title: Phase II clinical trial of didemnin B in previously treated small cell lung cancer.
abstract: Didemnin B (NSC 325319), a cyclic depsipeptide isolated from a Carribean sea tunicate, exhibited potent antitumor activity in preclinical studies. After determining the maximum tolerated dose in our previous phase I/II trial, we conducted a phase II study of this drug in patients with previously treated small cell lung cancer; the starting dose was 6.3 mg/m2 intravenously over 30 min every 28 days. The major side effects were in the neuromuscular system and included severe muscle weakness, myopathy and/or myotonia by electromyography, and elevation of creatine phosphokinase and aldolase levels. We also observed modest increases in bilirubin and alkaline phosphatase levels. There were minimal hematologic toxic effects. No response was observed among 15 evaluable patients, leading us to conclude that didemnin B was toxic but inactive in patients with previously treated small cell lung cancer at the stated dose and schedule. A review of the literature revealed no significant antitumor activity in cancers of the colon, breast, ovaries, cervix, or lung (non-small cell) or in renal cell carcinoma. Further clinical trials for didemnin B may not be warranted at the stated dose and schedule.
authors.affiliation: Department of Thoracic/Head and Neck Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston.
authors.forename: D M
authors.initials: DM
authors.lastname: Shin
authors.forename: P Y
authors.initials: PY
authors.lastname: Holoye
authors.forename: A
authors.initials: A
authors.lastname: Forman
authors.forename: R
authors.initials: R
authors.lastname: Winn
authors.forename: R
authors.initials: R
authors.lastname: Perez-Soler
authors.forename: S
authors.initials: S
authors.lastname: Dakhil
authors.forename: J
authors.initials: J
authors.lastname: Rosenthal
authors.forename: M N
authors.initials: MN
authors.lastname: Raber
authors.forename: W K
authors.initials: WK
authors.lastname: Hong
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018288:Carcinoma, Small Cell / Q000188:drug therapy*; D002986:Clinical Trials as Topic; D003402:Creatine Kinase / Q000097:blood; D047630:Depsipeptides; D004576:Electromyography; D005260:Female; D005634:Fructose-Bisphosphate Aldolase / Q000097:blood; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D047630:Depsipeptides; D010456:Peptides, Cyclic; C030051:didemnins; D003402:Creatine Kinase; D005634:Fructose-Bisphosphate Aldolase