title: Phase I clinical study of didemnin B. A National Cancer Institute of Canada Clinical Trials Group study.
abstract: Didemnin B (NSC-325319), a new depsipeptide isolated from a Caribbean tunicate, has been evaluated in a clinical phase I study. The drug was administered in a schedule of a 4 weekly intravenous injection in a six-weeks cycle. Fifty-three patients received 71 evaluable cycles in an escalated dose ranging from 0.4 mg/m2/week to 2.5 mg/m2/week. No hematological toxicity was demonstrated at any dose level. Without prophylactic antiemetics nausea and vomiting was dose limiting at 1.2 mg/m2/week. Due to the use of Cremophor EL as a solvent, hypersensitivity reactions occurred in 9 patients. These reactions occurred following prior exposure to the drug and were commonly seen at the 3rd dose. They were not dose related but became more frequent at 1.5 mg/m2/week necessitating prophylactic treatment with H and H2 receptor blocking agents. Non-hematological toxicities included mild diarrhea, mucositis, anorexia, headaches, and local phlebitis. The dose- limiting toxicity was generalized weakness which became severe and disabling in 3 of 6 patients treated at 2.5 mg/m2/week. No objective responses were documented in 39 patients with evaluable disease. The recommended dose for phase II studies was 2.3 mg/m2/week x 4 in a 6-weeks cycle given with prophylactic antiemetics and H1 and H2 receptor blocking agents.
authors.affiliation: Ottawa Regional Cancer Centre, Ontario, Canada.
authors.forename: J A
authors.initials: JA
authors.lastname: Maroun
authors.forename: D
authors.initials: D
authors.lastname: Stewart
authors.forename: S
authors.initials: S
authors.lastname: Verma
authors.forename: E
authors.initials: E
authors.lastname: Eisenhauer
mesh_terms: D000328:Adult; D000368:Aged; D000932:Antiemetics / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D047630:Depsipeptides; D004342:Drug Hypersensitivity / Q000209:etiology; D005260:Female; D006098:Granulocytes / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced / Q000188:drug therapy; D009369:Neoplasms / Q000188:drug therapy*; D010456:Peptides, Cyclic / Q000009:adverse effects* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000932:Antiemetics; D000970:Antineoplastic Agents; D047630:Depsipeptides; D010456:Peptides, Cyclic; C030051:didemnins