, Oncology Network ASL1 Abruzzo, University of L'Aquila, L'Aquila, Italy.,Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy
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7
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Beretta GD, Ferrari VD, Barni S, Pancera G, Labianca R. Medical Treatment of Colorectal Cancer in Elderly (>70 Years): Giscad Experience and Future Perspectives. TUMORI JOURNAL 2018; 88:S109-12. [PMID: 11989900 DOI: 10.1177/030089160208800133] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
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Abstract
BACKGROUND The management of elderly patients with cancer is influenced by several factors that can vary widely among aging individuals. As the proportion of elderly individuals increases, the need for specific care guidelines for this population is critical. The National Comprehensive Cancer Network (NCCN) has developed guidelines to address these factors when formulating optimal treatment regimens for elderly patients and to avoid significant toxicity and maintain their quality of life. METHODS Factors that influence the appropriate treatment choices for the elderly, such as functional status, comorbidity, polypharmacy, and the presence of anemia, are reviewed, and the guidelines developed by the NCCN for treatment elderly patients are discussed. RESULTS The guidelines address these factors when defining the goal of therapy and formulating individualized treatment approaches for the elderly to provide optimal care for these patients, avoid significant toxicity, and maintain their quality of life. CONCLUSIONS The goal of therapy must be clearly defined, whether survival, remission, cure, or palliation of symptoms. Enrollment of elderly cancer patients onto clinical trials is encouraged so the guidelines can be validated.
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Affiliation(s)
- Stuart M Lichtman
- Don Monti Division of Medical Oncology, North Shore University Hospital, Manhasset, NY 11030, USA.
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9
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Abstract
Background The number of individuals aged 65 years and older is growing rapidly, and the majority of cancers are diagnosed in this age group. Age-related changes in physiology can affect chemotherapy pharmacokinetics and pharmacodynamics in older patients. Methods We review the literature regarding the impact of age on the pharmacokinetics of commonly used chemotherapy drugs and discuss age-related changes in physiology and pharmacology that can affect chemotherapy tolerance in older patients. Results The data on age-related changes in chemotherapy pharmacokinetics are conflicting. While a few studies report age-related differences in chemotherapy pharmacokinetics, most found no significant difference or subtle differences in pharmacokinetics with aging. A difference in pharmacodynamics was commonly seen, however, with older patients at increased risk of myelosuppression and toxicity from age-related decline in organ function. The majority of these studies were performed in a small cohort of patients, thus limiting the generalizability of these results. Conclusions Additional studies are needed to address the pharmacokinetics and pharmacodynamics of cancer therapies in the older patient. Multicenter pharmacokinetic studies of adequate sample size, which include a thorough evaluation of physiologic factors and geriatric assessment parameters, would provide further insight into the factors affecting treatment tolerance. These studies would also help to guide appropriate chemotherapy dosing and interventions in order to maximize efficacy and minimize toxicity in the older patient.
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Affiliation(s)
- Arti Hurria
- Cancer and Aging Research Program, City of Hope National Medical Center, Duarte, CA 91010, USA.
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10
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Tominaga T, Nonaka T, Sumida Y, Hidaka S, Sawai T, Nagayasu T. Effectiveness of adjuvant chemotherapy for elderly patients with lymph node-positive colorectal cancer. World J Surg Oncol 2016; 14:197. [PMID: 27465031 PMCID: PMC4964014 DOI: 10.1186/s12957-016-0959-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2016] [Accepted: 07/22/2016] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND Several guidelines state that postoperative adjuvant chemotherapy (AC) confers survival benefits to patients with lymph node-positive colorectal cancer. However, older patients are usually not administered AC due to the higher risk of side effects. The aim of this study was to evaluate the benefit of AC for elderly patients (EP) and examine its tolerability. METHODS Data from 204 patients with lymph node-positive colon cancer were retrospectively analyzed. Patients were subdivided into two groups: EP, >75 years old (n = 53) and young patients (YP), <75 years old (n = 151). Clinicopathological features, type of chemotherapy, and outcomes were compared between groups. RESULTS Frequency of comorbidities and performance status were significantly higher in EP (p < 0.01 each), a greater proportion of YP (76 %) than EP received AC (40 %, p < 0.01), and YP received combination therapy more frequently than EP (p < 0.01). In terms of side effects, few EP showed severe side effects. Both YP and EP gained survival benefits from AC (p = 0.07 and p < 0.01, respectively). CONCLUSIONS AC should not be withheld from eligible EP purely because of age.
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Affiliation(s)
- Tetsuro Tominaga
- Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Science, 1-7-1 Sakamoto, Nagasaki, 852-8501 Japan
| | - Takashi Nonaka
- Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Science, 1-7-1 Sakamoto, Nagasaki, 852-8501 Japan
| | - Yorihisa Sumida
- Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Science, 1-7-1 Sakamoto, Nagasaki, 852-8501 Japan
| | - Shigekazu Hidaka
- Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Science, 1-7-1 Sakamoto, Nagasaki, 852-8501 Japan
| | - Terumitsu Sawai
- Department of Cardiopulmonary Rehabilitation Science, Nagasaki University Graduate School of Biomedical Science, 1-7-1 Sakamoto, Nagasaki, 852-8501 Japan
| | - Takeshi Nagayasu
- Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Science, 1-7-1 Sakamoto, Nagasaki, 852-8501 Japan
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11
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Geographic Variation in Oxaliplatin Chemotherapy and Survival in Patients With Colon Cancer. Am J Ther 2016; 23:e720-9. [DOI: 10.1097/mjt.0000000000000015] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
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Li S, Zhu L, Yao L, Xia L, Pan L. Association between ERCC1 and TS mRNA levels and disease free survival in colorectal cancer patients receiving oxaliplatin and fluorouracil (5-FU) adjuvant chemotherapy. BMC Gastroenterol 2014; 14:154. [PMID: 25175730 PMCID: PMC4156636 DOI: 10.1186/1471-230x-14-154] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2014] [Accepted: 08/21/2014] [Indexed: 01/22/2023] Open
Abstract
Background Aim was to explore the association of ERCC1 and TS mRNA levels with the disease free survival (DFS) in Chinese colorectal cancer (CRC) patients receiving oxaliplatin and 5-FU based adjuvant chemotherapy. Methods Total 112 Chinese stage II-III CRC patients were respectively treated by four different chemotherapy regimens after curative operation. The TS and ERCC1 mRNA levels in primary tumor were measured by real-time RT-PCR. Kaplan–Meier curves and log-rank tests were used for DFS analysis. The Cox proportional hazards model was used for prognostic analysis. Results In univariate analysis, the hazard ratio (HR) for the mRNA expression levels of TS and ERCC1 (logTS: HR = 0.820, 95% CI = 0.600 - 1.117, P = 0.210; logERCC1: HR = 1.054, 95% CI = 0.852 - 1.304, P = 0.638) indicated no significant association of DFS with the TS and ERCC1 mRNA levels. In multivariate analyses, tumor stage (IIIc: reference, P = 0.083; IIb: HR = 0.240, 95% CI = 0.080 - 0.724, P = 0.011; IIc: HR < 0.0001, P = 0.977; IIIa: HR = 0.179, 95% CI = 0.012 - 2.593, P = 0.207) was confirmed to be the independent prognostic factor for DFS. Moreover, the Kaplan-Meier DFS curves showed that TS and ERCC1 mRNA levels were not significantly associated with the DFS (TS: P = 0.264; ERCC1: P = 0.484). Conclusion The mRNA expression of ERCC1 and TS were not applicable to predict the DFS of Chinese stage II-III CRC patients receiving 5-FU and oxaliplatin based adjuvant chemotherapy.
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Affiliation(s)
- Sheng Li
- Oncology, Jiangsu Tumor Hospital, NO,42 bai zi ting, Nanjing 210000, China.
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13
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Bruera G, Cannita K, Giordano AV, Vicentini R, Ficorella C, Ricevuto E. Prognostic relevance of KRAS genotype in metastatic colorectal cancer patients unfit for FIr-B/FOx intensive regimen. Int J Oncol 2014; 44:1820-30. [PMID: 24715238 PMCID: PMC4063538 DOI: 10.3892/ijo.2014.2369] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2013] [Accepted: 02/07/2014] [Indexed: 11/06/2022] Open
Abstract
First-line triplet chemotherapy plus bevacizumab (FIr-B/FOx) can improve efficacy of metastatic colorectal cancer (MCRC), KRAS wild-type and mutant. Prognostic relevance of KRAS genotype was evaluated in patients unfit for FIr-B/FOx, treated with conventional medical treatments. Consecutive MCRC patients not eligible for FIr-B/FOx regimen due to age (≥75 years) and/or comorbidities were treated with tailored conventional first-line treatments. KRAS codon 12/13 mutations were screened by direct sequencing. Activity and efficacy were evaluated and compared according to medical treatments, age (non-elderly and elderly≥65 years), comorbidity stage (Cumulative Illness Rating Scale), metastatic extension (liver-limited and other/multiple metastatic), and KRAS genotype, using log-rank. Selected first line treatments were medical in 37 patients (92.5%), and surgical in 3 patients (7.5%). Medical treatment regimens: triplet, 18 (45%); doublet, 15 (37.5%); mono-therapy, 4 (10%). At median follow-up of 8 months, objective response rate (ORR) was 37%, median progression-free survival (PFS) 7 months, liver metastasectomies 8% (liver-limited disease 37.5%), median overall survival (OS) 13 months. Triplet regimens failed to significantly affect clinical outcome, compared to doublet. According to KRAS genotype, ORR, PFS and OS were, respectively: wild-type 50%, 8 months, 13 months; mutant 25%, 6 months, 9 months. KRAS genotype wild-type compared to mutant significantly affected PFS, while not OS. KRAS c.35 G>A mutation (G12D) significantly affected worse PFS and OS compared to wild-type and/or other mutations. KRAS genotype, specifically the c.35 G>A KRAS mutation, may indicate poor prognosis in MCRC patients unfit for intensive medical treatments.
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Affiliation(s)
- Gemma Bruera
- Medical Oncology, S. Salvatore Hospital, University of L'Aquila, I-67100 L'Aquila, Italy
| | - Katia Cannita
- Medical Oncology, S. Salvatore Hospital, University of L'Aquila, I-67100 L'Aquila, Italy
| | - Aldo Victor Giordano
- Radiology, S. Salvatore Hospital, University of L'Aquila, I-67100 L'Aquila, Italy
| | - Roberto Vicentini
- Hepatobiliar-Pancreatic Surgery, S. Salvatore Hospital, University of L'Aquila, I-67100 L'Aquila, Italy
| | - Corrado Ficorella
- Medical Oncology, S. Salvatore Hospital, University of L'Aquila, I-67100 L'Aquila, Italy
| | - Enrico Ricevuto
- Medical Oncology, S. Salvatore Hospital, University of L'Aquila, I-67100 L'Aquila, Italy
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14
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Effectiveness and safety of intensive triplet chemotherapy plus bevacizumab, FIr-B/FOx, in young-elderly metastatic colorectal cancer patients. BIOMED RESEARCH INTERNATIONAL 2013; 2013:143273. [PMID: 24307987 PMCID: PMC3838846 DOI: 10.1155/2013/143273] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/26/2013] [Revised: 08/31/2013] [Accepted: 09/13/2013] [Indexed: 12/30/2022]
Abstract
Four-drug regimens, such as FIr-B/FOx schedule, can improve efficacy of first-line treatment of metastatic colorectal cancer (MCRC) patients. The present study specifically evaluates feasibility of FIr-B/FOx first-line intensive regimen in fit young-elderly MCRC patients, representing approximately 40% of overall MCRC patients. Activity, efficacy, and safety were equivalent to overall MCRC patients, not significantly different according to KRAS genotype. Clinical outcome was significantly prolonged in liver-limited compared to other/multiple metastatic disease. Safety evaluation of the individual young-elderly patient showed that limiting toxicity syndromes (LTS) in multiple sites were significantly increased, compared to LTS in single site, with respect to non-elderly patients.
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15
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Leo S, Accettura C, Gnoni A, Licchetta A, Giampaglia M, Mauro A, Saracino V, Carr BI. Systemic treatment of gastrointestinal cancer in elderly patients. J Gastrointest Cancer 2013; 44:22-32. [PMID: 23150086 DOI: 10.1007/s12029-012-9447-5] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
PURPOSE Gastrointestinal cancer (GI) incidence increases with each decade of life and is the leading cause of death in patients aged >70 years. Nevertheless, elderly patients are often excluded or underrepresented in clinical trials. We performed a review of current recommendations in the management of GI elderly cancer patients. METHODS A comprehensive literature review was performed analyzing data about several meta-analysis and studies regarding chemotherapeutic regimens in elderly patients with colorectal and gastroesophageal cancers. RESULTS Most of the studies demonstrated that the elderly experience the same advantages and toxicities from chemotherapy as younger individuals despite the fact that the data reviewed in this article provide evidence that elderly with GI cancers are underrepresented in clinical trials and few trials are conducted addressing the different risks and aims in older population. Each individual should be assessed for an appropriate regimen of treatment in the adjuvant or metastatic gastrointestinal cancer setting, and the decision of how to treat elderly must incorporate goals and preferences of the patient after a careful discussion of risks and benefits. CONCLUSION Chronological age alone is not a sufficient factor to withhold curative/palliative treatment from an elderly GI cancer patient, and cofactors regarding their functional, social, and mental status have to be considered. For this purpose, several tools exist that may be utilized, such as geriatric assessment scores, comorbidity indices, frailty indices, scores for predicting toxicity from chemotherapy, and prognostic indices for survival.
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Affiliation(s)
- Silvana Leo
- Geriatric Oncology Unit-Medical Oncology Department, Vito Fazzi Hospital, Lecce, Italy.
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16
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Diakos CI, Chua W, Charles KA, Howell VM, Clarke SJ. Predicting chemotherapeutic response and toxicity in colorectal cancer. COLORECTAL CANCER 2013. [DOI: 10.2217/crc.13.39] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
SUMMARY While treatment for colorectal cancer has evolved significantly over the past 10 years with the introduction of active chemotherapeutic agents and targeted therapies, this has been at the cost of increased toxicity for patients; and significant financial burden for governments and patients. Predicting clinical outcomes, especially given the largely elderly patient population involved, is therefore paramount. This review seeks to summarize existing data regarding the prediction of response and toxicity to chemotherapy agents currently used in the treatment of colorectal cancer.
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Affiliation(s)
- Connie I Diakos
- Bill Walsh Translational Cancer Research Laboratory, Kolling Institute of Medical Research, University of Sydney, Royal North Shore Hospital, St Leonards, NSW, Australia
| | - Wei Chua
- Department of Medical Oncology, Liverpool Hospital, Liverpool, NSW, Australia
| | - Kellie A Charles
- School of Medical Sciences (Pharmacology), Sydney Medical School, University of Sydney, NSW, Australia
| | - Viive M Howell
- Bill Walsh Translational Cancer Research Laboratory, Kolling Institute of Medical Research, University of Sydney, Royal North Shore Hospital, St Leonards, NSW, Australia
| | - Stephen J Clarke
- Bill Walsh Translational Cancer Research Laboratory, Kolling Institute of Medical Research, University of Sydney, Royal North Shore Hospital, St Leonards, NSW, Australia.
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17
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Abstract
Pancreatic ductal adenocarcinoma (PDAC) is the fourth or fifth leading cause of death from cancer in Western industrialized countries. Surgical resection is the only chance of cure, but only 15-20 % of cases are potentially resectable at presentation, and despite complete resection, the overall prognosis remains relatively poor. Adjuvant therapy has modestly improved cure rates. The majority of patients with pancreatic cancer are over the age of 65 years. But this age group is underrepresented within clinical trials, and it is unknown whether older patients achieve similar results to younger ones in terms of survival and treatment tolerance. In addition, there are no clinical trials dedicated to the elderly. Retrospective studies coming from the non-resectable setting provide some understanding on outcomes in older patients with PDAC. To date, we can reasonably argue that selected elderly patients with PDAC can benefit from curative surgery and postoperative chemotherapy as do their younger counterparts, without a significant increase in morbidity and mortality. Gemcitabine should be preferred to 5-fluorouracil on the basis of a better risk-benefit balance.
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18
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Duffour J, Roca L, Bressolle F, Abderrahim A, Poujol S, Pinguet F, Ychou M. Clinical Impact of Intensified 5-Fluorouracil-Based Chemotherapy Using a Prospective Pharmacokinetically-Guided Dosing Approach: Comparative Study in Elderly and Non-Elderly Patients with Metastatic Colorectal Cancer. J Chemother 2013; 22:179-85. [DOI: 10.1179/joc.2010.22.3.179] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
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Recommendations and expert opinion on the adjuvant treatment of colon cancer in Spain. Clin Transl Oncol 2012; 13:798-804. [PMID: 22082644 DOI: 10.1007/s12094-011-0736-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
Adjuvant chemotherapy is the current standard in the management of patients with localised colon cancer (CC) following curative resection. The use of oxaliplatin plus 5 fluorouracil/leucovorin (FOLFOX) or oxaliplatin plus capecitabine-based (XELOX) regimens, both approved in Europe as adjuvant treatment for stage III CC, has improved prognosis in this stage, but questions on their usefulness in high-risk stage II or elderly CC patients and on the role of some prognostic biomarkers are still pending. In April 2010, a consensus meeting on adjuvant CC treatment based on a revision of the most recent literature was held in Spain. The panel considered the use of adjuvant chemotherapy for high-risk stage II CC patients to be justified. Additionally, the more convenient administration of oral fluoropyrimidines vs. IV continuous infusion 5-FU would make XELOX a more suitable alternative for the patient. A more cautious decision should be taken when prescribing oxaliplatin treatment in patients aged ≥70.
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20
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Abstract
Cancer incidence and mortality rise exponentially in the elderly. With the aging of the population there is an urgent need to address this issue with evidence-based guidelines. Delayed diagnosis and incomplete workup and treatment are well documented in this population. Incorporation of a geriatric evaluation in oncology practice should be routinely implemented to prevent adverse outcomes. Treatment decisions in the elderly should not be based solely on survival gains but should also take quality of life into consideration. Cancer treatment is safe and effective in the elderly population. Social issues and other comorbidities should be addressed to improve compliance and outcome. Many unanswered questions regarding the optimal management of elderly cancer patients can be addressed only with the new clinical trials. Eliminating age bias among health care providers by providing education will help achieve optimal care for the elderly with cancer.
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Affiliation(s)
- Deepak Kilari
- Department of Medicine, Hematology/Oncology, James P. Wilmot Cancer Center, University of Rochester, Rochester, NY 14642, USA
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21
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Berretta M, Zanet E, Nasti G, Lleshi A, Frustaci S, Fiorica F, Bearz A, Talamini R, Lestuzzi C, Lazzarini R, Fisichella R, Cannizzaro R, Iaffaioli RV, Berretta S, Tirelli U. Oxaliplatin-based chemotherapy in the treatment of elderly patients with metastatic colorectal cancer (CRC). Arch Gerontol Geriatr 2011; 55:271-5. [PMID: 21937127 DOI: 10.1016/j.archger.2011.08.016] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2011] [Revised: 08/22/2011] [Accepted: 08/23/2011] [Indexed: 12/23/2022]
Abstract
Elderly patients constitute a subpopulation with special clinical features that differ from those of the general population and are under-represented in clinical trials. We retrospectively analyzed the toxicity and efficacy of oxaliplatin-based chemotherapy in the treatment of elderly patients affected by metastatic (m) CRC. Seventy-five consecutive patients aged 65-75 years (median age 71 years), 51 males and 24 females, with mCRC and measurable disease, were analyzed. The primary site of metastases was the liver (38.6% of patients). The majority of patients had a performance status (PS) according to the Eastern Cooperative Oncology Group (ECOG) PS before treatment of 0-1 (96%). The overall response rate was 57.3%, median progression-free survival was 7 months and median overall survival was 27 months. The main hematological and extra-hematological toxicities (grade 3 or 4) were neutropenia (20.0%), and neurological toxicity or diarrhea (6.7%), respectively. No toxic death occurred. Oxaliplatin-based chemotherapy maintains its efficacy, and safety in elderly patients with mCRC and good PS. This regimen should be considered in the treatment of this particular setting of patients.
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Affiliation(s)
- Massimiliano Berretta
- Department of Medical Oncology, National Cancer Institute, IRCCS, Via Franco Gallini 2, I-33081 Aviano (PN), Italy.
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22
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Berretta M, Cappellani A, Fiorica F, Nasti G, Frustaci S, Fisichella R, Bearz A, Talamini R, Lleshi A, Tambaro R, Cocciolo A, Ristagno M, Bolognese A, Basile F, Meneguzzo N, Berretta S, Tirelli U. FOLFOX4 in the treatment of metastatic colorectal cancer in elderly patients: a prospective study. Arch Gerontol Geriatr 2011; 52:89-93. [PMID: 20211502 DOI: 10.1016/j.archger.2010.02.006] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2009] [Revised: 02/01/2010] [Accepted: 02/03/2010] [Indexed: 12/30/2022]
Abstract
Elderly patients constitute a subpopulation with special characteristics that differ from those of the general population and have been under-represented in clinical trials. We, prospectively, analyzed the toxicity and efficacy of the original FOLFOX4-regimen in the treatment of elderly patients affected by metastatic (m) colorectal cancer (CRC). Thirty-six consecutive patients aged 67-82 years (median age 72 years), 22 males and 14 females, with mCRC and measurable disease, were enrolled in the study. The primary site of metastases was the liver (36.1% of patients). The median ECOG Performance Status (PS) was 1. The main hematological and extra-hematological (grade 3 or 4) toxicities were neutropenia (38.9%) and neurological (13.9%), respectively. A total of 36 patients, aged 67-82 years were included. Twenty-two and 14 patients were male and female, respectively. The median age was 72 years (range 67-82). The primary site of metastases was the liver (36.1% of patients). The median ECOG Performance Status (PS) was 1. The overall response rate (ORR) was 44.4% and similar to original study. Median progression-free survival (PFS) was 7.5 months and median overall survival (OS) was 16 months. The main hematological and extra-hematological (grade 3 or 4) toxicities were neutropenia (38.9%) and neurological (13.9%), respectively. Tolerability, however, was manageable and no toxic death occurred. FOLFOX4-regimen maintains its efficacy, and safety ratio in elderly patients with mCRC and good performance status. It would be considered the treatment of choice in the treatment of this particular setting of patients.
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Affiliation(s)
- Massimiliano Berretta
- Department of Medical Oncology, Centro di Riferimento Oncologico, IRCCS, Via Franco Gallini 2, I-33081 Aviano (PN), Italy.
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Chua W, Kho PS, Moore MM, Charles KA, Clarke SJ. Clinical, laboratory and molecular factors predicting chemotherapy efficacy and toxicity in colorectal cancer. Crit Rev Oncol Hematol 2010; 79:224-50. [PMID: 20719530 DOI: 10.1016/j.critrevonc.2010.07.012] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2010] [Revised: 07/05/2010] [Accepted: 07/15/2010] [Indexed: 12/20/2022] Open
Abstract
Colorectal cancer (CRC) treatment has evolved significantly over the last ten years with the use of active chemotherapeutic agents including fluoropyrimidines, oxaliplatin and irinotecan plus targeted monoclonal antibodies bevacizumab, cetuximab and panitumumab. The addition of newer chemotherapeutic agents and targeted therapies has improved patient outcomes at the cost of increased toxicity with not all patients benefiting from these treatments. It is necessary for clinicians to more accurately predict clinical outcomes particularly in the predominantly elderly CRC patient population. This review aims to summarise existing data regarding the use of clinical and laboratory variables plus molecular markers in predicting response, survival and toxicity to chemotherapy agents and targeted monoclonal antibodies currently used in the treatment of CRC.
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Affiliation(s)
- Wei Chua
- Sydney Cancer Centre, Concord Repatriation General Hospital, Hospital Road, Concord, NSW 2139, Australia
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24
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Colon cancer. Crit Rev Oncol Hematol 2010; 74:106-33. [DOI: 10.1016/j.critrevonc.2010.01.010] [Citation(s) in RCA: 194] [Impact Index Per Article: 12.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2008] [Revised: 09/30/2009] [Accepted: 01/06/2010] [Indexed: 12/15/2022] Open
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25
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Maroun JA, Anthony LB, Blais N, Burkes R, Dowden SD, Dranitsaris G, Samson B, Shah A, Thirlwell MP, Vincent MD, Wong R. Prevention and management of chemotherapy-induced diarrhea in patients with colorectal cancer: a consensus statement by the Canadian Working Group on Chemotherapy-Induced Diarrhea. ACTA ACUST UNITED AC 2010; 14:13-20. [PMID: 17576459 PMCID: PMC1891194 DOI: 10.3747/co.2007.96] [Citation(s) in RCA: 97] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Chemotherapy-induced diarrhea (cid) is a common side effect of cancer treatment and can cause significant morbidity and mortality. Diarrhea is frequently severe enough to require a dose reduction of, a delay in, or a discontinuation of chemotherapy. Diarrhea-associated mortality has been reported to be as high as 3.5% in clinical trials of irinotecan and bolus 5-fluorouracil in colorectal cancer. The frequency of cid and its impact on patient management are frequently under-recognized in clinical practice.A Canadian working group, consisting of medical oncologists and an oncology pharmacist, was formed in 2001 to review the optimal approach to managing cid and to identify and implement new areas of research. The recommendations that follow are the result of the group's work.Acute medical management of cid includes loperamide or diphenoxylate as first-line agents. Subcutaneous octreotide is recommended for intractable grade 2 diarrhea and may be considered for grade 1 cid that does not resolve with high-dose loperamide. Hospitalization is recommended for patients with grades 3 and 4 cid; in-hospital care includes rehydration, antibiotic therapy, and octreotide.A chemotherapy dose reduction is generally advised for patients who have experienced grade 3 or 4 diarrhea in a previous chemotherapy cycle. If a dose reduction is not desired, prophylaxis with intramuscular long-acting release octreotide may be considered.The foregoing recommendations are based on expert opinion and require validation in prospective clinical trials.
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Affiliation(s)
- J A Maroun
- Ottawa Hospital Regional Cancer Centre, Ottawa, Ontario.
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26
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Pallis AG, Papamichael D, Audisio R, Peeters M, Folprecht G, Lacombe D, Van Cutsem E. EORTC Elderly Task Force experts' opinion for the treatment of colon cancer in older patients. Cancer Treat Rev 2009; 36:83-90. [PMID: 19944536 DOI: 10.1016/j.ctrv.2009.10.008] [Citation(s) in RCA: 42] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2009] [Revised: 10/28/2009] [Accepted: 10/29/2009] [Indexed: 02/07/2023]
Abstract
As a result of an increasing life expectancy, the incidence of colon cancer in the older population is rising. As a consequence oncologists and their older patients commonly face the dilemma of whether or not to give/receive treatment for colon cancer. However, the paucity of large, well conducted prospective trials makes it difficult to provide evidence-based clinical recommendations for these patients. The current evidence supports the safety and efficacy of treatment for colon cancer in fit older patients and demonstrates that treatment outcome can be similar to that of their younger counterparts. However, it should be noted that these data are derived from retrospective studies which are likely to suffer from selection bias. Despite a growing body of data, further work is still needed to establish optimal strategies to care for this special population and prospective specific trials for older colon cancer patients are clearly needed.
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Affiliation(s)
- A G Pallis
- EORTC Headquarters, EORTC-Elderly Task Force, Brussels, Belgium.
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27
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Abstract
Persons over the age of 65 are the fastest growing segment of the United States population. In the next 30 years, they will comprise over 20 percent of the population. Fifty percent of all cancers occur in this age group and, therefore, there will be an expected rise in the total cancer burden. Data is becoming available that will better guide the use of chemotherapy in the older patient population. Information regarding age-related physiologic changes are presented with their relationship to pharmacology, functional status, and hematopoiesis. Treatments are reviewed in regard to the adjuvant treatment of breast and colon cancer as well as primary therapy of aggressive non-Hodgkin's lymphoma. The treatment of more advanced breast, ovary and non-small cell lung cancer also are discussed.
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Affiliation(s)
- Tarun Wasil
- Department of Medicine, Memorial Sloan-Kettering Cancer Center, Commack, New York 11725, USA
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28
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Sastre J, Aranda E, Massutí B, Tabernero J, Chaves M, Abad A, Carrato A, Reina JJ, Queralt B, Gómez-España A, González-Flores E, Rivera F, Losa F, García T, Sanchez-Rovira P, Maestu I, Díaz-Rubio E. Elderly patients with advanced colorectal cancer derive similar benefit without excessive toxicity after first-line chemotherapy with oxaliplatin-based combinations: comparative outcomes from the 03-TTD-01 phase III study. Crit Rev Oncol Hematol 2008; 70:134-44. [PMID: 19111473 DOI: 10.1016/j.critrevonc.2008.11.002] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2008] [Revised: 08/20/2008] [Accepted: 11/05/2008] [Indexed: 12/12/2022] Open
Abstract
PURPOSE Healthy elderly patients with metastatic colorectal cancer may benefit from chemotherapy as much as the younger population. This analysis compares the outcomes of first-line oxaliplatin plus fluoropyrimidines in elderly versus young patients. PATIENTS AND METHODS 348 patients were randomized to capecitabine 1000 mg/(m2 12 h), days 1-14 plus oxaliplatin 130 mg/m2 day 1, every 3 weeks or weekly infusional 5-FU 2250 mg/m2 over 48 h plus bimonthly oxaliplatin 85 mg/m2. We evaluated response rate, time to progression, overall survival and toxicity according to age. RESULTS ORR for elderly and young patients were 34.9% and 44.7%, respectively (p=0.081). Median TTP did not differ between the two groups: 8.3 months for patients > or =70 years and 9.6 months for those <70 years (p=0.114). Median OS was 16.8 months and 20.5 months for the > or =70 and <70 years groups, respectively (p=0.74). With XELOX, mild paresthesia and an increase in transaminase levels were more frequent for young patients, whereas grade 3/4 diarrhea was higher in those > or =70 years (25% vs. 8%, p=0.005). For FUOX, only paresthesia was significantly lower in patients > or =70 years (53% vs. 71%, p=0.032). CONCLUSION Elderly patients with MCRC benefit from first-line oxaliplatin-fluoropyrimidine combinations as much as younger patients, without increased toxicity.
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Affiliation(s)
- Javier Sastre
- Servicio de Oncologia Medica, Hospital Clínico San Carlos, 28040 Madrid, Spain.
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Berretta M, Bearz A, Frustaci S, Talamini R, Lombardi D, Fratino L, Lleshi A, Bonanno S, Spartà D, Palmucci S, Berretta S, Tirelli U. FOLFOX2 in the Treatment of Advanced Colorectal Cancer: A Comparison Between Elderly and Middle Aged Patients. J Chemother 2008; 20:503-508. [DOI: 10.1179/joc.2008.20.4.503] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/30/2023]
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30
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La chimiothérapie dans les cancers colorectaux chez les sujets âgés. ONCOLOGIE 2008. [DOI: 10.1007/s10269-008-0844-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
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31
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Roque VMN, Forones NM. [Evaluation of the toxicity and quality of life in patients with colorectal cancer treated with chemotherapy]. ARQUIVOS DE GASTROENTEROLOGIA 2007; 43:94-101. [PMID: 17119662 DOI: 10.1590/s0004-28032006000200007] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/25/2005] [Accepted: 10/27/2005] [Indexed: 11/22/2022]
Abstract
BACKGROUND The colorectal cancer is the fourth cause of cancer in Brazil and 5-fluorouracil is the drug most commonly used in the adjuvant or palliative treatment of this disease. AIM - Evaluating in patients with colorectal cancer and chemotherapy, the toxicity and the quality of life. PATIENTS AND METHODS From March 2001 and May 2003, 45 patients treated with colorectal cancer treated with 5-fluourouracil and folinic acid were followed closely during six cycles. The gastrointestinal and hematologic toxicity was analysed making use of the chart "Recommendations for the Graduation of Acute and Subacute Toxicity". After the end of each cycle of chemotherapy, the results were registered according to the respectives degrees that vary from 0 to 4. The quality of life was researched through the WHOQOL bref (World Health Organization Quality of Life) questionary that consists of 26 questions and 4 domains: physical, psychological, social relations and environmental, in the beginning, on the 3rd and 6th cycles of treatment. RESULTS Among the 45 patients, 28 were male, the average age was 58.4 years old (from 34 to 79 years old). According to the International Union Against Cancer classification, 34 patients (75.6%) had tumors stage II or III and 11 had tumors stage IV (24.4%), 64.4% were in the colon. In 57.7% the chemotherapy was adjuvant and in the others palliative. The toxicities more commonly found were nauseas (42%), diarrhea (38%), and neutropenia (15.7%). There was no significant difference among the degrees of toxicity in the different cycles as well as among the patients in adjuvant or palliative treatment. Significant alterations was found among the quality of life in the physical and psychological domains when the 1st and the 2nd or the 1st and the 3rd application of the test were done. Alterations of the quality of life were also found in the social domain when the first evaluation was compared with the last one. There was no difference between the quality of life and the treatment.
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Affiliation(s)
- Vanessa Maria Nunes Roque
- Setor de Oncologia, Disciplina de Gastroenterologia, Departamento de Medicina, Universidade Federal de São Paulo, UNIFESP, SP
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Pasetto LM, Basso U, Friso ML, Pucciarelli S, Agostini M, Rugge M, Sinigaglia G, Lise M, Sotti G, Monfardini S. Determining therapeutic approaches in the elderly with rectal cancer. Drugs Aging 2007; 24:781-90. [PMID: 17727307 DOI: 10.2165/00002512-200724090-00006] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2022]
Abstract
BACKGROUND To evaluate the toxicity and feasibility of pelvic radiotherapy (RT) and/or surgery in elderly patients with locally advanced low-lying rectal cancer. PATIENTS AND METHODS From November 1999 to November 2005, 51 patients aged >or=70 years who underwent RT for locally advanced low-lying rectal cancer were retrospectively examined. Variables considered were age, co-morbidities (evaluated according to the Charlson score and the Cumulative Illness Rating Scale-Geriatric [CIRS-G] score) and surgery versus no surgery. RESULTS The median age was 80 years (range 70-94 years) and the male : female ratio was 33 : 18. A total of 5.9% of patients were considered 'fit', 72.5% had one or more CIRS-G grade 1 or 2 co-morbidities and 21.6% had one or more CIRS-G grade 3 co-morbidities. 54.9% of patients underwent surgery and 45.1% underwent RT. Only 9 of 21 (42.8%) patients who underwent radical resection received the full course of adjuvant RT and only seven (50%) of all patients treated with RT alone received the full dose of therapy. Patients with one or more CIRS-G grade 3 co-morbidities reported similar numbers of grade 1-2 toxicities as patients with one or more CIRS-G grade 2 co-morbidities. CONCLUSION Notwithstanding the small number of patients analysed, the findings of this study indicate that elderly patients with rectal cancer and mild co-morbidities could probably receive the same treatment as fit elderly patients, given that tolerability appeared to be similar in both categories of patients. Neither age nor co-morbidities should be considered reasons to deny the patient the possible benefits of receiving complete treatment. Moreover, Multidimensional Geriatric Assessment should always be undertaken to help clinicians make better decisions about treatment. Further prospective trials are needed to confirm these results.
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Pasetto LM, Falci C, Compostella A, Sinigaglia G, Rossi E, Monfardini S. Quality of life in elderly cancer patients. Eur J Cancer 2007; 43:1508-13. [PMID: 17292603 DOI: 10.1016/j.ejca.2006.11.023] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2006] [Accepted: 11/30/2006] [Indexed: 10/23/2022]
Abstract
The incidence of most types of cancer is age-dependent and progressive ageing is rapidly increasing the number of elderly people who need treatment for cancer. Elderly patients (older than 70 years) present particular characteristics that make the choice of the correct treatment more difficult; for this reason, these patients are often undertreated and largely underrepresented in cancer trials making the experimental evidence on this topic even weaker. Only relatively recently has Health-Related Quality of Life (HRQoL) begun to be considered as one of the hard end-points for clinical cancer research in the elderly. Treatment of elderly cancer patients represents a typical situation where its assessment is particularly useful because of the expected toxicity of treatment and several unresolved methodological problems (higher frequency of illiteracy, worse compliance with the questionnaires, concomitant diseases, use of instruments not validated in the aged population). The aim of this review is to underline the importance detected by the too small number of studies on elderly QoL evaluation and the need in future trials either to improve QoL assessment in this subcategory of patients undergoing treatment for cancer or not, or find specific assessment tools to do it.
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Affiliation(s)
- Lara Maria Pasetto
- Istituto Oncologico Veneto, Medical Oncology Department, Via Gattamelata 64, 35128 Padova, Italy.
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34
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Gallego R, Sanchez N, Maurel J. Chemotherapy for elderly patients with advanced colorectal carcinoma. Expert Rev Anticancer Ther 2006; 6:795-800. [PMID: 16759169 DOI: 10.1586/14737140.6.5.795] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
There is an increasing need to redefine treatment strategies in elderly patients with advanced colorectal carcinoma since they constitute more than 50% of newly diagnosed patients. Taking into account that the vast majority of clinical trials in advanced colorectal carcinoma include patients up to 75 years old, it seems reasonable to consider those patients over 75 years as elderly. In general, 20% of patients have favorable factors (fewer than four liver nodules less than 5 cm in size) and are suitable for local treatments (surgery or local-ablative therapies). Additionally, 40% of patients have poor performance status or are severely disabled owing to geriatric syndromes and/or comorbid diseases (advanced stage) that preclude any treatment strategies. The remainder of patients (fit elderly patients not suitable for radical treatments) constitute the focus of this review.
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Affiliation(s)
- Rosa Gallego
- Medical Oncology Service, Villarroel 170, 08036, Barcelona, Catalonia, Spain
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Aparicio T, Mitry E, Sa Cunha A, Girard L. [Management of colorectal cancer of elderly patients]. ACTA ACUST UNITED AC 2006; 29:1014-23. [PMID: 16435509 DOI: 10.1016/s0399-8320(05)88176-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Affiliation(s)
- Thomas Aparicio
- Service d'Hépato-Gastroentérologie, Hôpital Bichat-Claude Bernard, 75018 Paris.
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Dobie SA, Baldwin LM, Dominitz JA, Matthews B, Billingsley K, Barlow W. Completion of therapy by Medicare patients with stage III colon cancer. J Natl Cancer Inst 2006; 98:610-9. [PMID: 16670386 PMCID: PMC3124351 DOI: 10.1093/jnci/djj159] [Citation(s) in RCA: 119] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Certain factors, such as race or age, are known to be associated with variation in initiation of adjuvant chemotherapy for stage III colon cancer, but little is known about what factors are associated with completion of adjuvant therapy. To determine whether predictors of initiation also predict completion, we analyzed Surveillance, Epidemiology, and End Results (SEER) program data linked to Medicare claims. We investigated mortality as a means to testing the validity of the completion measure that we created. METHODS We studied 3193 stage III colon cancer patients whose diagnosis was recorded in 1992-1996 SEER program data linked to 1991-1998 Medicare claims and who initiated adjuvant chemotherapy after colon cancer resection. We defined a measure of adjuvant chemotherapy completion as one chemotherapy administration claim in a month. We tested the validity of the created measure and its relation to 3-year cancer mortality adjusted for demographic, clinical, and environmental variables. We explored the association of patient characteristics and treating physician characteristics with chemotherapy completion by use of multivariable logistic regression modeling. RESULTS Of the 3193 patients, 2497 (78.2%) completed the course. Risk of cancer-related mortality was statistically significantly lower among those completing chemotherapy (relative risk = 0.79, 95% confidence interval = 0.69 to 0.89) than those with no adjuvant therapy. Patients who were female, widowed, increasingly elderly, rehospitalized, and living in certain regions were less likely to complete adjuvant chemotherapy than other patients. Race and other clinical, environmental, and physician characteristics were not associated with completion of therapy. CONCLUSIONS Factors associated with incomplete adjuvant chemotherapy may represent physical frailty, treatment complications, and lack of social and psychological support. Interventions to mitigate these influences are a logical next step toward increasing chemotherapy completion rates.
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Affiliation(s)
- Sharon A Dobie
- Department of Family Medicine, University of Washington, Seattle, WA 98195-6390, USA.
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Souglakos J, Pallis A, Kakolyris S, Mavroudis D, Androulakis N, Kouroussis C, Agelaki S, Xenidis N, Milaki G, Georgoulias V. Combination of irinotecan (CPT-11) plus 5-fluorouracil and leucovorin (FOLFIRI regimen) as first line treatment for elderly patients with metastatic colorectal cancer: a phase II trial. Oncology 2005; 69:384-90. [PMID: 16319509 DOI: 10.1159/000089992] [Citation(s) in RCA: 53] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2004] [Accepted: 06/24/2004] [Indexed: 12/15/2022]
Abstract
PURPOSE To evaluate the efficacy and tolerance of irinotecan (CPT-11) in combination with bolus and continuous infusion of 5-fluorouracil (5-FU) and leucovorin (LV) (FOLFIRI regimen) as first-line treatment of elderly patients with metastatic colorectal cancer (MCC). METHODS Thirty consecutive, previously untreated patients with metastatic colorectal cancer, aged (median 76 years; range 70-84) were enrolled. The performance status (WHO) was 0 in 8, 1 in 16 and 2 in 6 patients; 19 (63%) patients had prior surgery and 8 (27%) adjuvant chemotherapy. CPT-11 (180 mg/m(2) as a 90 min i.v. infusion) was administered on day 1, LV (200 mg/m(2) as a 2-hour i.v. infusion), 5-FU (400 mg/m(2)/d i.v. bolus followed by 600 mg/m(2)/d as a 22-hour i.v. continuous infusion) were given on days 1 and 2 every 2 weeks. RESULTS Complete response was achieved in one (3.3%) patient and partial response in 10 (33.3%) (overall response rate: 36.6%; 95% C.I.: 26.6-48.4%); 11 (36.6%) patients had stable disease and, 8 (26.6%) disease progression. The median duration of response was 7.5 months and the median time to disease progression 7.0 months. After a median follow-up period of 17 months, the median overall survival was 14.5 months. Main toxicities were: grade 3-4 neutropenia (n = 6; 20%), grade 3 thrombocytopenia (n = 1; 3.3%), grade 2 anemia (n = 9; 30%), grade 3-4 diarrhea (n = 5; 17%) and grade 3 asthenia (n = 3; 10%). There was one treatment-related death due to neutropenic sepsis. CONCLUSIONS The FOLFIRI combination is an active regimen with manageable toxicity as front-line treatment in patients above 70 years of age.
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Affiliation(s)
- J Souglakos
- Department of Medical Oncology, School of Medicine, University General Hospital of Heraklion, Crete, Greece
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Schuell B, Gruenberger T, Kornek GV, Dworan N, Depisch D, Lang F, Schneeweiss B, Scheithauer W. Side effects during chemotherapy predict tumour response in advanced colorectal cancer. Br J Cancer 2005; 93:744-8. [PMID: 16160693 PMCID: PMC2361647 DOI: 10.1038/sj.bjc.6602783] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
To investigate whether a relationship between chemotherapy-associated adverse events and treatment efficacy exists, we have analysed the toxicity, objective response and survival data of 303 patients with advanced colorectal cancer. Patients were divided into two groups: the first with beneficial effect (I, n=245), and the second with progressive disease (II, n=58). Differences in terms of incidence rates, type and severity of adverse events were analysed with univariate and multivariate models. The median number of side effects in group I was 6 vs 4 in group II (OR=1.342; P=0.0001). An inverse correlation between disease control and treatment tolerance was confirmed when side effects were analysed according to severity and type of treatment-associated toxicities (haematological: P=0.0005 vs nonhaematological P=0.0001). When median survival was analysed according to the number of adverse events, it was 10 (95% CI, 3–7), 16 (14–18), and 18 (16–20) months in case of 0–1, 2–5, and ⩾6 adverse events, respectively (P=0.01). In conclusion, the results of this analysis suggest that occurrence of side effects during chemotherapy in advanced colorectal cancer is an independent and reliable prognostic indicator for response and survival.
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Affiliation(s)
- B Schuell
- Division of Clinical Oncology, Department of Internal Medicine I, University Hospital, Vienna, Austria.
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39
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Kim JH, Oh DY, Kim YJ, Han SW, Choi IS, Kim DW, Im SA, Kim TY, Lee JS, Heo DS, Bang YJ, Kim NK. Reduced dose intensity FOLFOX-4 as first line palliative chemotherapy in elderly patients with advanced colorectal cancer. J Korean Med Sci 2005; 20:806-810. [PMID: 16224154 PMCID: PMC2779277 DOI: 10.3346/jkms.2005.20.5.806] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2005] [Accepted: 05/16/2005] [Indexed: 01/02/2023] Open
Abstract
To evaluate the toxicity and efficacy of a reduced dose intensity (mini-) FOLFOX-4 regimen as a first-line palliative chemotherapy in elderly patients (> or =70 yr of age) with advanced colorectal cancer, data from prospective databases at Seoul National University Bundang Hospital and Seoul Municipal Boramae Hospital were analyzed. A total of 20 patients were enrolled between January 2001 and August 2004, and were treated with oxaliplatin 65 mg/m2 on day 1, and with 2-hr infusions of leucovorin 150 mg/m2 followed by a 5-FU bolus (300 mg/m2) and 22-hr continuous infusions (450 mg/m2) for 2 consecutive days every 2 weeks until progression, unacceptable toxicity or patient refusal. Sixteen patients were evaluable for response with an overall response rate of 43.8%. Median progression-free survival was 4.8 months (95% CI: 3.0-6.7) and overall survival was 13.5 months (95% CI: 11.1-16.0). The main side effects were anemia and neutropenia, which were observed in 20.8% and 17.7%, respectively, of the total cycles administered. There were no grade 4 toxicities and only one patient suffered from febrile neutropenia. No grade 3 toxicities occurred except for anemia (5.2%) and vomiting (1.0%). In conclusion, the mini-FOLFOX-4 regimen was found to be well tolerated with acceptable toxicity, and to provide a benefit for elderly patients with colorectal cancer.
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Affiliation(s)
- Jee Hyun Kim
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Do-Youn Oh
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Yu Jung Kim
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Sae Won Han
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - In-Sil Choi
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Dong-Wan Kim
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Seock-Ah Im
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Tae-You Kim
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Jong-Seok Lee
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Dae-Seog Heo
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Yung-Jue Bang
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Noe Kyeong Kim
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
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Pasetto LM, Stefano T, Rossi E, Paris MK, Monfardini S. Treatment of stage IV colorectal carcinoma in elderly patients. Crit Rev Oncol Hematol 2005; 54:145-55. [PMID: 15843097 DOI: 10.1016/j.critrevonc.2004.12.003] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/14/2004] [Indexed: 11/17/2022] Open
Abstract
Colorectal adenocarcinoma ranks second as a cause of death due to cancer in the Western world. In Europe, 40% of patients with colorectal cancer are over 70 years old and the incidence increased through the 1980's. Without any treatment the median survival after the detection of liver metastases is approximately 9 months, depending on the extent of disease at the time of diagnosis but not on the patients age. In the elderly there are only few data apt to define the standard regimen in the advanced disease, but results seem similar to those observed in younger patients. As a result of exclusion criteria and screening, elderly patients entering clinical trials are usually a select group, with good performance status, access to transportation, and limiting numbers of coexisting conditions. This paper examines the factors pertinent to the small number of clinical trials designed for metastatic colorectal cancer in this group of persons.
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Affiliation(s)
- Lara Maria Pasetto
- Divisione di Oncologia Medica Direzione, Azienda Ospedale-Università, Via Gattamelata 64, 35128 Padova, Italy.
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Wasil T, Lichtman SM. Clinical Pharmacology Issues Relevant to the Dosing and Toxicity of Chemotherapy Drugs in the Elderly. Oncologist 2005; 10:602-12. [PMID: 16177284 DOI: 10.1634/theoncologist.10-8-602] [Citation(s) in RCA: 48] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Persons over the age of 65 years are the fastest growing segment of the U.S. population. In the next 30 years, they will comprise more than 20% of the population. Fifty percent of all cancers occur in this age group, and therefore, there is an expected rise in the total cancer burden. Data are becoming available that will better guide the use of chemotherapy in the older patient population. In this paper, information regarding age-related physiologic changes and their relationship to pharmacology, functional status, and hematopoiesis is presented. The adjuvant treatment of breast and colon cancer, as well as the primary therapy of aggressive non-Hodgkin lymphoma is reviewed. The treatment of more advanced breast, ovarian, and non-small cell lung cancer is also discussed.
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Affiliation(s)
- Tarun Wasil
- Division of Oncology, Long Island Jewish Medical Center, New Hyde Park, New York, USA
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Sastre J, Marcuello E, Masutti B, Navarro M, Gil S, Antón A, Abad A, Aranda E, Maurel J, Valladares M, Maestu I, Carrato A, Vicent JM, Díaz-Rubio E. Irinotecan in combination with fluorouracil in a 48-hour continuous infusion as first-line chemotherapy for elderly patients with metastatic colorectal cancer: a Spanish Cooperative Group for the Treatment of Digestive Tumors study. J Clin Oncol 2005; 23:3545-51. [PMID: 15908665 DOI: 10.1200/jco.2005.03.004] [Citation(s) in RCA: 80] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
PURPOSE Elderly patients constitute a subpopulation with special characteristics that differ from those of the nonelderly and have been underrepresented in clinical trials. This study was performed to determine the efficacy and safety of irinotecan (CPT-11) in combination with fluorouracil (FU) administered as a 48-hour continuous infusion twice a month in elderly patients. PATIENTS AND METHODS Patients > or = 72 years old with metastatic colorectal cancer, Eastern Cooperative Oncology Group performance status of 0 to 1, no geriatric syndromes, and no prior treatment were treated every 2 weeks with CPT-11 180 mg/m2 plus FU 3,000 mg/m2 in a 48-hour continuous infusion. RESULTS By intent-to-treat analysis, in 85 assessable patients, the objective response rate was 35% (95% CI, 25% to 46%), and stable disease was 33% (95% CI, 23% to 44%). Median time to progression was 8.0 months (95% CI, 6.0 to 10.0 months), and median overall survival time was 15.3 months (95% CI, 13.8 to 16.9 months). Toxicity was moderate. Grade 3 and 4 neutropenia, diarrhea, and asthenia were observed in 21%, 17%, and 13% of patients, respectively. Only one case of neutropenic fever occurred. There were two toxic deaths, one was a result of grade 4 diarrhea and acute kidney failure, and the other was a result of massive intestinal hemorrhage in the first cycle. The study of prognostic factors did not reveal any predictive factor of response. Response to treatment and baseline lactate dehydrogenase were the main factors conditioning progression-free and overall survival. CONCLUSION Twice a month continuous-infusion CPT-11 combined with FU is a valid therapeutic alternative for elderly patients in good general condition.
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Affiliation(s)
- Javier Sastre
- Servicio de Oncología Médica, Hospital Clínico San Carlos, C/Profesor Martín Lagos, s/n, 28040 Madrid, Spain.
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Comella P, Gambardella A, Farris A, Maiorino L, Natale D, Massidda B, Casaretti R, Tafuto S, Lorusso V, Leo S. A tailored regimen including capecitabine and oxaliplatin for treating elderly patients with metastatic colorectal carcinoma Southern Italy Cooperative Oncology Group trial 0108. Crit Rev Oncol Hematol 2005; 53:133-9. [PMID: 15661564 DOI: 10.1016/j.critrevonc.2004.10.008] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/28/2004] [Indexed: 12/27/2022] Open
Abstract
From September 2001 to November 2002, 35 patients aged 70-81 (median, 75) years, with measurable metastatic lesions from colorectal carcinoma, were treated with a combination of oxaliplatin (OXA) infused i.v. over 2 h on day 1, and capecitabine, assumed orally twice a day (12-h apart) from day 2 to day 15. An alternated dose escalation for both drugs was planned over the first three cycles for each patient, in the absence of WHO grade > or =2 toxicity on previous cycle: starting doses were 85 mg/m2 for OXA, and 2000 mg/m2 (day) for capecitabine on first cycle; on second cycle, OXA was planned at 100mg/m2, while capecitabine was planned at 2500 mg/(m2 day) on third cycle. Treatment was repeated every 3 weeks until progression, or for a maximum of 12 cycles. A total of 212 cycles were administered, with a median of 6 (range, 1-12) cycles/patient. Dose escalation was performed in 18 (51%) patients for OXA, and in 4 (11%) patients for capecitabine. No grade 4, and 10 (29%) cases of grade 3 toxicity of any type were reported. Abdominal symptoms (pain, nausea, or vomiting) affected 66% of patients, but they were of grade 3 in only 2 (6%) patients. Grade 3 diarrhoea occurred in 3 (9%) patients. Two complete and 12 partial responses (PR) were reported, for an overall response rate of 40% (95% CI, 24-58%). Progression of disease occurred in 23 (66%) patients, and 18 (51%) died. The actuarial median progression-free and survival time were 6.9 and 14.1 months, respectively.
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Affiliation(s)
- Pasquale Comella
- Division of Medical Oncology A, Department of Medical Oncology, National Tumour Institute, Via M. Semmola, 80131 Naples, Italy.
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Abstract
Colon cancer is one of the leading tumours in the world and is considered among the big killers, together with lung, prostate and breast cancer. In the recent years very important advances occurred in the field of treatment of this frequent disease: adjuvant chemotherapy was demonstrated to be effective, chiefly in stage III patients, and surgery was optimized in order to achieve the best results with a low morbidity. Several new target-oriented drugs are under evaluation and some of them (cetuximab and bevacizumab) have already exhibited a good activity/efficacy, mainly in combination with chemotherapy. The development of updated recommendations for the best management of these patients is crucial in order to obtain the best results, not only in clinical research but also in everyday practice. This report summarizes the most important achievements in this field and provides the readers useful suggestions for their professional practice.
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O'Neil BH, Goldberg RM. Chemotherapy for advanced colorectal cancer: Let’s not forget how we got here (until we really can). Semin Oncol 2005; 32:35-42. [PMID: 15726504 DOI: 10.1053/j.seminoncol.2004.09.030] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
Physicians and patients alike have been heartened by the recent advances in the treatment of colorectal cancer. The emergence of novel agents that are active in the treatment of this devastating disease, such as cetuximab and bevacizumab, has been particularly notable. However, even before these recent events, a substantial change in prognosis for patients with metastatic colorectal cancer had occurred as a result of advances in traditional chemotherapeutic agents. Refinements in dose, schedule, and sequence continue to be made that could lead to further improvements in outcomes. Additionally, new chemotherapeutic agents with promise for activity in colorectal cancer are being studied. Chemotherapy is likely to remain a central element of the treatment strategy. Our understanding of its current role is discussed in this article.
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Affiliation(s)
- Bert H O'Neil
- UNC Lineberger Comprehensive Cancer Center, 3009 Old Clinic Building, CB #7305, Chapel Hill, NC 27599-7305, USA.
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46
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D'Andre S, Sargent DJ, Cha SS, Buroker TR, Kugler JW, Goldberg RM, O'Connell MJ, Poon MA. 5-Fluorouracil–Based Chemotherapy for Advanced Colorectal Cancer in Elderly Patients: A North Central Cancer Treatment Group Study. Clin Colorectal Cancer 2005; 4:325-31. [PMID: 15663836 DOI: 10.3816/ccc.2005.n.005] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
Although 5-fluorouracil (5-FU)-based chemotherapy is commonly used in patients with advanced colorectal cancer (CRC), little data exist on the tolerability and benefit of therapy in elderly patients. To compare toxicity, dose intensity, response rate, time to tumor progression, and overall survival for older and younger patients, we conducted a pooled analysis of 1748 patients, divided into 4 quartile-based age groups, from 4 North Central Cancer Treatment Group trials testing 5-FU with or without leucovorin for advanced CRC. Patients aged > 65 years had modestly higher rates of severe toxicity (grade >/= 3) overall (53% vs. 46%) and higher rates of diarrhea (21% vs. 16%), stomatitis (17% vs. 13%), and infection (4% vs. 2%). Toxicity rates were similar between patients aged 66-70 years and patients aged > 70 years. The response rate did not differ by age group (2-sided; P = 0.90); it was significantly lower for patients with higher performance status scores (30% for score of 0/1; 17% for 2/3; 2-sided; P = 0.001). Performance status, not age, was predictive of time to tumor progression and overall survival. The older patients with CRC treated with 5-FU have modestly higher rates of severe toxicity, mainly diarrhea and stomatitis. Supportive measures to control diarrhea and stomatitis may be particularly important in elderly patients. Age alone should not be used to determine whether older patients are treated, because performance status is predictive of dose intensity, response rate, time to tumor progression, and overall survival.
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Affiliation(s)
- Stacy D'Andre
- University of California, Davis, Sacramento, CA, USA
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47
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Ghiringhelli F, Ladoire S, Manckoundia P, Chauffert B, Solary E, Besancenot JF, Pfitzenmeyer P. [Treatment of cancer and hematological malignancy in elderly people: oncogeriatrics as a discipline for the future (Part I): geriatric evaluation and management of solid tumors]. Rev Med Interne 2004; 26:216-25. [PMID: 15777583 DOI: 10.1016/j.revmed.2004.10.021] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2004] [Accepted: 10/06/2004] [Indexed: 11/29/2022]
Abstract
PURPOSE Fifty percent of cancer arise in people older than 65 year-old. Most clinical trials in cancer treatment are limited in patients younger than 65 year-old. We review literature describing particularity of cancer treatment in elderly patients. CURRENT KNOWLEDGE AND KEY POINTS Therapeutic decisions should be based on an estimation of the patient's life expectancy, and risks and benefits should be weighted up accordingly. Geriatric oncology is made of a geriatric evaluation of patient and of knowledge of clinical trial about elderly patients. FUTURE PROSPECTS AND PROJECTS We present in this issue the principle of geriatric evaluation and the results of recent clinical trial on elderly cancer patients.
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Affiliation(s)
- F Ghiringhelli
- Unité Inserm 517, faculté de médecine, 7, boulevard Jeanne-d'Arc, 21000 Dijon, France.
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48
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Almeida EPMD, Gutiérrez MGRD, Adami NP. Monitoramento e avaliação dos efeitos colaterais da quimioterapia em pacientes com câncer de cólon. Rev Lat Am Enfermagem 2004; 12:760-6. [PMID: 15717075 DOI: 10.1590/s0104-11692004000500009] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
Este estudo objetivou monitorar e avaliar a ocorrência e grau de intensidade da náusea, vômito e diarréia em pacientes com neoplasia de cólon, submetidos à quimioterapia ambulatorial, que receberam informações de enfermagem para o manejo desses sintomas. Fizeram parte do estudo 17 pacientes tratados com 5-Fluorouracil e baixas doses de ácido folínico, no Ambulatório de Quimioterapia de Adultos do Hospital São Paulo/Universidade Federal de São Paulo. Foram elaborados instrumentos para o registro da ocorrência e grau de intensidade desses sintomas e folhetos com informações sobre o seu manejo. As informações e o seguimento foram realizados pela enfermeira do setor, durante as consultas de enfermagem. Os resultados evidenciaram que a maioria dos pacientes (82,4%) apresentou pelo menos um dos sinais e sintomas estudados, entre o primeiro e o 21º dias do ciclo de tratamento. A náusea foi o sintoma mais freqüente (76,5%), com pico no 4º e 5º dias do ciclo, seguida da diarréia (70,5%), com pico no 7º dia e, por último o vômito (53,0%), com pico no 5º dia. Quanto ao grau de intensidade desses sintomas, a maioria dos pacientes situou-se no grau 1, estabelecido como aceitável para o estudo, indicando que as orientações de enfermagem e o acompanhamento contínuo contribuíram para a maior efetividade do manejo desses sintomas por parte dos pacientes.
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Labianca R, Beretta GD, Mosconi S, Milesi L. The role of uracil-tegafur (UFT) in elderly patients with colorectal cancer. Crit Rev Oncol Hematol 2004; 52:73-80. [PMID: 15363468 DOI: 10.1016/j.critrevonc.2004.06.001] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/16/2004] [Indexed: 11/23/2022] Open
Abstract
5-Fluorouracil (5-FU) administered in several schedules since its introduction in 1957 continues to be an integral part of standard first-line therapy for colorectal cancer. Continuous intravenous (i.v.) infusion appears to yield improved response rate and overall survival, with fewer adverse effects compared with i.v. bolus dosing. However, these protracted infusions require portable infusion pumps and central venous lines, which are associated with complications (i.e. increased risk of infection and clotting and/or dislodgement of the catheter, increased risk of venous thrombosis). Colorectal carcinoma is the second cause of death for tumour after lung cancer. About 70% of cases occur over 65 years and 50% or more affects people over 70. In clinical research age was a common exclusion criteria and little information is available about the efficacy, safety and toxicity of chemotherapy in elderly patients because few studies focused on the treatment of cancer in that part of population. The goal of this article is to review the literature concerning the treatment of elderly patients with UFT, an orally administered dihydropyrimidine dehydrogenase (DPD) inhibitory fluoropyrimidine.
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Affiliation(s)
- Roberto Labianca
- Unit of Medical Oncology, Ospedali Riuniti, Bergamo, Largo Barozzi, 1, Bergamo I-24128, Italy.
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50
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Minami H, Ohe Y, Niho S, Goto K, Ohmatsu H, Kubota K, Kakinuma R, Nishiwaki Y, Nokihara H, Sekine I, Saijo N, Hanada K, Ogata H. Comparison of pharmacokinetics and pharmacodynamics of docetaxel and Cisplatin in elderly and non-elderly patients: why is toxicity increased in elderly patients? J Clin Oncol 2004; 22:2901-8. [PMID: 15254059 DOI: 10.1200/jco.2004.10.163] [Citation(s) in RCA: 75] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023] Open
Abstract
PURPOSE Following phase I studies of docetaxel and cisplatin in patients with non-small-cell lung cancer, the recommended doses of docetaxel were different for elderly (> or = 75 years) and non-elderly (< 75 years) patients. To elucidate the mechanism of the difference, the pharmacokinetics of docetaxel and cisplatin were investigated in two phase II studies separately conducted in elderly and non-elderly patients. PATIENTS AND METHODS Twenty-seven elderly and 25 non-elderly patients were treated with three weekly administrations of docetaxel and cisplatin every 4 weeks. Doses of docetaxel were 20 and 35 mg/m(2) for elderly and non-elderly patients, respectively. All patients received 25 mg/m(2) of cisplatin. The pharmacokinetics and pharmacodynamics of docetaxel and cisplatin were compared in elderly and non-elderly patients. RESULTS There were no differences in pharmacokinetics of docetaxel or cisplatin between elderly versus non-elderly patients with regard to clearance and volume of distribution. In the pharmacodynamic analysis, neutropenia was positively correlated with the area under the concentration-time curve for docetaxel but not for cisplatin. In evaluating the relationship between neutropenia and the area under the concentration-time curve of docetaxel, elderly patients experienced greater neutropenia than those predicted by a pharmacodynamic model developed in non-elderly patients; the residual for prediction of the percent change in neutrophil count was -11.2% (95% CI, -21.8 to -0.5%). CONCLUSION The pharmacokinetics of docetaxel and unchanged cisplatin were not different between elderly and non-elderly patients. The elderly patients were more sensitive to docetaxel exposure than the non-elderly patients, resulting in the different recommended doses for the phase II studies.
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Affiliation(s)
- Hironobu Minami
- Division of Oncology/Hematology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa 277-8577, Japan.
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