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Zhu S, Yu Y, Yang M, Liu X, Lai M, Zhong J, Zhao X, Lu L, Liu Y. Hepatic artery infusion chemotherapy combined with the FOLFOX regimen for the treatment of hepatocellular carcinoma: recent advances and literature review. Expert Rev Anticancer Ther 2024; 24:423-434. [PMID: 38651280 DOI: 10.1080/14737140.2024.2346624] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2024] [Accepted: 04/19/2024] [Indexed: 04/25/2024]
Abstract
INTRODUCTION The incidence of primary liver cancer (PLC) has experienced a significant global increase, primarily attributed to the rise in hepatocellular carcinoma (HCC). Unfortunately, HCC is often diagnosed in advanced stages, leaving patients with limited treatment options. Therefore, transformation therapy is a crucial approach for long-term survival and radical resection in patients with advanced HCC. Conversion therapy has demonstrated promise in the treatment of advanced HCC. When integrated with the FOLFOX regimen, hepatic artery infusion chemotherapy (HAIC) can significantly improve tumor response efficiency, leading to high conversion and resection rates. AREAS COVERED We reviewed landmark trials of HAIC in combination with different drugs or means for the treatment of HCC to determine the clinical value of HAIC-centric translational therapies in HCC treatment. Furthermore, we specifically emphasize the advantages associated with employing FOLFOX-HAIC in the treatment of advanced HCC. EXPERT OPINION The combination of HAIC with the FOLFOX regimen can help prevent the low intratumoral accumulation and high adverse reaction rate caused by the FOLFOX alone, holding significant potential in the comprehensive treatment of future HCC patients.
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Affiliation(s)
- Suqi Zhu
- Zhuhai Interventional Medical Center, Zhuhai Clinical Medical College of Jinan University (Zhuhai People's Hospital), Zhuhai, Guangdong, China
| | - Yahan Yu
- Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine, Zhuhai Clinical Medical College of Jinan University (Zhuhai People's Hospital), Zhuhai, Guangdong, China
| | - Mingqi Yang
- Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine, Zhuhai Clinical Medical College of Jinan University (Zhuhai People's Hospital), Zhuhai, Guangdong, China
| | - Xin Liu
- Zhuhai Precision Medical Center, Zhuhai Clinical Medical College of Jinan University (Zhuhai People's Hospital), Zhuhai, Guangdong, China
| | - Mingkai Lai
- Zhuhai Interventional Medical Center, Zhuhai Clinical Medical College of Jinan University (Zhuhai People's Hospital), Zhuhai, Guangdong, China
| | - Jieren Zhong
- Zhuhai Interventional Medical Center, Zhuhai Clinical Medical College of Jinan University (Zhuhai People's Hospital), Zhuhai, Guangdong, China
| | - Xiaoguang Zhao
- Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine, Zhuhai Clinical Medical College of Jinan University (Zhuhai People's Hospital), Zhuhai, Guangdong, China
| | - Ligong Lu
- Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine, Zhuhai Clinical Medical College of Jinan University (Zhuhai People's Hospital), Zhuhai, Guangdong, China
| | - Yanyan Liu
- Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine, Zhuhai Clinical Medical College of Jinan University (Zhuhai People's Hospital), Zhuhai, Guangdong, China
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Torres-Jiménez J, Esteban-Villarrubia J, Ferreiro-Monteagudo R, Carrato A. Local Treatments in the Unresectable Patient with Colorectal Cancer Metastasis: A Review from the Point of View of the Medical Oncologist. Cancers (Basel) 2021; 13:5938. [PMID: 34885047 PMCID: PMC8656541 DOI: 10.3390/cancers13235938] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2021] [Revised: 11/18/2021] [Accepted: 11/21/2021] [Indexed: 12/12/2022] Open
Abstract
For patients with isolated liver metastases from colorectal cancer who are not candidates for potentially curative resections, non-surgical local treatments may be useful. Non-surgical local treatments are classified according to how the treatment is administered. Local treatments are applied directly on hepatic parenchyma, such as radiofrequency, microwave hyperthermia and cryotherapy. Locoregional therapies are delivered through the hepatic artery, such as chemoinfusion, chemoembolization or selective internal radiation with Yttrium 90 radioembolization. The purpose of this review is to describe the different interventional therapies that are available for these patients in routine clinical practice, the most important clinical trials that have tried to demonstrate the effectiveness of each therapy and recommendations from principal medical oncologic societies.
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Affiliation(s)
- Javier Torres-Jiménez
- Medical Oncology Department, University Hospital Ramon y Cajal, 28034 Madrid, Spain; (J.E.-V.); (R.F.-M.)
| | - Jorge Esteban-Villarrubia
- Medical Oncology Department, University Hospital Ramon y Cajal, 28034 Madrid, Spain; (J.E.-V.); (R.F.-M.)
| | - Reyes Ferreiro-Monteagudo
- Medical Oncology Department, University Hospital Ramon y Cajal, 28034 Madrid, Spain; (J.E.-V.); (R.F.-M.)
| | - Alfredo Carrato
- Medical Oncology Department, Ramón y Cajal Health Research Institute (IRYCIS), CIBERONC, Alcalá University, University Hospital Ramon y Cajal, 28034 Madrid, Spain;
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Fountzilas E, Krishnan E, Janku F, Fu S, Karp DD, Naing A, Subbiah V, Hong DS, Piha-Paul SA, Vining DJ, Tsimberidou AM. A phase I clinical trial of hepatic arterial infusion of oxaliplatin and oral capecitabine, with or without intravenous bevacizumab, in patients with advanced cancer and predominant liver involvement. Cancer Chemother Pharmacol 2018; 82:877-885. [PMID: 30182147 DOI: 10.1007/s00280-018-3680-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2018] [Accepted: 08/27/2018] [Indexed: 01/25/2023]
Abstract
BACKGROUND We investigated hepatic arterial infusion (HAI) oxaliplatin combined with capecitabine +/- bevacizumab in advanced cancer with predominant liver involvement. METHODS Patients received HAI oxaliplatin (140 mg/m2) and escalating doses of capecitabine (500, 750, and 1000 mg/m2), with (Group 1) or without (Group 2) bevacizumab (10 mg/kg IV). A 3 + 3 dose design was used, followed by an expansion phase. RESULTS From 9/2009 to 2/2014, 61 patients (34 men, 27 women) were enrolled (Group 1 = 44; Group 2 = 17). Patients were treated in Group 2 if they had contraindications to bevacizumab (n = 13) or if there was no opening in Group 1 (n = 4). The median age was 60 years (range, 20-88). The most common cancers were colorectal (22 patients), liver (12), pancreatic (7), breast (4), and biliary tract (4). The median number of prior therapies was 3 (range, 1-12); 32 (53%) patients had received oxaliplatin. The dose-limiting toxicity was Grade 3 diarrhea and occurred in 2 patients receiving 1000 mg/m2 capecitabine. The maximum tolerated dose was HAI oxaliplatin 140 mg/m2, capecitabine 750 mg/m2, and bevacizumab 10 mg/kg. The most common toxicities were nausea/vomiting, anemia, thrombocytopenia, neutropenia, and hypomagnesemia. The rates of partial response and stable disease ≥ 4 months were 22% and 39% (Group 1) and 9% and 0% (Group 2). The respective median time to treatment failure and overall survival were 3 and 6.9 months (Group 1) and 1.5 and 5.9 months (Group 2). CONCLUSION HAI oxaliplatin combined with capecitabine +/- bevacizumab was well-tolerated and was associated with favorable outcomes in selected patients.
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Affiliation(s)
- Elena Fountzilas
- Department of Investigational Cancer Therapeutics, Unit 455, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA
| | - Elangovan Krishnan
- Department of Investigational Cancer Therapeutics, Unit 455, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA
| | - Filip Janku
- Department of Investigational Cancer Therapeutics, Unit 455, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA
| | - Siqing Fu
- Department of Investigational Cancer Therapeutics, Unit 455, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA
| | - Daniel D Karp
- Department of Investigational Cancer Therapeutics, Unit 455, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA
| | - Aung Naing
- Department of Investigational Cancer Therapeutics, Unit 455, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA
| | - Vivek Subbiah
- Department of Investigational Cancer Therapeutics, Unit 455, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA
| | - David S Hong
- Department of Investigational Cancer Therapeutics, Unit 455, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA
| | - Sarina A Piha-Paul
- Department of Investigational Cancer Therapeutics, Unit 455, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA
| | - David J Vining
- Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Apostolia-Maria Tsimberidou
- Department of Investigational Cancer Therapeutics, Unit 455, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA.
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Currie BM, Soulen MC. Decision Making: Intra-arterial Therapies for Cholangiocarcinoma-TACE and TARE. Semin Intervent Radiol 2017; 34:92-100. [PMID: 28579676 DOI: 10.1055/s-0037-1602591] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The incidence of intrahepatic cholangiocarcinoma (ICC) has been increasing in recent years and now represents the second most common primary hepatic cancer in the United States. The prognosis is dismal without surgical resection. In patients ineligible to receive curative treatments, locoregional therapies represent a diverse array of techniques that can stabilize or reverse tumor progression to improve overall survival and reduce tumor-related symptoms. Transarterial chemoembolization (TACE) and transarterial radioembolization (TARE) have been demonstrated to be efficacious methods for this patient population. Deciding between these two options is challenging. This article reviews the differences in patient selection, preprocedural evaluation, financial considerations and availability, quality of life, and rates of complications and overall survival.
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Affiliation(s)
- Brian M Currie
- Department of Radiology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania
| | - Michael C Soulen
- Department of Radiology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania
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Siqing F, Culotta KS, Falchook GS, Hong DS, Myers AL, Zhang YP, Naing A, Janku F, Hou MM, Kurzrock R. Pharmacokinetic evaluation of nanoparticle albumin-bound paclitaxel delivered via hepatic arterial infusion in patients with predominantly hepatic metastases. Cancer Chemother Pharmacol 2015; 77:357-64. [DOI: 10.1007/s00280-015-2946-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2015] [Accepted: 12/11/2015] [Indexed: 11/29/2022]
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A Case Report of Long-Term Survival following Hepatic Arterial Infusion of L-Folinic Acid Modulated 5-Fluorouracil Combined with Intravenous Irinotecan and Cetuximab Followed by Hepatectomy in a Patient with Initially Unresectable Colorectal Liver Metastases. Case Rep Oncol Med 2015; 2015:472037. [PMID: 26064730 PMCID: PMC4438152 DOI: 10.1155/2015/472037] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2015] [Accepted: 04/22/2015] [Indexed: 11/21/2022] Open
Abstract
A 43-year-old women admitted to our hospital for weight loss, anorexia, and abdominal pain was diagnosed with sigmoid neoplasm and multiple bilobar liver metastases. This patient received six cycles of systemic FOLFOX prior to a laparoscopically assisted anterior resection of the rectosigmoid for a poorly differentiated invasive adenocarcinoma T2N2M1, K-RAS negative (wild type). Hepatic arterial infusion (HAI) of L-folinic acid modulated 5-fluorouracil (LV/5-FU) with intravenous (iv) irinotecan (FOLFIRI) and cetuximab as adjuvant therapy resulted in a complete metabolic response (CR) with CEA normalization. A right hepatectomy extended to segment IV was performed resulting in (FDG-)PET negative remission for 7 months. Solitary intrahepatic recurrence was effectively managed by local radiofrequent ablation following 6c FOLFIRI plus cetuximab iv. Multiple lung lesions and recurrence of pulmonary and local lymph node metastases were successfully treated with fractionated stereotactic radiotherapy (50 Gy) and iv LV/5-FU/oxaliplatin (FOLFOX) plus cetuximab finally switched to panitumumab with CR as a result. At present the patient is in persistent complete remission of her stage IV colorectal cancer, more than 5 years after initial diagnosis of the advanced disease. Multidisciplinary treatment with HAI of chemotherapy (LV/5-FU + CPT-11) plus EGFR-inhibitor can achieve CR of complex unresectable LM and can even result in hepatectomy with possible long-term survival.
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Dose-finding study of hepatic arterial infusion of irinotecan-based treatment in patients with advanced cancers metastatic to the liver. Invest New Drugs 2015; 33:911-20. [PMID: 25990659 DOI: 10.1007/s10637-015-0251-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2015] [Accepted: 05/10/2015] [Indexed: 01/21/2023]
Abstract
BACKGROUND Liver metastases are associated with a poor prognosis. We investigated the use of hepatic arterial infusion (HAI) of irinotecan combination therapy in patients with liver metastases. PATIENTS AND METHODS Patients with histologically confirmed advanced cancer with liver metastases that was refractory to standard therapy were eligible. A standard "3 + 3" phase I study design was used to determine the dose-limiting toxicity (DLT) and the maximum tolerated dose (MTD). Three cohorts were evaluated: HAI of irinotecan with systemic intravenous (IV) (a) bevacizumab, (b) oxaliplatin and bevacizumab, or (c) bevacizumab and cetuximab. RESULTS From October 2009 through December 2013, 98 patients with various tumor types were enrolled (median age, 62 years, range, 34-85; and median number of prior therapies, 4, range, 1-11). In cohorts A and C, dose escalation continued until the highest dose level-considered the MTD-was reached. In cohort B, dose escalation continued until dose level 3, and dose level 2 was considered the MTD. Rates of grade 3/4 adverse events were as follows: diarrhea, 8 %; fatigue, 4 %; neutropenia, 4 %; thrombocytopenia, 2 %; and skin rash, 2 %. Seventy-seven patients were evaluable for response. Partial response was noted in 5 (6.5 %) patients (neuroendocrine cancer, n = 2; CRC, n = 2; NSCLC, n = 1); and stable disease ≥ 6 months in 17 (22.1 %) patients (CRC, n = 13; breast, n = 1; neuroendocrine, n = 1; NSCLC, n = 1; pancreatic, n = 1). CONCLUSIONS HAI irinotecan in combination with bevacizumab; oxaliplatin plus bevacizumab; or cetuximab plus bevacizumab was safe and may be a treatment option for selected patients with advanced cancer and liver involvement.
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Nosher JL, Ahmed I, Patel AN, Gendel V, Murillo PG, Moss R, Jabbour SK. Non-operative therapies for colorectal liver metastases. J Gastrointest Oncol 2015; 6:224-40. [PMID: 25830041 DOI: 10.3978/j.issn.2078-6891.2014.065] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2014] [Accepted: 07/20/2014] [Indexed: 12/16/2022] Open
Abstract
Locoregional therapies for colorectal liver metastases complement systemic therapy by providing an opportunity for local control of hepatic spread. The armamentarium for liver-directed therapy includes ablative therapies, embolization, and stereotactic body radiation therapy. At this time, prospective studies comparing these modalities are limited and decision-making relies on a multidisciplinary approach for optimal patient management. Herein, we describe multiple therapeutic non-surgical procedures and an overview of the results of these treatments.
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Affiliation(s)
- John L Nosher
- 1 Department of Radiology, Rutgers-Robert Wood Johnson Medical School, New Bruswick, NJ, USA ; 2 Department of Radiation Oncology, 3 Division of Medical Oncology, Robert Wood Johnson Medical School, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903, USA
| | - Inaya Ahmed
- 1 Department of Radiology, Rutgers-Robert Wood Johnson Medical School, New Bruswick, NJ, USA ; 2 Department of Radiation Oncology, 3 Division of Medical Oncology, Robert Wood Johnson Medical School, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903, USA
| | - Akshar N Patel
- 1 Department of Radiology, Rutgers-Robert Wood Johnson Medical School, New Bruswick, NJ, USA ; 2 Department of Radiation Oncology, 3 Division of Medical Oncology, Robert Wood Johnson Medical School, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903, USA
| | - Vyacheslav Gendel
- 1 Department of Radiology, Rutgers-Robert Wood Johnson Medical School, New Bruswick, NJ, USA ; 2 Department of Radiation Oncology, 3 Division of Medical Oncology, Robert Wood Johnson Medical School, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903, USA
| | - Philip G Murillo
- 1 Department of Radiology, Rutgers-Robert Wood Johnson Medical School, New Bruswick, NJ, USA ; 2 Department of Radiation Oncology, 3 Division of Medical Oncology, Robert Wood Johnson Medical School, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903, USA
| | - Rebecca Moss
- 1 Department of Radiology, Rutgers-Robert Wood Johnson Medical School, New Bruswick, NJ, USA ; 2 Department of Radiation Oncology, 3 Division of Medical Oncology, Robert Wood Johnson Medical School, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903, USA
| | - Salma K Jabbour
- 1 Department of Radiology, Rutgers-Robert Wood Johnson Medical School, New Bruswick, NJ, USA ; 2 Department of Radiation Oncology, 3 Division of Medical Oncology, Robert Wood Johnson Medical School, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903, USA
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Raval M, Bande D, Pillai AK, Blaszkowsky LS, Ganguli S, Beg MS, Kalva SP. Yttrium-90 radioembolization of hepatic metastases from colorectal cancer. Front Oncol 2014; 4:120. [PMID: 25120951 PMCID: PMC4110696 DOI: 10.3389/fonc.2014.00120] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2014] [Accepted: 05/09/2014] [Indexed: 12/29/2022] Open
Abstract
Liver metastases from colorectal cancer (CRC) result in substantial morbidity and mortality. The primary treatment is systemic chemotherapy, and in selected patients, surgical resection; however, for patients who are not surgical candidates and/or fail systemic chemotherapy, liver-directed therapies are increasingly being utilized. Yttrium-90 (Y-90) microsphere therapy, also known as selective internal radiation therapy (SIRT) or radioembolization, has proven to be effective in terms of extending time to progression of disease and also providing survival benefit. This review focuses on the use of Y-90 microsphere therapy in the treatment of liver metastases from CRC, including a comprehensive review of published clinical trials and prospective studies conducted thus far. We review the methodology, outcomes, and side effects of Y-90 microsphere therapy for metastatic CRC.
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Affiliation(s)
- Mihir Raval
- Department of Hospital Medicine, Essentia Health , Fargo, ND , USA
| | - Dinesh Bande
- Department of Hospital Medicine, Sanford Health , Fargo, ND , USA ; Roger Maris Cancer Center , Fargo, ND , USA ; Department of Internal Medicine, University of North Dakota , Fargo, ND , USA
| | - Anil K Pillai
- Harold Simmons Cancer Center, University of Texas Southwestern Medical Center , Dallas, TX , USA ; Interventional Radiology, University of Texas Southwestern Medical Center , Dallas, TX , USA
| | - Lawrence S Blaszkowsky
- Massachusetts General Hospital Cancer Center , Boston, MA , USA ; Department of Hematology and Oncology, Massachusetts General Hospital , Boston, MA , USA ; Department of Medicine, Harvard Medical School , Boston, MA , USA
| | - Suvranu Ganguli
- Massachusetts General Hospital Cancer Center , Boston, MA , USA ; Section of Interventional Radiology, Department of Imaging, Massachusetts General Hospital , Boston, MA , USA ; Department of Radiology, Harvard Medical School , Boston, MA , USA
| | - Muhammad S Beg
- Harold Simmons Cancer Center, University of Texas Southwestern Medical Center , Dallas, TX , USA ; Division of Hematology and Oncology, Department of Medicine, University of Texas Southwestern Medical Center , Dallas, TX , USA
| | - Sanjeeva P Kalva
- Harold Simmons Cancer Center, University of Texas Southwestern Medical Center , Dallas, TX , USA ; Interventional Radiology, University of Texas Southwestern Medical Center , Dallas, TX , USA
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Eichler K, Dufas T, Hammerstingl R, Gruber-Rouh T, Vogl T, Zangos S. Hepatic Arterial Infusion with Irinotecan in Patients with Liver Metastases of Colorectal Cancer: Results of an Extended Phase I Study. Chemotherapy 2013; 59:66-73. [DOI: 10.1159/000348579] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2012] [Accepted: 02/03/2013] [Indexed: 01/22/2023]
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Lu QY, Zhao AL, Deng W, Li ZW, Shen L. Hepatic histopathology and postoperative outcome after preoperative chemotherapy for Chinese patients with colorectal liver metastases. World J Gastrointest Surg 2013; 5:30-6. [PMID: 23556058 PMCID: PMC3615301 DOI: 10.4240/wjgs.v5.i3.30] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2012] [Revised: 10/03/2012] [Accepted: 12/20/2012] [Indexed: 02/06/2023] Open
Abstract
AIM: To assess the effects of preoperative treatment on the hepatic histology of non-tumoral liver and the postoperative outcome.
METHODS: One hundred and six patients underwent hepatic resection for colorectal metastases between 1999 and 2009. The surgical specimens were reviewed with established criteria for diagnosis and grading of pathological hepatic injury. The impact of preoperative therapy on liver injury and postoperative outcome was analyzed.
RESULTS: Fifty-three patients (50%) received surgery alone, whereas 42 patients (39.6%) received neoadjuvant chemotherapy and 11 (10.4%) patients received preoperative hepatic artery infusion (HAI). Chemotherapy included oxaliplatin-based regimens (31.1%) and irinotecan-based regimens (8.5%). On histopathological analysis, 16 patients (15.1%) had steatosis, 31 (29.2%) had sinusoidal dilation and 20 patients (18.9%) had steatohepatitis. Preoperative oxaliplatin was associated with sinusoidal dilation compared with surgery alone (42.4% vs 20.8%, P = 0.03); however, the perioperative complication rate was not significantly different between the oxaliplatin group and surgery group (27.3% vs 13.2%, P = 0.1). HAI was associated with more steatosis, sinusoidal dilation and steatohepatitis than the surgery group, with higher perioperative morbidity (36.4% vs 13.2%, P = 0.06) and mortality (9.1% vs 0% P = 0.02).
CONCLUSION: Preoperative oxaliplatin was associated with sinusoidal dilation compared with surgery alone. However, the preoperative oxaliplatin had no significant impact on perioperative outcomes. HAI can cause pathological changes and tends to increase perioperative morbidity and mortality.
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Affiliation(s)
- Qi-Ying Lu
- Qi-Ying Lu, Wei Deng, Lin Shen, Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University Cancer Hospital and Institute, Beijing 100142, China
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Tsimberidou AM, Leick MB, Lim J, Fu S, Wheler J, Piha-Paul SA, Hong D, Falchook GS, Naing A, Subbiah IM, Fortier A, Avritscher R, Kurzrock R. Dose-finding study of hepatic arterial infusion of oxaliplatin-based treatment in patients with advanced solid tumors metastatic to the liver. Cancer Chemother Pharmacol 2013; 71:389-97. [PMID: 23143207 DOI: 10.1007/s00280-012-2014-8] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2012] [Accepted: 10/16/2012] [Indexed: 02/03/2023]
Abstract
BACKGROUND Liver metastases in patients with cancer are associated with poor survival. We hypothesized that hepatic arterial infusion (HAI) of oxaliplatin combination therapy would have antitumor activity in these patients. PATIENTS AND METHODS Patients with advanced cancer and predominant liver metastases were treated on a phase I study of HAI oxaliplatin in combination with systemic bevacizumab, with or without HAI or systemic fluorouracil and/or leucovorin and/or cetuximab. Patients were divided into two treatment arms according to KRAS mutational status and physician choice. A "3 + 3" design was used. RESULTS Among 76 patients (median age 61 years; 34 women; median number of prior therapies 4), the most common cancer was colorectal (CRC) (n = 58). Overall, the only dose-limiting toxicity was Grade 3 diarrhea (n = 2). The most common treatment-related toxicities were hypertension (n = 40), nausea (n = 29), fatigue (n = 28), and transaminitis (n = 26). Of 76 patients, one (1 %) had a complete response (CR), 12 (16 %) had a partial response (PR), and 12 (16 %) had SD for ≥ 6 months (total CR/PR/SD ≥ 6 months 25/76 = 33 %). In CRC (n = 58), total CR/PR/SD ≥ 6 months was 31 % (n = 18). Both patients with pancreatic neuroendocrine tumors achieved a PR (24+ months) and a CR (6+ months). Time to treatment failure (TTF) on the current regimen was 3.5 versus 2.8 months on patients' prior systemic treatment (p = 0.37). CONCLUSIONS HAI oxaliplatin combination therapy with 5-fluorouracil, leucovorin, bevacizumab, and/or cetuximab was well tolerated and had antitumor activity in selected heavily pretreated patients with predominant liver disease.
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Affiliation(s)
- Apostolia M Tsimberidou
- Phase I Program, Department of Investigational Cancer Therapeutics, Unit 455, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
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Eichler K, Zangos S, Mack MG, Hammerstingl R, Gruber-Rouh T, Gallus C, Vogl TJ. First human study in treatment of unresectable liver metastases from colorectal cancer with irinotecan-loaded beads (DEBIRI). Int J Oncol 2012; 41:1213-20. [PMID: 22842404 PMCID: PMC3583653 DOI: 10.3892/ijo.2012.1572] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2012] [Accepted: 05/29/2012] [Indexed: 12/27/2022] Open
Abstract
The objective of this pilot clinical study was to assess the safety, technical feasibility, pharmacokinetic (PK) profile and tumour response of DC Bead™ with irinotecan (DEBIRI™) delivered by intra-arterial embolisation for the treatment of metastatic colorectal cancer. Eleven patients with unresectable liver metastases from CRC, tumour burden <30% of liver volume, adequate haematological, liver and renal function, performance status of <2 were included in this study. Patients received up to 4 sessions of TACE with DEBIRI at 3-week intervals. Feasibility of the procedure, safety and tumour response were assessed after each cycle. PK was measured after the first cycle. Patients were followed up to 24 weeks. Only mild to moderate adverse events were observed. DEBIRI is a technically feasibile procedure; no technical complications were observed. Average Cmax for irinotecan and SN-38 was 194 ng/ml and 16.7 ng/ml, respectively, with average t½ of 4.6 h and 12.4 h following administration of DEBIRI. Best overall response during the study showed disease control in 9 patients (2 patients with partial response and 7 with stable disease, overall response rate of 18%). Our study shows that transarterial chemoembolisation with irinotecan-loaded DC beads (DEBIRI) is safe, technically feasible and effective with a good PK profile.
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Affiliation(s)
- K Eichler
- Department of Diagnostic and Interventional Radiology, University Hospital Frankfurt, Johann Wolfgang Goethe-University, D-60590 Frankfurt, Germany.
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Parsons HA, Tsimberidou AM, Pontikos M, Fu S, Hong D, Wen S, Baracos VE, Kurzrock R. Evaluation of the clinical relevance of body composition parameters in patients with cancer metastatic to the liver treated with hepatic arterial infusion chemotherapy. Nutr Cancer 2012; 64:206-17. [PMID: 22229660 DOI: 10.1080/01635581.2012.638433] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
The association between body composition parameters and toxicity from hepatic arterial infusion (HAI) chemotherapy regimens has not been analyzed. We assessed data from patients with advanced cancer and liver metastases treated on a clinical trial of a regimen of HAI oxaliplatin combined with systemic 5-fluorouracil/leucovorin and bevacizumab. Correlations between patient characteristics, response, and toxicity and body composition data taken from CT images were analyzed. Forty-eight of 57 patients (mean age 56 yr; 60% women) had available CT scans. The most common diagnosis was colorectal cancer (22/48, 46%); 30/48 patients (63%) had body mass index (BMI) ≥25 kg/m(2). Twenty (42%) of 48 patients were sarcopenic. Grade 3-4 adverse events did not differ among patients with and without sarcopenia or according to BMI. The median survival (95% C]) was 167 (128-206) days for sarcopenic and 280 (214-346) days for nonsarcopenic patients (P = 0.271). Among patients treated at the maximum tolerated dose, the median survival was 103 days for sarcopenic and 312 days for nonsarcopenic patients (P = 0.173). Sarcopenia was present in 30% (6/20) of patients with reduction in tumor size posttreatment, and in 52% (14/27) of patients with increased tumor size (P = 0.171). In conclusion, body composition was not significantly associated with toxicities or survival in our small sample.
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Affiliation(s)
- Henrique A Parsons
- Department of Investigational Cancer Therapeutics (A Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA
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Barosh BA, Holmes C, Keerikattu LM, Manappurathu MS, Segovia JH, Hasen PC, Pai SV, Lobiondo-Wood G, Kurzrock R. Advancing the scope of nursing practice: hepatic arterial catheter removal. Clin J Oncol Nurs 2011; 15:465-8. [PMID: 21951733 DOI: 10.1188/11.cjon.465-468] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
A delay in hepatic artery infusion catheter removal may prolong patient discomfort and lead to additional complications. As a result, this article evaluated the effectiveness of shifting the responsibility of catheter removal from advanced practice or medical staff to nurses. Overall, patients were satisfied, felt comfortable, and experienced minimal pain irrespective of whether their catheter was removed by a nurse, physician, or advanced practice staff. Nurses also were satisfied and felt they had enhanced their ability to provide quality patient care.
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Fu S, Naing A, Moulder SL, Culotta KS, Madoff DC, Ng CS, Madden TL, Falchook GS, Hong DS, Kurzrock R. Phase I trial of hepatic arterial infusion of nanoparticle albumin-bound paclitaxel: toxicity, pharmacokinetics, and activity. Mol Cancer Ther 2011; 10:1300-7. [PMID: 21571911 DOI: 10.1158/1535-7163.mct-11-0259] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Because liver involvement in patients with metastatic cancer has limited options and poor outcomes, we conducted a phase I study to determine the safety, activity, and pharmacokinetic characteristics of hepatic arterial infusion of nanoparticle albumin-bound paclitaxel (HAI nab-paclitaxel). Cohorts of three patients having predominant hepatic metastases received HAI nab-paclitaxel at three dose levels (180, 220, and 260 mg/m(2), respectively) infused for more than 1 hour every 3 weeks (3 + 3 design). Some patients participated in comparative pharmacokinetic studies (i.v. vs. HAI), receiving their first course i.v., to determine peak concentrations and effect of first-pass hepatic extraction compared with subsequent courses administered by HAI. The highest dose level was expanded to determine the safety and activity of HAI nab-paclitaxel. Thirty-eight patients were treated. There were no dose-limiting toxicities at doses up to 260 mg/m(2). Common adverse events included alopecia, fatigue, myelosuppresion, nausea, and vomiting. Three patients had stable disease for 4 or more months and 2 patients (1 of 12 with breast cancer and 1 of 1 with cervical cancer) achieved a partial response lasting for 5 and 15 months, respectively. Peak concentrations were lower (∼50%) with greater hepatic extraction of drug (∼42%) following HAI than i.v. infusion based on area under the curve comparison of drug exposure. HAI nab-paclitaxel showed partial hepatic extraction. At doses 260 mg/m(2) or less given for 1 hour every 3 weeks, the treatment was well-tolerated and showed activity in advanced cancer patients with predominant liver metastases.
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Affiliation(s)
- Siqing Fu
- Department of Investigational Cancer Therapeutics, Unit 0455, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
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Camacho LH, Garcia S, Panchal AM, Lim J, Hong DS, Ng C, Madoff DC, Fu S, Gayed I, Kurzrock R. Exploratory study of hepatic arterial infusion oxaliplatin with systemic 5-fluorouracil/bevacizumab in patients with refractory solid tumor and extensive liver metastases. Clin Colorectal Cancer 2011; 9:311-4. [PMID: 21208846 DOI: 10.3816/ccc.2010.n.045] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
PURPOSE This pilot clinical trial explored the feasibility, safety, and efficacy of regional hepatic therapy combined with systemic anticancer agents in patients with refractory solid tumors and extensive unresectable liver involvement, including those with compromised hepatic function. PATIENTS AND METHODS Six patients with colorectal (N = 3), ovarian (N = 2), and hepatocellular carcinoma (N = 1) received intra-arterial hepatic oxaliplatin followed by intravenous 5-fluorouracil, leucovorin, and bevacizumab every 2 weeks until disease progression. All had extensive liver metastases; four had elevated baseline serum total bilirubin. Median total bilirubin was 2.8 mg/dL (range, 0.2-5.2 mg/dL). Median Child-Pugh score was 7 (range, 5-10). RESULTS Thirty treatments were delivered (2-7 per patient). Median age of patients was 57 years (range, 25-69 years). Three patients (1 with colorectal, 1 with hepatocellular, and 1 with ovarian cancer) attained partial responses. Two had failed previous oxaliplatin and cisplatin treatment. Some with elevated bilirubin at baseline had a significant drop in bilirubin with treatment (bilirubin 5.2 → 1 mg/dL, 4.8 → 1.1 mg/dL, and 5.2 → 1.8 mg/dL). The regimen was generally well tolerated; the most common side effects were grade 1 fatigue, anorexia, and/or hypertension. One patient died of enzyme-linked, immunoassay-confirmed, heparin-induced thrombocytopenia during the sixth cycle of therapy. CONCLUSION At doses tested, this regimen was safe and demonstrated antitumor activity in patients with advanced refractory malignancies involving the liver, including those with hepatic insufficiency. Further study is warranted.
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Affiliation(s)
- Luis H Camacho
- Department of Investigational Cancer Therapeutics, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
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Tsimberidou AM, Fu S, Ng C, Lim JA, Wen S, Hong D, Wheler J, Bedikian AY, Eng C, Wallace M, Camacho LH, Kurzrock R. A phase 1 study of hepatic arterial infusion of oxaliplatin in combination with systemic 5-fluorouracil, leucovorin, and bevacizumab in patients with advanced solid tumors metastatic to the liver. Cancer 2010; 116:4086-94. [PMID: 20564148 DOI: 10.1002/cncr.25277] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
BACKGROUND Liver metastases in patients with cancer are associated with poor survival. The authors of this report conducted a phase 1 study of hepatic arterial infusion (HAI) oxaliplatin combination therapy in patients with advanced cancer and liver metastases. METHODS Treatment consisted of escalating doses of HAI oxaliplatin 60 mg/m(2) to 175 mg/m(2) and intra-arterial heparin 3000 IU (Day 1); leucovorin 200 mg/m(2) intravenously (iv) and 5-fluorouracil 300 mg/m(2) bolus plus 600 mg/m(2) iv (Days 1 and 2); and bevacizumab 10 mg/kg iv (Day 3). A conventional "3 + 3" design was used. RESULTS Fifty-seven patients were treated, including 30 women and 27 men. The median age was 57 years, and the patients had received a median of 3 prior therapies (range, 1-7 prior therapies). The most common cancer was colorectal (n = 29). Overall, 204 cycles were administered (median per patient, 2 cycles; range, 1-17 cycles). The maximum tolerated dose (MTD) of HAI oxaliplatin was 140 mg/m(2). Dose-limiting toxicities were grade 4 thrombocytopenia (n = 1) and grade 4 hypokalemia (n = 1) at 150 mg/m(2) (n = 5). Thirty-three patients (58%) had no toxicity greater than grade 1. The most common toxicities were thrombocytopenia (n = 19), fatigue (n = 15), nausea/vomiting (n = 6), constipation (n = 6), and diarrhea (n = 4). Of 55 patients who were evaluable for response (according to Response Evaluation Criteria in Solid Tumors), 4 patients (7%) had a partial response (PR), and 32 patients (58%) had stable disease (SD), including 15 patients (48%) who had SD for >/=4 months. Of 28 patients with colorectal cancer, 3 patients (11%) had a PR, and 9 patients (32%) had SD for >/=4 months. CONCLUSIONS HAI oxaliplatin combined with systemic 5-fluorouracil, leucovorin, and bevacizumab had antitumor activity in patients with advanced cancer and liver metastases, and the current results indicated that this combination warrants further study. Cancer 2010. (c) 2010 American Cancer Society.
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Affiliation(s)
- Apostolia M Tsimberidou
- Phase I Program, Department of Investigational Cancer Therapeutics, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA
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19
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Abstract
AIM Hepatic toxicity of chemotherapy for colorectal cancer and its complications after hepatic metastasis surgery are unclear. Studies reporting hepatic lesions after chemotherapy for colorectal cancer and published before July 2009 have been identified by searching the Medline database. Data concerning these hepatic lesions and outcome after surgery are resumed in this review. RESULTS Studies concerning the link between hepatic steatosis and chemotherapy have contradictory results but steatosis is clearly associated to an increase of postoperative morbidity. Steatohepatitis, especially due to irinotecan, is associated with increased postoperative mortality. Sinusoidal obstruction syndrome, a severe form of vascular hepatic lesion, associated to oxaliplatin, seems to be linked with an increase of postoperative morbidity, but not mortality. Bevacizumab would not increase, when used in combination with oxaliplatin, the rate of postoperative complications. Some studies suggest a decrease of vascular hepatic lesions when bevacizumab is administered with chemotherapy. The literature concerning hepatic toxicity of anti-EGF-R antibody is freak. CONCLUSION The fact that irinotecan may be linked to an increased risk of hepatic failure and postoperative death, which is not the case of oxaliplatine, must be taken in consideration in the choice of the preoperative chemotherapy before resection of hepatic metastasis of colorectal cancer.
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Pencavel T, Seth R, Hayes A, Melcher A, Pandha H, Vile R, Harrington KJ. Locoregional intravascular viral therapy of cancer: precision guidance for Paris's arrow? Gene Ther 2010; 17:949-60. [PMID: 20445580 DOI: 10.1038/gt.2010.48] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Viral therapy of cancer includes strategies such as viral transduction of tumour cells with 'suicide genes', using viral infection to trigger immune-mediated tumour cell death and using oncolytic viruses for their direct anti-tumour action. However, problems still remain in terms of adequate viral delivery to tumours. A role is also emerging for single-organ isolation and perfusion. Having begun with the advent of isolated limb perfusion for extremity malignancy, experimental systems have been developed for the perfusion of other organs, particularly the liver, kidneys and lungs. These are beginning to be adopted into clinical treatment pathways. The combination of these two modalities is potentially significant. Locoregional perfusion increases the exposure of tumour cells to viral agents. In addition, the avoidance of systemic elimination through the immune and reticulo-endothelial systems should provide a mechanism for increased transduction/infection of target cells. The translation of laboratory research to clinical practice would occur within the context of perfusion programmes, which are already established in the clinic. Many of these programmes include the use of vasoactive cytokines such as tumour necrosis factor-alpha, which may have an effect on viral uptake. Evidence of activation of specific anti-tumour immunological responses by intratumoural and other existing methods of viral administration raises the intriguing possibility of a locoregional therapy, with the ability to affect distant sites of disease. In this review, we examined the state of the literature in this area and summarized current findings before indicating likely areas of continuing interest.
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Affiliation(s)
- T Pencavel
- Targeted Therapy Team, The Institute of Cancer Research, and Sarcoma/Melanoma Unit, Royal Marsden Hospital, London, UK
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21
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Phase I clinical trial of hepatic arterial infusion of cisplatin in combination with intravenous liposomal doxorubicin in patients with advanced cancer and dominant liver involvement. Cancer Chemother Pharmacol 2010; 66:1087-93. [PMID: 20204368 DOI: 10.1007/s00280-010-1266-4] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2009] [Accepted: 02/01/2010] [Indexed: 01/24/2023]
Abstract
PURPOSE We conducted a phase I study of hepatic arterial infusion (HAI) cisplatin and systemic chemotherapy in patients with advanced cancer and dominant liver involvement. METHODS Patients were treated with HAI cisplatin 100-125 mg/m(2) (and 3,000 IU heparin) intraarterially and liposomal doxorubicin (doxil) 20-35 mg/m(2) IV (day 1) every 28 days. A "3 + 3" study design was used. RESULTS Thirty patients were treated (median age, 56 years). Diagnoses were breast cancer (n = 11), colorectal cancer (n = 8), ocular melanoma (n = 4), and other (n = 7). The median number of prior therapies was 5. The maximum tolerated dose (MTD) was at the 100/35 mg/m(2) level. Dose-limiting toxicities were Grade 4 neutropenia (2 of 4 patients), and Grade 4 thrombocytopenia (n = 1) at the cisplatin 125 mg/m(2) and systemic doxil 35 mg/m(2) dose level. The most common toxicities were nausea/vomiting and fatigue. Of 24 patients evaluable for response, 4 (17%) had a partial response (PR) and 7 (29%) had stable disease (SD) for ≥4 months. Of the 11 patients with breast cancer, 3 (27%) had a PR and 5 (45%) had SD for ≥4 months. Of 4 patients with ocular melanoma, 1 had a PR and 1 SD for 4 months. One patient with hepatocellular carcinoma had SD for 4 months. Of 12 evaluable patients treated at the MTD, 2 (17%) had a PR and 5 (42%) had SD. CONCLUSION The MTD was HAI cisplatin 100 mg/m(2) and systemic doxil 35 mg/m(2). This regimen demonstrated antitumor activity, especially in breast cancer.
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Fujimoto Y, Akasu T, Yamamoto S, Fujita S, Moriya Y. Long-term results of hepatectomy after hepatic arterial infusion chemotherapy for initially unresectable hepatic colorectal metastases. J Gastrointest Surg 2009; 13:1643-50. [PMID: 19582514 DOI: 10.1007/s11605-009-0966-8] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2009] [Accepted: 06/22/2009] [Indexed: 01/31/2023]
Abstract
BACKGROUND The prognosis of unresectable hepatic colorectal metastases is poor even if chemotherapy is administered. The purpose of this study was to evaluate the long-term efficacy of hepatic arterial infusion (HAI) chemotherapy and hepatectomy following HAI for such condition. METHODS Seventy-two patients with unresectable hepatic colorectal metastases received continuous HAI of 5-fluorouracil. RESULTS The overall response rate was 38%. The median survival of all patients was 18 months. The overall 3-year survival rate was 18%. Seven patients (10%) survived more than 58 months. Of the eight patients with a complete response, seven developed liver and/or lung metastases, and of these, one patient undergoing additional hepatectomy has been disease-free and the other six receiving chemotherapy died of disease. Another complete-response case died of liver abscess. Of the 19 patients with a partial response, six could undergo hepatectomy after HAI. The overall 5-year survival rate of seven patients undergoing hepatectomy was 71%, whereas for patients without hepatectomy, the rate was 0%. CONCLUSIONS Most patients showing response after HAI for unresectable hepatic colorectal metastases had relapses. The long-term prognosis of patients undergoing hepatectomy after HAI was favorable. Therefore, when HAI makes liver metastases resectable, they should be resected.
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Affiliation(s)
- Yoshiya Fujimoto
- Colorectal Surgery Division, National Cancer Center Hospital, Tokyo, Japan
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Mocellin S, Pilati P, Lise M, Nitti D. Meta-analysis of hepatic arterial infusion for unresectable liver metastases from colorectal cancer: the end of an era? J Clin Oncol 2007; 25:5649-54. [PMID: 18065736 DOI: 10.1200/jco.2007.12.1764] [Citation(s) in RCA: 119] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
PURPOSE The treatment of unresectable liver-confined metastatic disease from colorectal cancer (CRC) is a challenging issue. Although locoregional treatments such as hepatic arterial infusion (HAI) claim the advantage of delivering higher doses of anticancer agents directly into the affected organ, the benefit in terms of overall survival (OS) is unclear. We quantitatively summarized the results of randomized controlled trials (RCT) comparing HAI with systemic chemotherapy (SCT). METHODS To date, 10 RCTs have been published, for a total of 1,277 patients enrolled. For tumor response rates, relative risks (RR) and their 95% CIs were obtained from raw data; for OS, hazard ratios (HRs) and their 95% CIs were extrapolated from the Kaplan-Meier survival curves. RESULTS HAI regimens were based on floxuridine (FUDR) in nine of 10 RCTs, whereas in one RCT, fluorouracil (FU) + leucovorin was used. SCT consisted of FUDR, FU, FU + leucovorin, or a miscellany of FU and best supportive care in three, one, four, and two studies, respectively. Pooling the data, tumor response rate was 42.9% and 18.4% for HAI and SCT, respectively (RR = 2.26; 95% CI, 1.80 to 2.84; P < .0001). Mean weighted median OS times were 15.9 and 12.4 months for HAI and SCT, respectively; the meta-risk of death was not statistically different between the two study groups (HR = 0.90; 95% CI, 0.76 to 1.07; P = .24). CONCLUSION Currently available evidence does not support the clinical or investigational use of fluoropyrimidine-based HAI alone for the treatment of patients with unresectable CRC liver metastases, at least as a first-line therapy.
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Affiliation(s)
- Simone Mocellin
- Clinica Chirurgica Generale 2, Department of Oncological and Surgical Sciences, University of Padova, via Giustiniani 2, 35128 Padova, Italy.
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24
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Mantke R, Niepmann D, Gastinger I, Lippert H, Koch K, Quehl A. [Hepatic resections. Analysis of data from the Tumor Documentation Center in the state of Brandenburg, Germany, focusing on liver metastases of colorectal carcinoma]. Chirurg 2007; 77:1135-43. [PMID: 17091286 DOI: 10.1007/s00104-006-1247-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
BACKGROUND Data from the Brandenburg Tumor Documentation Center (TDCB) in Germany were analyzed for an overview of the current treatment standards of liver surgery in that state. MATERIAL AND METHODS The analysis was based on prospective data from a total of 37,165 patients diagnosed with malignant tumors between 1 January 1999 and 31 December 2004. Of these patients, 3,986 were diagnosed with liver metastases and 554 had primary tumors of the liver or bile duct. Liver metastases of colorectal carcinoma were reported in 1,299. RESULTS Analysis confirmed that resection of colorectal metastases (51%) and primary liver or bile duct tumors (23.1%) is by far the most frequent indication for liver surgery. Liver metastasis was developed by 29.2% (n=1299) of patients with colorectal carcinoma. Of the patient total, 71.5% showed evidence of liver metastasis already present when colorectal carcinoma was diagnosed. Of 248 patients who had received liver surgery after diagnosis of liver metastases of a colorectal carcinoma, 114 (46%) underwent hepatic segment resection, which was thus performed in only 8.8% (n=114) of patients with liver metastases after colorectal carcinoma (n=1299). CONCLUSIONS Since only 8.8% of those with liver metastases underwent curative hepatic segment resection, we can conclude that if patients and doctors were provided with adequate information on the curative potential of this surgical method along with regular consultations with surgeons experienced in liver surgery, the result on resection rates would be positive. Data from tumor documentation centers enable selective analysis of the oncological situation of specific diseases.
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Affiliation(s)
- R Mantke
- Klinik für Allgemein- und Viszeralchirurgie, Städtisches Klinikum, Hochstrasse 29, 14770 Brandenburg, Deutschland.
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Marelli L, Shusang V, Senzolo M, Cholongitas E, Goode A, Yu D, Patch DW, Burroughs AK. Repeated courses of transarterial embolization with polyvinyl alcohol particles: 'long life elixir' in a cirrhotic patient with unresectable hepatocellular carcinoma. Eur J Gastroenterol Hepatol 2007; 19:329-32. [PMID: 17353698 DOI: 10.1097/meg.0b013e3280298391] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Chemoembolization improves survival in selected cirrhotic patients with hepatocellular carcinoma, but prolonged survival is unusual. In this study, a 70-year-old cirrhotic patient, who had a histologically proven hepatocellular carcinoma of 5 cm diameter, embolization with polyvinyl alcohol particles alone, without chemotherapeutic agent, has resulted in continued survival, of 5 years to date, with virtual elimination of residual hypervascularity following 10 sessions of embolization, and with continued patency of the injected branch of the hepatic artery. Provided liver function is maintained, embolization alone appears a feasible long term and effective therapy for unresectable hepatocellular carcinoma.
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Affiliation(s)
- Laura Marelli
- Liver Transplantation and Hepatobiliary Medicine Unit, Royal Free Hospital, London, UK
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Schillaci O, Filippi L, Danieli R, Simonetti G. Single-Photon Emission Computed Tomography/Computed Tomography in Abdominal Diseases. Semin Nucl Med 2007; 37:48-61. [PMID: 17161039 DOI: 10.1053/j.semnuclmed.2006.07.001] [Citation(s) in RCA: 46] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Single-photon emission computed tomography (SPECT) studies of the abdominal region are established in conventional nuclear medicine because of their easy and large availability, even in the most peripheral hospitals. It is well known that SPECT imaging demonstrates function, rather than anatomy. It is useful in the diagnosis of various disorders because of its ability to detect changes caused by disease before identifiable anatomic correlates and clinical manifestations exist. However, SPECT data frequently need anatomic landmarks to precisely depict the site of a focus of abnormal tracer uptake and the structures containing normal activity; the fusion with morphological studies can furnish an anatomical map to scintigraphic findings. In the past, software-based fusion of independently performed SPECT and CT or magnetic resonance images have been demonstrated to be time consuming and not useful for routine clinical employment. The recent development of dual-modality integrated imaging systems, which provide SPECT and CT images in the same scanning session, with the acquired images co-registered by means of the hardware, has created a new scenario. The first data have been mainly reported in oncology patients and indicate that SPECT/CT is very useful because it is able to provide further information of clinical value in several cases. In SPECT studies of abdominal diseases, hybrid SPECT/CT can play a role in the differential diagnosis of hepatic hemangiomas located near vascular structures, in precisely detecting and localizing active splenic tissue caused by splenosis in splenectomy patients, in providing important information for therapy optimization in patients submitted to hepatic arterial perfusion scintigraphy, in accurately identifying the involved bowel segments in patients with inflammatory bowel diseases, and in correctly localizing the bleeding sites in patients with gastrointestinal bleeding.
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Affiliation(s)
- Orazio Schillaci
- Department of Biopathology and Diagnostic Imaging, University "Tor Vergata," Rome, Italy.
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Bartlett DL, Berlin J, Lauwers GY, Messersmith WA, Petrelli NJ, Venook AP. Chemotherapy and regional therapy of hepatic colorectal metastases: expert consensus statement. Ann Surg Oncol 2006; 13:1284-92. [PMID: 16955384 DOI: 10.1245/s10434-006-9018-8] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2006] [Accepted: 06/02/2006] [Indexed: 01/08/2023]
Affiliation(s)
- David L Bartlett
- Division of Surgical Oncology, University of Pittsburgh, Pennsylvania, USA
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28
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Vogl TJ, Zangos S, Eichler K, Yakoub D, Nabil M. Colorectal liver metastases: regional chemotherapy via transarterial chemoembolization (TACE) and hepatic chemoperfusion: an update. Eur Radiol 2006; 17:1025-34. [PMID: 16944163 DOI: 10.1007/s00330-006-0372-5] [Citation(s) in RCA: 98] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2006] [Revised: 05/26/2006] [Accepted: 06/19/2006] [Indexed: 01/15/2023]
Abstract
Liver metastasis is one of the main problems encountered in colorectal cancer management as the liver is the most common metastatic site. Several treatment options are available, among which transarterial chemotherapy has proved effective in achieving some local tumour control, improving the quality of life through symptomatic control as well as survival time. The present paper is intended to provide an overview of the techniques, indications and results of regional chemotherapy, which comprises transarterial chemoembolization (TACE) and chemoperfusion. This treatment approach has symptomatic, palliative, adjuvant and potentially curative objectives. We reviewed the studies involving TACE and chemoperfusion of colorectal liver metastases during the last few years to update the previous reviews published on this subject. The results achieved were so variable, due to the variations in patient selection criteria and regimens used between the different studies. The median survival ranged from 9 to 62 months and the morphological response ranged from 14 to 76%. Technical aspects, results, and complications of this modality will be demonstrated with a detailed analysis and comments.
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Affiliation(s)
- Thomas J Vogl
- Institute for Diagnostic and Interventional Radiology, Johann Wolfgang Goethe-University Clinic, Theodor-Stern-Kai 7, 60590, Frankfurt am Main, Germany.
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Alazmi WM, McHenry L, Watkins JL, Fogel EL, Schmidt S, Sherman S, Lehman GL. Chemotherapy-induced sclerosing cholangitis: long-term response to endoscopic therapy. J Clin Gastroenterol 2006; 40:353-7. [PMID: 16633109 DOI: 10.1097/01.mcg.0000210098.28876.66] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Abstract
BACKGROUND Hepatic arterial infusion of fluoropyrimidines has been widely used for the treatment of hepatic metastasis from colorectal cancer. One major complication of such treatment is biliary sclerosis resembling primary sclerosing cholangitis, which has an incidence ranging from 8% to 26%. AIM We evaluated the efficacy and long-term outcome of endoscopic therapy in the management of chemotherapy-induced sclerosing cholangitis (CISC). METHODS With the use of an endoscopic retrograde cholangiopancreatography (ERCP) database, all patients with a diagnosis of CISC who had endoscopic therapy between March 1995 and March 2005 were identified. The indications, findings, therapies, and complications for all patients undergoing ERCP were recorded in this database. Additional information was obtained by review of medical records. RESULTS Eleven patients (six men and five women) were identified. The mean age at presentation was 59.5 years (range, 36-76 years). Cholangiogram findings revealed stricture confined to the common hepatic duct in two patients, involving the hilum in seven patients, involving the right and/or left main hepatic ducts in nine patients, and extending to the intrahepatic radicals in two patients. All patients had successful endoscopic therapy to alleviate the presenting symptom. The grade and extent of biliary strictures did not change in five patients, improved in one patient, recurred in two patients, and progressed in two patients over the follow-up period of 28.2 months (range, 4-60 months). CONCLUSION Although long-term follow-up of patients with CISC is limited by the dismal prognosis of the underlying malignancy, CISC has a recalcitrant pattern that rarely improves with endoscopic therapy. However, endoscopic therapy seems to be an effective method of palliation.
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Affiliation(s)
- Waleed M Alazmi
- Indiana University Medical Center, 550 N. University Blvd, Indianapolis, 46202, USA
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Abstract
The liver is the most common site of metastases in patients with colorectal cancer (CRC), and hepatic metastases are responsible for fatalities in at least two thirds of patients with colorectal malignancy. However, the only available treatment associated with long-term survival in patients with CRC metastases is liver resection. While recent studies have shown that liver resection achieves a 5-year overall survival from 37% to 58%, only 10% to 20% of patients with colorectal liver metastases are eligible for resection. Pharmacologic developments and conceptual advances in chemotherapy, regional treatment, and aggressive surgical strategies have ultimately changed the current treatment of patients with primary unresectable liver metastases caused by CRC. Patients who were treated by only palliative chemotherapy a few years ago presently have a variety of strategies available to render their disease surgically resectable with the potential for long-term survival. These advances are the result of a strong collaboration between medical oncologists and surgeons. The development of new chemotherapy protocols that offer the potential for curative surgery with optimum timing within the natural history of this metastatic disease is a shared therapeutic challenge.
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Affiliation(s)
- Eric Vibert
- Centre Hépato-biliaire, Hopîtal Paul Brousse Hospital, Assistance Publique / Hôpitaux de Paris, Université de Paris -Sud, Villejuif, France
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Sheth KR, Clary BM, Ychou M, Delpero JR, Rougier P. Management of hepatic metastases from colorectal cancer. Clin Colon Rectal Surg 2005; 18:215-23. [PMID: 20011304 PMCID: PMC2780092 DOI: 10.1055/s-2005-916282] [Citation(s) in RCA: 63] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The majority of hepatic metastases in the United States occur in patients with a primary colorectal malignancy. Advances in technology combined with increasing surgeon experience have broadened the treatment options available for hepatic metastases from colorectal cancer. Surgical resection is the most effective therapy for metastatic colorectal cancer isolated to the liver. The aim of this article is to discuss the role of locally aggressive treatment options including resection, ablation, and regional chemotherapy in the management of patients with metastases from colorectal cancer.
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Affiliation(s)
- Ketan R. Sheth
- Division of Hepatobiliary Surgery, Duke University Medical Center, Durham, North Carolina
| | - Bryan M. Clary
- Division of Hepatobiliary Surgery, Duke University Medical Center, Durham, North Carolina
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Glasgow SC, Chapman WC. Emerging Technology in the Treatment of Colorectal Metastases to the Liver. SEMINARS IN COLON AND RECTAL SURGERY 2005. [DOI: 10.1053/j.scrs.2005.08.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
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Li CJ, Wang L, Tu XH, Song JX. Mechanism of thermochemotherapy with 5-fluorocytosine on human colon cancer cell line SW480 transfected cytosine deaminase gene. Shijie Huaren Xiaohua Zazhi 2004; 12:2307-2311. [DOI: 10.11569/wcjd.v12.i10.2307] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the mechanism of thermochemotherapy with 5-fluorocytosine (5-FC) on human colon cancer cell line SW480 transfected carcinoembryonic antigen (CEA) tissue-specific cytosine deaminase (CD) in vitro.
METHODS: Recombinant retroviral vector G1CEACDNa, in which the CD gene was controlled under the CEA promoter, was introduced through liposome technique to human colorectal carcinoma cell line SW480, and then the cells were selectively cultured in G418. The proliferated colonies were treated with the combined therapy of 5-FC and hyperthermia at a temperature of 43 ℃ for 30 min, 3 times. RT-PCR was performed to detect the expression of CD gene in target cells after being heated. The cell survival rate was detected by MTT method. The ultrastructures of cells were observed by electron microscopy and apoptosis was verified by flow cytometry.
RESULTS: The expression of CD genes in target cells was detected after being heated. After transfection, SW480-CEACD cells were more sensitive than their parental cells (P <0.01, t = 5.620, n = 9) to 5-FC, the killing effect of hyperthermia on SW480 cells was observed (P <0.05, t = 2.999, n = 9). Furthermore, after being treated with thermoche-motherapy of 5-FC at a temperature of 43 ℃ for 30 min, the killing effect on SW480-CEACD cells was more significant than that on SW480 cells (P <0.01, t = 4.356, n = 9). Treatment with the combination of 5-FC and hyperthermia displayed a higher anti-tumor effect than that with 5-FC alone on SW480-CEACD cells in vitro (P <0.05, t = 2.376, n = 9). Apoptotic bodies in the field of electron microscope were observed. G1 blockage was confirmed and the increased rate of apoptosis cells was verified after hyperthermia with 5-FC by flow cytometry.
CONCLUSION: The combination of 5-FC and hyperthermia will result in G1 blockage of human colorectal carcinoma cell lines SW480 transfected with the CEA tissue-specific CD genes, which will improve the outcome of the anti-tumor effect on that cell line.
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