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Management of acute chemotherapy-related diarrhea

Authors
Smitha S Krishnamurthi, MD
Carole Macaron, MD
Section Editor
Reed E Drews, MD
Deputy Editor
Diane MF Savarese, MD

INTRODUCTION

Most chemotherapeutic agents target rapidly dividing cells, and effects on these cells within the gastrointestinal tract can lead to a variety of symptoms. Diarrhea caused by chemotherapy, referred to here as chemotherapy-related diarrhea (CRD), is a common problem in cancer patients and is most often described with fluoropyrimidines (particularly fluorouracil [FU] and capecitabine) and irinotecan. Diarrhea is often the dose-limiting and major toxicity of regimens containing a fluoropyrimidine with irinotecan. The frequency of severe (grade 3 or 4 (table 1)) diarrhea with these agents ranges from 5 to 44 percent, and rates vary according to the dose, the specific agents administered, and the schedule of administration. (See "Enterotoxicity of chemotherapeutic agents", section on 'Fluorouracil' and "Enterotoxicity of chemotherapeutic agents", section on 'Irinotecan'.)

In addition to conventional cytotoxic drugs, such as fluoropyrimidines and irinotecan, several molecularly targeted agents are also associated with CRD:

For many tyrosine kinase inhibitors (TKIs), such as afatinib, ceritinib, erlotinib, lapatinib, sorafenib, and sunitinib, diarrhea is second only to rash as the most common toxicity. Diarrhea develops in approximately one-half of treated patients, although the incidence of severe (grade 3 or 4) diarrhea is lower than with conventional cytotoxic agents. Diarrhea is especially common with ceritinib and afatinib, occurring in 75 to 86 percent of treated patients, but severe in only 6 to 16 percent. (See "Enterotoxicity of chemotherapeutic agents", section on 'Small molecule EGFR inhibitors' and "Enterotoxicity of chemotherapeutic agents", section on 'Small molecule inhibitors of VEGFR' and "Enterotoxicity of chemotherapeutic agents", section on 'Lapatinib and pertuzumab' and "Enterotoxicity of chemotherapeutic agents", section on 'ALK inhibitors'.)

Monoclonal antibodies directed against the epidermal growth factor receptor (EGFR) rarely cause severe diarrhea when used as monotherapy but can increase the incidence of severe diarrhea when combined with cytotoxic chemotherapy. (See "Enterotoxicity of chemotherapeutic agents", section on 'Anti-EGFR monoclonal antibodies'.)

The antiangiogenic agent aflibercept, which is a recombinant fusion protein of the vascular endothelial growth factor (VEGF) binding portions of the VEGF receptors 1 and 2 fused to the Fc portion of human immunoglobulin G1 (IgG1), increased severe diarrhea by 10 percent when added to FOLFIRI (irinotecan plus leucovorin and short-term infusional FU) chemotherapy [1]. When added to FOLFOX (oxaliplatin plus leucovorin and short-term infusional FU) chemotherapy, aflibercept increased the incidence of severe diarrhea by 8 percent [2].

                                      

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Literature review current through: Jul 2017. | This topic last updated: Feb 13, 2017.
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