Anti-Colorectal Cancer Chemotherapy-Induced Diarrhoea: Current Treatments and Side-Effects (original) (raw)
Related papers
Chemotherapy-induced diarrhea: pathophysiology, frequency and guideline-based management
Therapeutic advances in medical oncology, 2010
Diarrhea is one of the main drawbacks for cancer patients. Possible etiologies could be radiotherapy, chemotherapeutic agents, decreased physical performance, graft versus host disease and infections. Chemotherapy-induced diarrhea (CID) is a common problem, especially in patients with advanced cancer. The incidence of CID has been reported to be as high as 50-80% of treated patients (≥30% CTC grade 3-5), especially with 5-fluorouracil bolus or some combination therapies of irinotecan and fluoropyrimidines (IFL, XELIRI). Regardless of the molecular targeted approach of tyrosine kinase inhibitors and antibodies, diarrhea is a common side effect in up to 60% of patients with up to 10% having severe diarrhea. Furthermore, the underlying pathophysiology is still under investigation. Despite the number of clinical trials evaluating therapeutic or prophylactic measures in CID, there are just three drugs recommended in current guidelines: loperamide, deodorized tincture of opium and octreot...
Cancer Chemotherapy and Pharmacology, 2014
Methods One hundred and fourteen patients receiving FOlFOX (95 patients, 530 cycles), FOlFOX + monoclonal antibodies (10 patients, 49 cycles) or FOlFIrI (9 patients, 50 cycles) were enrolled. CID was identified from diaries at baseline and daily during up to 8 chemotherapy cycles using supplemental questions on the Oral Mucositis Daily Questionnaire, a valid tool for collecting patient-reported outcomes of regimen-related mucosal injury. Patients scored CID severity from 0 "none" to 10 "worst possible," and quantity from "little" to "severe" on a 5-point scale. Quality of life was measured using the FaCt-g, and fatigue using the FaCIt fatigue scale. Results CID occurred in 89 % of patients on FOlFIrI, 50 % on FOlFOX + monoclonal antibodies and 56 % on FOlFOX alone. the risk of a first episode was highest during Cycle 1 (35 %) and dropped to <10 % during Cycles 3-5. Patients with CID reported poorer quality of life scores than those without CID (77.1 vs 80.7). Conclusions Diarrhea occurs more commonly than typically appreciated during chemotherapy for CrC. risk is highest during first exposure, suggesting variable susceptibility. Identification of this high-risk subgroup for prophylaxis could improve the quality of life.
Management of Cancer Treatment–Related Diarrhea
Journal of Pain and Symptom Management, 2000
The cancer treatment-related diarrhea caused by acute graft-versus-host disease (GVHD) and chemotherapeutic agents, particularly fluoropyrimidines and irinotecan, significantly affects patient morbidity and mortality. The mechanisms causing cancer treatment-related diarrhea are not fully understood, but histopathologic evidence points to a multifactorial process that causes an absorptive and secretory imbalance in the small bowel. Cancer treatment-related diarrhea could be life-threatening, yet assessment and treatment are not currently standardized. Several clinicians participated in a closed roundtable meeting to review the mechanisms of chemotherapy-induced diarrhea (CID) and GVHD-induced diarrhea, management issues in cancer treatment-induced diarrhea, and pharmacologic approaches to treatment. The meeting produced a proposal for new treatment guidelines and an algorithm, which include the use of octreotide for the management of CID-and GVHD-induced diarrhea. The development of diarrhea assessment guidelines that expand on the current National Cancer Institute criteria and allow for better patient management was also proposed.
New Lessons From "Old" Chemotherapy in Colorectal Cancer
Journal of Clinical Oncology, 2008
The standard of care in the treatment of metastatic colorectal cancer has seen a rapid evolution over the past 10 years. In clinical practice, combination regimens consisting of a fluoropyrimidine plus either irinotecan or oxaliplatin now commonly form the backbone for the addition of a biologic agent. In the first-line setting, this biologic agent is routinely bevacizumab; in subsequent lines of therapy, antibodies against the epidermal growth factor receptor (EGFR) are introduced, again mainly in combination with conventional cytotoxic chemotherapy. Presently ongoing clinical trials focus almost exclusively on defining the best strategy to integrate these biologic agents into palliative (or adjuvant) treatment algorithms, or on biomarkerdriven patient selection (eg, by using KRAS mutations to select a patient population with a greater likelihood of responding to EGFRtargeted approaches). 2 Based on this current generation of ongoing trials, one might think that all pertinent questions related to conventional chemotherapy in colorectal cancer have been solved, and that it is time to move on beyond the nonselective, one-size-fits-all treatment decisions to a more sophisticated approach toward colorectal cancer. Indeed, the past 10 years have seen a plethora of definitive results from clinical trials which have shaped our current standard treatment approaches. We have learned that infusional fluorouracil (FU) is a much more appropriate backbone for the addition of irinotecan and/or oxaliplatin than bolus FU. We have seen that capecitabine can serve as substitute for FU in combination regimens with oxaliplatin, but that combinations with irinotecan can be problematic. 4,5 Eventually, we have recognized that with all treatment options available, one particular treatment sequence is not superior to another, but that within clinical trials, the overall survival of patients with metastatic colorectal cancer is tightly correlated with the percentage of patients who are treated with all three active agents, fluoropyrimidine, irinotecan, and oxaliplatin. In view of all this knowledge on conventional chemotherapy, what could a trial of second-line irinotecan alone versus irinotecan plus oxaliplatin (IROX) after failure of FU/leucovorin (LV) tell us about palliative treatment algorithms in colorectal cancer in 2008? Currently, at least in the United States, few patients are treated with FU/LV alone as first-line therapy, and definitive first-line results with IROX are available from the pivotal phase III N9741 trial in which it was found to be inferior to FOLFOX4, but superior to IFL (bolus FU/LV plus irinotecan). In this issue of Journal of Clinical Oncology, Haller et al 7 present the results of a phase III trial in advanced colorectal cancer which 628 patients who had shown tumor progression FU/LV were randomly assigned to either irinotecan or IROX. It is important to note that the time of patient accrual (January 2001 to April 2004) largely predates the era of biologics in colorectal cancer, and even oxaliplatin was not routinely available everywhere during that time. Haller et al report that IROX was found to be the superior second-line therapy with regard to overall survival, time to tumor progression, response rate, and improvement in tumor-related symptoms. In fact, the median overall survival for both arms was in the upper range of expectation, with 11.1 months and 13.4 months for irinotecan and IROX, respectively. The incremental gain in median progression-free survival (2.5 months) achieved with IROX over irinotecan alone translated almost exactly into the same incremental gain in overall survival. This finding is notable given the relatively high percentage of patients (46%) in the irinotecan arm who subsequently received an oxaliplatin-based therapy, although almost half of these patients received oxaliplatin as single agent in third-line therapy which is know to have very limited activity. The results of the Haller et al trial are very similar to the findings of N9841, a phase III trial which randomly assigned 491 patients in second-line after FU/LV failure to either irinotecan or FOLFOX4 with optional cross-over in third-line therapy. 9 The overall survival for both arms was remarkably long but not statistically different (14.7 months for irinotecan, 13.5 months for FOLFOX4), conceivably due to the high rate of cross-over (51% for FOLFOX4, 38% for irinotecan). These results again highlight the sequence-independent overall survival effect of utilizing all three active cytotoxic agents in the course of therapy.
Journal of Clinical Oncology, 2014
Purpose Chemotherapy-induced diarrhea (CID) is a relatively common adverse event in the treatment of patients with colorectal cancer. The LAR for Chemotherapy-Induced Diarrhea (LARCID) trial evaluated the efficacy and safety of long-acting release octreotide (octreotide LAR) for the prevention of CID in this population. Patients and Methods Patients with colorectal cancer starting adjuvant or first-line treatment with a chemotherapy combination containing fluorouracil, capecitabine, and/or irinotecan were randomly assigned to receive octreotide LAR 30 mg intramuscularly every 4 weeks (experimental arm) or the physician's treatment of choice in case of diarrhea (control arm). Results A total of 139 patients were randomly assigned, most of whom received fluorouracil- and oxaliplatin-containing chemotherapy regimens. The rate of diarrhea was 76.1% in the experimental group (n = 68) and 78.9% in the control group (n = 71). Treatment with octreotide LAR did not prevent or reduce the ...
Predictive factors for chemotherapy-related toxic effects in patients with colorectal cancer
Nature Clinical Practice Oncology, 2008
Colorectal cancer is the second leading cause of death from cancer worldwide, and in 2007 the disease was estimated to cause the death of 52,180 Americans. 1 Approximately 60% of patients with colorectal cancer will require systemic therapy for metastatic disease, either at diagnosis or in response to disease recurrence. For more than three decades, the therapeutic options for patients with advanced colorectal cancer have been based on fluorouracil (5-FU). This agent, combined with folinic acid, remains the standard therapy for this disease, both in the metastatic and in the adjuvant setting; nonetheless, the treatment results remain unsatisfactory overall. 2-4 An updated recommendation for the treatment of colorectal cancer was made at the 1997 annual ASCO meeting. In an adjuvant study, treatment with one of the following three regimens was recommended as appropriate for patients with stage III colon cancer: 5-FU and levamisole for 1 year; 5-FU and low-dose leucovorin for 6 months; or 5-FU and high-dose leucovorin for 6 months. 5 On the basis of the results of the MOSAIC trial, 6 most oncologists posit that oxaliplatin combined with 5-FU and leucovorin should be considered standard therapy in stage III colorectal cancer, and this recommendation is further supported by consensus at the recent ASCO meeting. The use of adjuvant chemotherapy in stage II disease, however, is still controversial. Analysis of the MOSAIC trial reveals that addition of oxaliplatin to infusional 5-FU plus leucovorin (a regimen known as FOLFOX4) results in improved disease-free survival in stage II patients. When judged on the basis of hazard ratio values, the results of the MOSAIC trial are comparable to those observed in stage III patients treated with only 5-FU plus leucovorin. 6 Despite these advances, the majority of patients with stage II colorectal cancer are cured by surgery alone. Nonetheless, a better means of identifying whether stage II patients are at low or high risk of recurrence are needed. Previous studies in patients with stage III disease identified Colorectal cancer represents a major health problem in the Western world. Many drugs have been used for the treatment of this disease, but there is little information about how predictive factors can be used to aid treatment response and anticipate toxic effects related to anticancer treatment in colorectal cancer. In this Review we analyze the main data about this field of investigation, and highlight the most important predictive factors that relate to the toxic effects experienced by colorectal cancer patients treated with anticancer chemotherapy, both in the adjuvant and in the advanced settings. The predictive factors are grouped on the basis of the different anticancer drugs. We discuss the rationale for tailoring anticancer treatment in patients with colorectal cancer according to individual molecular and clinical features, with the aim of improving response rates and reducing the incidence of toxic events.
Supportive Care in Cancer, 2006
Background Diarrhoea and constipation are common toxicities of chemotherapy, and both are poorly understood. They are manifestations of alimentary mucositis, a condition which affects the entire gastrointestinal tract. Discussion The absolute percentage of patients that have diarrhoea or constipation as a result of their treatment has yet to be fully defined, although general estimates place 10% of patients with advanced cancer as being afflicted. Although there has been some major progress in recent years with understanding the mechanisms of oral and small intestinal mucositis, diarrhoea and constipation have received very little attention. Although diarrhoea is a well-recognised side-effect of both chemotherapy and radiotherapy, very little research has been conducted on the mechanisms behind diarrhoea or its treatment. Much of the information in the published literature is based on clinical observations with very little basic science existing. Constipation is not as well recognised and very little is known about its mechanisms. Objectives This review will examine in detail the potentially complex pathogenesis of post-chemotherapy diarrhoea in both animal models and the clinical setting. Furthermore, it will explore what is known about chemotherapy-induced constipation. It will then outline an evidence-based pathway for the investigation and treatment of post-chemotherapy diarrhoea and constipation.