Chemotherapy-induced diarrhea: pathophysiology, frequency and guideline-based management

Abstract

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 octreotide. Newer strategies and more effective agents are being developed to reduce the morbidity and mortality associated with CID. Recent research focusing on the prophylactic use of antibiotics, budesonide, probiotics or activated charcoal still have to define the role of these drugs in the routine clinical setting. Whereas therapeutic management and clinical work-up of patients presenting with diarrhea after chemotherapy are rather well defined, prediction and prevention of CID is an evolving field. Current research focuses on establishing predictive factors for CID like uridine diphosphate glucuronosyltransferase-1A1 polymorphisms for irinotecan or dihydropyrimidine-dehydrogenase insufficiency for fluoropyrimidines.

Keywords: chemotherapy-induced diarrhea; frequency; irinotecan; loperamide; octreotide; pathophysiology; prevention management.

Figure 1.

Metabolism of irinotecan. UGT, UDP glucuronosyltransferase; SN-38, 7-ethyl-10-hydroxycamptothecin;, CYP, cytochrome P450;, CES carboxylesterases; APC, 7-ethyl-10-[4-N-(5-aminopentanoic acid)-1-piperidino]carbonyloxycamptothecin; NPC, 7-ethyl-10-(4-amino-1-piperidino)carbonyloxy-camptothecin; M, oxidized metabolite; ABCB/C, ATP-binding cassette, sub-family B/C.

Figure 2.

Consensus guideline for the treatment of chemotherapy induced diarrhea [Benson et al. 2004]. Reprinted with permission © 2008 American Society of Clinical Oncology. All rights reserved.