title: Irinotecan: toward clinical end points in drug development.
abstract: The objective response rate is the initial method to assess the activity of a novel anticancer agent. Response rates may not characterize a new agent's clinical benefit, however, especially if moderate to severe toxicity may be associated with treatment. Clinical end points, such as improvement in survival or relief of disease-related symptoms, provide clinicians with a more rational basis for selecting therapies. Irinotecan (CPT-11 [Camptosar]) was introduced into clinical practice based primarily on its consistent phase II activity (response rates of 13.3% to 21.7% in patients with advanced colorectal cancer refractory to 5-fluorouracil [5-FU]). Two recently presented, randomized, phase III trials have examined irinotecan's impact on clinical end points of survival, quality of life, tolerability, and control of disease-related symptoms in 5-FU-refractory colorectal cancer patients. The first trial prospectively compared irinotecan and best supportive care (BSC) to BSC alone in patients with 5-FU-resistant metastatic colorectal cancer. Irinotecan-treated patients had significantly prolonged survival, improved quality of life, and better control of disease-related symptoms. The second trial compared irinotecan to infusional 5-FU schedules in colorectal cancer patients whose tumors had progressed within 3 months of prior 5-FU. Patients treated with irinotecan lived significantly longer than those given infusional 5-FU and had a comparable quality of life. These randomized trials demonstrate an evolution in our understanding of the clinical utility of irinotecan.
authors.affiliation: University of Texas, M.D. Anderson Cancer Center, Houston, USA.
authors.forename: R
authors.initials: R
authors.lastname: Pazdur
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D017326:Clinical Trials, Phase III as Topic; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005472:Fluorouracil / Q000627:therapeutic use; D005500:Follow-Up Studies; D006801:Humans; D000077146:Irinotecan; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic
chemical_list: D000964:Antimetabolites, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D000077146:Irinotecan; D005472:Fluorouracil; D002166:Camptothecin