Characterisation and clinical management of CPT-11 (irinotecan)-induced adverse events: the European perspective.
CPT-11 (Campto, irinotecan) is a promising new agent in the treatment of advanced colorectal cancer. Its safety has been assessed in light of the results from recent European phase II studies. In a pivotal French study in which CPT-11 350 mg/m2 was administered once every 3 weeks, neutropenia and delayed diarrhoea were the major adverse events: transient neutropenia occurred in 80% of patients, and severe neutropenia and febrile neutropenia in 47 and 15%, respectively. Delayed diarrhoea occurred in 87% of patients, with 39% having severe (grade 3 or 4) diarrhoea and 16% requiring hospitalisation. None of these adverse events was cumulative. Results of a pilot study to elucidate the mechanism of CPT-11-induced delayed diarrhoea suggest that this toxicity has a secretory mechanism with an exudative component. Early appropriate management of delayed diarrhoea may improve the safety profile of CPT-11. Indeed, the safety profile of CPT-11 was clearly improved in a later (currently ongoing) pan-European study: incidences of severe (grade 3 or 4) delayed diarrhoea and febrile neutropenia (+/-infection) were reduced from 39% to 23% (grade 4: 8% to 2.5%) and from 12% to 6%, respectively. Such an improvement could be attributed to a better understanding of the mechanisms of diarrhoea, improved patient selection criteria, better education of patients and physicians about management of delayed diarrhoea and the use of broad spectrum antibiotics when diarrhoea persisted despite loperamide therapy.
Bleiberg
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Gastroenterology and Chemotherapy Department, Institut Jules Bordet, Brussels, Belgium.
Cvitkovic
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D000293:Adolescent; D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects* / Q000627:therapeutic use; D002166:Camptothecin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D017322:Clinical Trials, Phase II as Topic; D015179:Colorectal Neoplasms / Q000188:drug therapy; D003967:Diarrhea / Q000139:chemically induced* / Q000188:drug therapy; D006801:Humans; D000077146:Irinotecan; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced
D000972:Antineoplastic Agents, Phytogenic; D000077146:Irinotecan; D002166:Camptothecin