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1
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Cortinovis D, Bajetta E, Di Bartolomeo M, Dognini G, Beretta E, Ferrario E, Ricotta R, Buzzoni R. Raltitrexed plus Oxaliplatin in the Treatment of Metastatic Colorectal Cancer. TUMORI JOURNAL 2018; 90:186-91. [PMID: 15237580 DOI: 10.1177/030089160409000205] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Aims and background As raltitrexed and oxaliplatin (L-OHP) are both effective in the treatment of colorectal cancer but have different mechanisms of action, we studied the antitumoral activity and safety of their combined use in patients with advanced colorectal cancer. Methods A 15-min intravenous infusion of raltitrexed (2.5 mg/m2) and a 180-min infusion of oxaliplatin (100 mg/m2) were administered on day 1 every three weeks for a maximum of six cycles. Results The study involved 51 patients (27 males and 24 females) with a median age of 65 years (range, 43-78); 28 were aged ≥65 years. The primary tumor site was the colon in 35 patients and the rectum in 16. Thirty-four patients had received prior chemotherapy: 20 as adjuvant treatment and 14 as pretreatment. The most frequent metastatic sites were liver (18 cases), lung (10 cases), liver + lung (8 cases) and lymph nodes (3 cases). Twenty-four patients completed the entire treatment plan. The most common toxicities were transaminitis (16 patients, grade 3-4), diarrhea (six patients, grade 3), nausea/vomiting (one patient, grade 4), and asthenia (one patient, grade 3). The treatment was stopped in one patient because of prolonged grade 4 transaminitis. The adverse event profile was similar in the patients aged >65 years and <65 years. Complete responses were observed in 2 patients, partial responses in 12, stable disease in 23, and progression in 8. Conclusions The results of the study suggest that the raltitrexed plus oxaliplatin regimen is feasible and clinically active in advanced colorectal cancer.
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Affiliation(s)
- Diego Cortinovis
- Medical Oncology Unit B, National Cancer Institute, Milan, Italy
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2
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Li M, Sun Q, Li S, Zhai Y, Wang J, Chen B, Lu J. Chronic restraint stress reduces carbon tetrachloride-induced liver fibrosis. Exp Ther Med 2016; 11:2147-2152. [PMID: 27284296 PMCID: PMC4887823 DOI: 10.3892/etm.2016.3205] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2015] [Accepted: 01/11/2016] [Indexed: 12/25/2022] Open
Abstract
Stress as a cofactor has been reported to affect the progression and severity of liver diseases. The present study investigated the effect of chronic restraint stress on carbon tetrachloride (CCl4)-induced liver fibrosis. A total of 30 male BALB/c mice were randomly divided into three groups: Oil-treated control group; CCl4-treated group; and CCl4 + restraint-treated group. CCl4 was administrated via intraperitoneal injection once every 3 days over a period of 42 days. In the CCl4 + restraint-treated group, mice were immobilized using 50 ml centrifuge tubes for 0.5 h to inflict chronic restraint stress immediately after the injection of CCl4. On day 42, blood and liver tissue samples were collected for analysis. The effect of restraint on CCl4-induced liver fibrosis in mice was evaluated by analyzing the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Histopathological examination of liver samples was performed using hematoxylin and eosin (HE), Masson's trichrome, 5-hydroxytryptamine 2B (5-HT2B) receptor and α-smooth muscle actin (α-SMA) immumohistochemical staining. ALT, AST, 5-HT2B receptor and α-SMA expression levels were significantly increased in mice exposed to CCl4 in comparison with those in the oil-treated control mice (P<0.01). However, these increases were significantly reduced by exposure to restraint (P<0.05). HE and Masson's trichrome staining revealed that restraint can alleviate CCl4-induced liver fibrosis. These results suggest that chronic restraint stress reduces the development of liver fibrosis by inhibiting the activation of hepatic stellate cells via 5-HT2B receptor. Therefore, restraint may be a useful therapeutic approach in the management of liver fibrosis.
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Affiliation(s)
- Meng Li
- Department of Laboratory Animal Science, School of Basic Medical Science, Capital Medical University, Beijing 100069, P.R. China
| | - Quan Sun
- Department of Laboratory Animal Science, School of Basic Medical Science, Capital Medical University, Beijing 100069, P.R. China
| | - Shengli Li
- Department of Laboratory Animal Science, School of Basic Medical Science, Capital Medical University, Beijing 100069, P.R. China
| | - Yanan Zhai
- Department of Laboratory Animal Science, School of Basic Medical Science, Capital Medical University, Beijing 100069, P.R. China
| | - Jingjing Wang
- Department of Laboratory Animal Science, School of Basic Medical Science, Capital Medical University, Beijing 100069, P.R. China
| | - Baian Chen
- Department of Laboratory Animal Science, School of Basic Medical Science, Capital Medical University, Beijing 100069, P.R. China
| | - Jing Lu
- Department of Laboratory Animal Science, School of Basic Medical Science, Capital Medical University, Beijing 100069, P.R. China
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Benavides M, Berciano-Guerrero M. Elderly patients with metastatic colorectal cancer: overall issues and first-line chemotherapy options. COLORECTAL CANCER 2013. [DOI: 10.2217/crc.13.69] [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 The aging phenomenon is resulting in an ever greater incidence of colorectal cancer (CRC) in the elderly. Chronologic age is not the best or only way to define elderly patients because aging varies greatly. Comprehensive geriatric assessment has proved beneficial for more appropriate therapeutic options although its influence on treatment decisions and outcomes remains to be validated. Fit elderly patients with metastatic CRC derive similar benefits to their younger counterparts, but only one Phase III trial exists to define the best treatment. New strategies such as maintenance therapies, which are particularly appropriate in these patients, are needed. As very few data are available for the vulnerable/frail elderly population, it is important to better define these terms and the efficacy (if any) of treatment modalities in this group. Translational research in geriatric oncology must be improved in this heterogeneous population to identify biological and clinical correlates of cancer and aging, ameliorating personalized treatment in elderly metastatic CRC patients.
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Affiliation(s)
- Manuel Benavides
- Medical Oncology Department, Hospital Regional Universitario Carlos Haya, Málaga, Spain
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4
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Göktaş C, Horuz R, Yıldırım M, Faydacı G, Sahin C, Albayrak S. [Major urologic surgical procedures in locally advanced colorectal cancers]. Actas Urol Esp 2012; 36:361-6. [PMID: 22266254 DOI: 10.1016/j.acuro.2011.09.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2011] [Accepted: 09/13/2011] [Indexed: 11/16/2022]
Abstract
OBJECTIVE To evaluate the outcomes of major urological procedures performed in patients with locally advanced colorectal cancer. MATERIAL AND METHODS Data of 37 patients with locally advanced colorectal cancer who underwent major urological surgical procedures along with simultaneous cancer surgery between the years of 2005 and 2010 were retrospectively evaluated. RESULTS The mean age was 58.3 years. Male/Female ratio was 2.7. 59% of the patients were primary, and 41% were recurrent cases of colorectal cancer. Bladder, ureters, urethra, kidneys and prostate were found as invaded in 19, 9, 5, 2 and 2 cases, respectively. The following single or combined procedures were performed; partial (n=11) or total (n=8; 2 combined with urethrocutaneostomy, 6 with ileal-conduit) cystectomy, urethroplasty (n=5), nephroureterectomy (n=2), radical nephrectomy (n=1), partial nephrectomy (n=1), ureteroneocystostomy (n=7), Boari's flap (n=4), transureteroureterostomy (n=3). Prolonged drainage was the most common surgical complication (27%). Urethrocutaneous fistula and total urinary incontinence were encountered in 1 and 1 patient, respectively. The incidence of hydronephrosis and elevated creatinine were 38% (preoperative 27%; postoperative 11%) and 24% (11% preoperative; 13% postoperative), respectively. Two deaths occurred in the first month of operations. Mean duration of follow up was 18(6-28) months for surviving 13 patients. Overall survival in 24 cases resulting in death was 21(1-42) months. CONCLUSIONS Since the most important eventual effects of locally advanced colorectal cancer are on the kidneys from the urological point of view; the aim of an urologist, as a member of surgical team, should be preserving renal function in addition to helping complete removal of the tumor.
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Affiliation(s)
- C Göktaş
- Clínica de Urología, Hospital de Formación Kartal, Estambul, Turquía
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5
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Sastre J, Grávalos C, Rivera F, Massuti B, Valladares-Ayerbes M, Marcuello E, Manzano JL, Benavides M, Hidalgo M, Díaz-Rubio E, Aranda E. First-line cetuximab plus capecitabine in elderly patients with advanced colorectal cancer: clinical outcome and subgroup analysis according to KRAS status from a Spanish TTD Group Study. Oncologist 2012; 17:339-45. [PMID: 22363067 DOI: 10.1634/theoncologist.2011-0406] [Citation(s) in RCA: 63] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
UNLABELLED Single-agent cetuximab is safe and active in elderly patients with advanced colorectal cancer (CRC). A cetuximab-capecitabine combination has not previously been tested in elderly patients with advanced CRC. MATERIAL AND METHODS Sixty-six patients with advanced CRC were treated with cetuximab as a 400 mg/m2 i.v. infusion followed by 250 mg/m2 i.v. weekly plus capecitabine at a dose of 1,250 mg/m2 every 12 hours. After the inclusion of 27 patients, the protocol was amended for safety reasons, reducing the dose of capecitabine to 1,000 mg/m2 every 12 hours. Thirty-nine additional patients were treated with the reduced dose of capecitabine. RESULTS The overall response rate was 31.8%. KRAS status was determined in 58 patients (88%). Fourteen of 29 patients with wild-type KRAS tumors responded (48.3%; 95% confidence interval [CI], 29.4%-67.5%), compared with six of 29 patients with mutant KRAS tumors (20.7%; 95% CI, 8.0%-39.7%). The median progression-free survival (PFS) interval was 7.1 months. The median PFS interval for patients whose tumors were wild-type KRAS was significantly longer than for those with mutant KRAS tumors (8.4 months versus 6.0 months; p = .024). The high incidence of severe paronychia (29.6%) declined (7.7%) after capecitabine dose adjustment. CONCLUSIONS Cetuximab plus capecitabine at a dose of 1,000 mg/m2 every 12 hours may be an alternative to more aggressive regimens in elderly patients with advanced wild-type KRAS CRC.
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Affiliation(s)
- Javier Sastre
- Medical Oncology Department, Hospital Clínico San Carlos, Calle Martín Lagos s/n 28040 Madrid, Spain.
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Sastre J, Aranda E, Grávalos C, Massutí B, Varella-Garcia M, Rivera F, Soler G, Carrato A, Manzano JL, Díaz-Rubio E, Hidalgo M. First-line single-agent cetuximab in elderly patients with metastatic colorectal cancer. A phase II clinical and molecular study of the Spanish group for digestive tumor therapy (TTD). Crit Rev Oncol Hematol 2009; 77:78-84. [PMID: 20042346 DOI: 10.1016/j.critrevonc.2009.11.005] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2009] [Revised: 11/10/2009] [Accepted: 11/26/2009] [Indexed: 12/11/2022] Open
Abstract
PURPOSE to evaluate the efficacy and safety of first-line single-agent cetuximab in fit elderly patients with metastatic colorectal cancer, as well as potential molecular predictive factors for efficacy. PATIENTS AND METHODS patients aged 70 or older with metastatic CRC without criteria for frailty and no prior treatment for advanced disease were treated with single-agent cetuximab 400mg/m(2) followed by weekly 250mg/m(2) until disease progression or unacceptable toxicity. RESULTS forty-one patients were included. Two patients achieved a complete response and 4 patients had a partial response for an overall response rate of 14.6%. Fifteen patients (36.6%) remained stable. Median time to progression was 2.9 months and median overall survival 11.1 months despite two-third of patients received chemotherapy at progression. Forty-five percent of EGFR gene copy number positive patients by FISH were progression-free at 12 weeks, in contrast with 12% of FISH negative patients (p=0.04). Grade 3 skin toxicity was reported in 5 patients (12.2%). Hypersensitivity infusion reactions were not reported and there were no toxic deaths. CONCLUSION cetuximab is a safe monoclonal antibody with moderate activity in first-line metastatic colorectal cancer, but the present study does not support the use of cetuximab as single-agent in first-line fit elderly patients with metastatic CRC.
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Affiliation(s)
- J Sastre
- HC San Carlos, Madrid, Center affíliated to the Red Temática de Investigación Cooperativa (RD06/0020/0021), Instituto Carlos III, Spanish Ministry of Science and Innovation, Spain.
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Feliu J, Sereno M, Castro JD, Belda C, Casado E, González-Barón M. Chemotherapy for colorectal cancer in the elderly: Whom to treat and what to use. Cancer Treat Rev 2009; 35:246-54. [PMID: 19345021 DOI: 10.1016/j.ctrv.2008.11.004] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2008] [Revised: 11/13/2008] [Accepted: 11/17/2008] [Indexed: 12/27/2022]
Abstract
The median age at diagnosis of colorectal cancer is during the seventh decade, and the incidence of the disease increases continuously with age. However, as the age increases, the possibilities of receiving adequate cancer treatment diminish and the mortality rises. So, there is a huge need for defined treatment strategies in elderly patients with colorectal carcinoma. The geriatric population is a very heterogeneous group where patients with an excellent health status coexist with the patients with both co-morbidities and functional dependency. Therefore, it is necessary to personalize each treatment according to the degree of vulnerability of the elderly patients. It is essential to set up a multidimensional geriatric assessment in order to consider not only the stage of the disease, but also all the factors that may influence the survival and interfere with the treatment. The aim of this review is to discuss the potential benefits and issues of chemotherapy in the elderly patients affected with colorectal cancer.
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Affiliation(s)
- Jaime Feliu
- Medical Oncology Department, La Paz Hospital, Madrid, Spain
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8
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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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Predictive factors for chemotherapy-related toxic effects in patients with colorectal cancer. ACTA ACUST UNITED AC 2008; 5:455-65. [DOI: 10.1038/ncponc1137] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2007] [Accepted: 03/26/2008] [Indexed: 01/25/2023]
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10
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Figer A, Perez-Staub N, Carola E, Tournigand C, Lledo G, Flesch M, Barcelo R, Cervantes A, André T, Colin P, Louvet C, de Gramont A. FOLFOX in patients aged between 76 and 80 years with metastatic colorectal cancer: an exploratory cohort of the OPTIMOX1 study. Cancer 2007; 110:2666-71. [PMID: 17963264 DOI: 10.1002/cncr.23091] [Citation(s) in RCA: 72] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
BACKGROUND Patients older than 75 years of age are usually excluded from metastatic colorectal cancer randomized studies. The OPTIMOX1 study evaluated FOLFOX7, a simplified (s) leucovorin (LV) and 5-fluorouracil (5FU) regimen (sLV5FU2) with high-dose oxaliplatin, in a new oxaliplatin stop-and-go strategy. An exploratory cohort of patients aged 76 to 80 years was included in the study. METHODS In all, 620 previously untreated patients were randomized between FOLFOX4 until progression (arm A), or FOLFOX7 for 6 cycles, maintenance without oxaliplatin for 12 cycles, and reintroduction of FOLFOX7 (arm B). RESULTS A total of 37 patients aged 76 to 80 years were included, 20 in arm A and 17 in arm B. The overall response rate (ORR) was 59.4%, comparable to younger patients (59%). Median progression-free survival (PFS) was 9.0 months and median overall survival (OS) was 20.7 months. These results did not differ from that in younger patients < or =75 years in the OPTIMOX1 study with PFS 9.0 months (P = .63) and OS 20.2 months (P = .57). They experienced slightly more grade 3 of 4 toxicity than younger patients: 65% versus 48% (P = .06), mainly with more neutropenia (41% vs 24%, P = .03) and neurotoxicity (22% vs 11%, P = .06). Tolerability, however, was manageable and no toxic death occurred in this elderly population. CONCLUSIONS The efficacy of FOLFOX-based treatment was maintained in patients >75 years with both FOLFOX regimens. The oxaliplatin stop-and-go management strategy performed well in this population.
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Affiliation(s)
- Arié Figer
- Beth Sourasky Medical Center Tel Aviv, Israel
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Abstract
Although hepatotoxicity is a frequent concern with all medications, chemotherapeutic agents are more often implicated in causing liver damage than most other drug classes. In many instances, these reactions are considered dose related because cytotoxic therapy directed at rapidly growing cancer cells may readily impact hepatocytes even though they are dividing more slowly. Because the stakes (remission of cancer) are high, so are the risks that the oncologist and the patient are willing to assume. The dose of many chemotherapeutic agents is limited by the toxic effects on the lungs, bone marrow, kidneys, and gastrointestinal system, including the liver. An awareness of the toxic potential of each chemotherapeutic agent is necessary before initiation of new oncologic treatments.
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Affiliation(s)
- Edmundo A Rodriguez-Frias
- Department of Internal Medicine, The University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA
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Cao S, Bhattacharya A, Durrani FA, Fakih M. Irinotecan, oxaliplatin and raltitrexed for the treatment of advanced colorectal cancer. Expert Opin Pharmacother 2006; 7:687-703. [PMID: 16556086 DOI: 10.1517/14656566.7.6.687] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
Out of every 17-18 individuals in the US, one develops colorectal cancer (CRC) in their lifetime. Of individuals diagnosed with CRC, > 50% present or develop metastatic disease, which, if untreated, is associated with 6-9 months median survival. Although surgical resection is the primary treatment modality for CRC, chemotherapy is the mainstay of treatment for metastatic or unresectable disease. For nearly three decades, 5-fluorouracil (5-FU) has been the chemotherapy of choice for treatment of CRC. However, the response rates to single 5-FU therapy have been suboptimal with an objective tumour response of 10-20%. Attempts have been made to improve the efficacy of 5-FU by either schedule alteration (protracted infusion versus intravenous push) or biochemical modulation with leucovorin (LV). Continuous infusion induced more tumour regression and prolonged the time-to-disease progression with some significant impact on survival (11.3 versus 12.1 months; p < 0.04). 5-FU/LV resulted in a significant increase in overall response rates and in the prolongation of disease-free survival in the adjuvant setting, although severe toxicities represent a major clinical problem. The last 10 years have seen the addition of several new agents such as irinotecan, oxaliplatin, raltitrexed, bevacizumab and cetuximab. The prognosis has significantly improved with the addition of these agents, with median survivals now > 20 months. This review paper focuses on irinotecan, oxaliplatin and raltitrexed when used alone and in combination.
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Affiliation(s)
- Shousong Cao
- Department of Pharmacology & Therapeutics, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
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13
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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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14
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Gebbia V, Verderame F, Ferraù F, Bordonaro R, Callari A, Caruso M, Tirrito ML, Valenza R, Cicero G, Borsellino N, Tralongo P. Raltitrexed plus levofolinic acid and bolus/continuous infusion 5-fluorouracil on a biweekly schedule for elderly patients with advanced colorectal carcinomas. Ann Oncol 2006; 17 Suppl 7:vii60-vii65. [PMID: 16760296 DOI: 10.1093/annonc/mdl953] [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: 12/13/2022] Open
Abstract
BACKGROUND The aim of the study was to evaluate the safety and efficacy of the raltitrexed/5-fluorouracil/levofolinic acid combination regimen as first-line chemotherapy for elderly patients with advanced/metastatic colorectal cancer. PATIENTS AND METHODS Previously untreated patients with metastatic colorectal cancer received raltitrexed 2 mg/m(2) i.v. plus levofolinic acid and 5-fluorouracil according to the De Gramont' schedule given every 2 weeks as first-line chemotherapy. Patients were re-evaluated after six cycles and chemotherapy was continued up to tolerance or disease progression. RESULTS Seventy patients aged >/=65 years were accrued from 11 centers between September 2001 and July 2002. According to the intention-to-treat analysis, the overall response rate was 35% (95% CI 29.5% to 40.5%) including one complete response (1%) and 24 partial responses (34%). Twenty patients (31%) showed a stabilization of disease for a tumor growth control rate of 64% (95% CI 57% to 71%). The median overall survival was 12.5 months and the median time to disease progression was 6.5 months. No toxic deaths or allergic reaction were recorded. Grade 4 toxicities were non-existent. The main hematological toxicity was grade 3 neutropenia, which occurred in 9% of patients, and grade 3 anemia in only one case, while no case of graded 3 thrombocytopenia was observed. Grade 3 non-hematological toxicities were asthenia (11%), transient increase of transaminases (10%) and diarrhea (4%). CONCLUSIONS The results of this study suggest that the raltitrexed/5-fluorouracil/levolofinic acid combination is an effective and well tolerated regimen for the treatment of elderly patients with advanced colorectal cancer. Its ease of administration and patient's tolerance warrant further investigation over 5-fluorouracil/folinic acid regimens.
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Affiliation(s)
- V Gebbia
- Medical Oncology Units of the: Department of Experimental Oncology and Clinical Applications, University of Palermo, Italy.
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15
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González Barón M, Espinosa E. Oncopaz cooperative group. Clin Transl Oncol 2006; 8:145-7. [PMID: 16648112 DOI: 10.1007/s12094-006-0003-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
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Scagliotti GV, Selvaggi G. Antimetabolites and cancer: emerging data with a focus on antifolates. Expert Opin Ther Pat 2006; 16:189-200. [DOI: 10.1517/13543776.16.2.189] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
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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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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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Aparicio J, Vicent JM, Maestu I, Bosch C, Galán A, Busquier I, Llorca C, Garcerá S, Campos JM, López-Tendero P, Balcells M. First-Line Treatment with Irinotecan and Raltitrexed in Metastatic Colorectal Cancer. Oncology 2005; 68:58-63. [PMID: 15809521 DOI: 10.1159/000084821] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2004] [Accepted: 08/08/2004] [Indexed: 11/19/2022]
Abstract
OBJECTIVES The combination of irinotecan and raltitrexed is safe and active in 5-fluorouracil-refractory, metastatic colorectal cancer (CRC), with the advantage of its convenient three-weekly schedule. The aim of this multicenter phase II study was to assess its efficacy and toxicity in first-line treatment. METHODS Between May 2000 and March 2001, 62 previously untreated patients received irinotecan (350 mg/m(2)) plus raltitrexed (3 mg/m(2)), with courses repeated every 21 days. Objective response was assessed every three courses, and treatment maintained until tumor progression or unacceptable toxicity. RESULTS A total of 331 cycles were administered, with a median of five cycles per patient (range, 1-16). Seventeen patients achieved a partial response and 2 a complete response, for an overall intention-to-treat response rate of 30% (95% confidence interval, 18-44%). The incidence of grade 3-4 toxicity per patient was diarrhea (27%), emesis (13%), anemia (12%), neutropenia (9%), and asthenia (7%). Three patients (5%) died from treatment-related adverse events (diarrhea plus neutropenia). The median potential follow-up is now 37 months. Median survival was 12.2 months, and median time to progression was 6.3 months. CONCLUSIONS The combination of irinotecan plus raltitrexed is an easy comfortable schedule for patients with metastatic CRC, but both efficacy and toxicity results seem suboptimal for first-line treatment.
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Affiliation(s)
- Jorge Aparicio
- Medical Oncology Department of Hospital Universitario La Fe, ES-46009 Valencia, Spain.
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Aparicio T, Desramé J, Lecomte T, Mitry E, Belloc J, Etienney I, Montembault S, Vayre L, Locher C, Ezenfis J, Artru P, Mabro M, Dominguez S. Oxaliplatin- or irinotecan-based chemotherapy for metastatic colorectal cancer in the elderly. Br J Cancer 2003; 89:1439-44. [PMID: 14562014 PMCID: PMC2394343 DOI: 10.1038/sj.bjc.6601310] [Citation(s) in RCA: 67] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
The tolerance and efficacy of oxaliplatin and irinotecan for metastatic colorectal cancer are unknown in elderly patients. Methods. All consecutive patients over 74 years treated with oxaliplatin or irinotecan for metastatic colorectal cancer were enrolled. The tumour response was assessed every 2–3 months and toxicity was collected at each cycle according to World Health Organisation criteria. A total of 66 patients were enrolled from 12 centres. The median age was 78 years (range, 75–88 years); 39 patients had no severe comorbidity according to the Charlson score. In total, 44 and 22 patients received oxaliplatin or irinotecan, respectively, in combination with 5-fluororuracil±folinic acid or raltitrexed in 64 patients. A total of 545 chemotherapy cycles were administered in first (41%), second (51%) or third line (8%). A dose reduction occurred in 190 cycles (35%). Complete response, partial response and stabilisation occurred in 1.5, 20 and 47% of patients, respectively. The median time to progression and overall survival were 6.8 and 11.2 months in first line and 6.3 and 11.6 months in second line, respectively. Grade 3 and 4 toxicity occurred in 42% of patients: neutropenia 17%, diarrhoea 15%, neuropathy 11%, nausea and vomiting 8% and thrombopenia 6%. There was no treatment-related death. In selected elderly patients, chemotherapy with oxaliplatin or irinotecan is feasible with manageable toxicity.
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Affiliation(s)
- T Aparicio
- Service d'Hépato-Gastroentérologie, Hôpital Bichat-Claude Bernard, 46 rue Henri Huchard, AP-HP, Paris 75018, France.
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Abstract
AIM: To analyse the prognostic factors in 165 colorectal patients aged ≥ 70.
METHODS: One hundred and sixty-five elderly patients with colorectal cancer diagnosed by histology were entered into the retrospective study between 1994 and 2001. Patients were given optimal operation alone, chemotherapy after operation, or chemotherapy alone according to tumor stage, histology, physical strength, and co-morbid problems. Survival rate was calculated by Kaplan-Meier method, and compared with meaningful variances by Log-rank method. Prognostic factors were analyzed by Cox regression.
RESULTS: The 1, 2, 3, 4, 5 year survival rate (all-cause mortality) was 87.76%, 65.96%, 52.05%, 42.77%, 40.51%, respectively. The mean survival time was 41.89 ± 2.33 months (95%CI: 37.33-46.45 months), and the median survival time was 37 months. Univariate analysis showed that factors such as age, nodal metastasis, treatment method, Duke’s stage, gross findings, kind of histology, and degree of differentiation had influences on the survival rate. Multivariate analysis showed that factors such as treatment method, Duke’s stage, kind of histology and degree of differentiation were independent prognostic factors.
CONCLUSION: This study suggests that the prognosis of elderly colorectal cancer patients is influenced by several factors. Most of elderly patients can endure surgery and/or chemotherapy, and have a long-time survival and good quality of life.
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Affiliation(s)
- Ke-Jun Nan
- Department of Oncology, First Hospital of Xi'an Jiaotong University, 1 Jiankang Xilu, Xi'an 710061, Shaanxi Province, China
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Hoff PMG. New drugs for colorectal cancer. CANCER CHEMOTHERAPY AND BIOLOGICAL RESPONSE MODIFIERS 2003; 21:817-29. [PMID: 15338776 DOI: 10.1016/s0921-4410(03)21039-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/30/2023]
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