title: A risk-benefit assessment of irinotecan in solid tumours.
abstract: Irinotecan is a water-soluble camptothecin analogue. Its cytotoxicity effects are exerted through interaction with the topoisomerase I-DNA complex, eventually leading to cell death. In preclinical studies, irinotecan has demonstrated a broad spectrum of activity in vitro and in vivo, and synergistic effects have been observed when it is administered in combination with other antineoplastic agents. Phase I studies of irinotecan conducted in Europe, Japan and the US have provided useful information on optimal dosage and scheduling, as well as thorough evaluation of the toxicity profile of the drug. Phase II and III trials utilising either irinotecan alone or in innovative combinations with other drugs are currently in progress. Available data indicate that irinotecan alone or in combination with other cytotoxic agents has therapeutic potential in several types of malignancy, including colorectal, lung, ovarian, cervical and gastric cancers and non-Hodgkin's lymphoma. It is the first drug since fluorouracil to possess consistent antitumour activity against metastatic colorectal cancer. The principal toxicities associated with irinotecan are diarrhoea and leucopenia. Effective strategies have been developed to circumvent both the early- and delayed-onset diarrhoea induced by irinotecan, thus allowing safer delivery of this promising agent in the clinical setting.
authors.affiliation: Institute for Drug Development, Cancer Therapy and Research Center, San Antonio, Texas, USA.
authors.forename: L L
authors.initials: LL
authors.lastname: Siu
authors.forename: E K
authors.initials: EK
authors.lastname: Rowinsky
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D002945:Cisplatin / Q000008:administration & dosage / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy; D003967:Diarrhea / Q000139:chemically induced; D004359:Drug Therapy, Combination; D005047:Etoposide / Q000008:administration & dosage / Q000627:therapeutic use; D005472:Fluorouracil / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D000077146:Irinotecan; D008175:Lung Neoplasms / Q000188:drug therapy; D009369:Neoplasms / Q000188:drug therapy*; D018570:Risk Assessment
chemical_list: D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D005047:Etoposide; D000077146:Irinotecan; D002945:Cisplatin; D005472:Fluorouracil; D002166:Camptothecin