title: A phase II trial of irinotecan in hormone-refractory prostate cancer.
abstract: Irinotecan is a DNA topoisomerase I inhibitor that has a wide spectrum of activity against human tumors in both preclinical and clinical studies. To evaluate the efficacy of irinotecan in hormone-refractory prostate cancer, we conducted a phase II study in 15 men with metastatic, PSA-progressive disease after primary androgen deprivation. Irinotecan was administered at a dose of 125 mg/m2 weekly for four weeks followed by a two-week rest period; cycles were repeated every six weeks. Response was assessed by evaluation of serial changes in the serum PSA. None of fifteen patients had a decline in PSA of greater than 50%; eight patients had stable disease as a best response. None of three patients with measurable disease had a partial or complete response. Toxicity was primarily hematologic and gastrointestinal, with 40% of patients requiring dose modification due to granulocytopenia and 20% requiring intravenous fluid supplementation after development of diarrhea. There were no treatment-related deaths. We conclude that irinotecan in the dose and schedule used in this trial does not have significant activity against hormone-refractory prostate cancer.
authors.affiliation: Division of Hematology-Oncology and Jonsson Comprehensive Cancer Center, UCLA School of Medicine, Los Angeles, CA, USA. dreese@itsa.ucsf.edu
authors.forename: D M
authors.initials: DM
authors.lastname: Reese
authors.forename: S
authors.initials: S
authors.lastname: Tchekmedyian
authors.forename: Y
authors.initials: Y
authors.lastname: Chapman
authors.forename: D
authors.initials: D
authors.lastname: Prager
authors.forename: P J
authors.initials: PJ
authors.lastname: Rosen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000188:drug therapy*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D000077146:Irinotecan; D017430:Prostate-Specific Antigen; D002166:Camptothecin