title: Phase II clinical and pharmacological study of didemnin B in patients with metastatic breast cancer.
abstract: Sixteen evaluable patients with metastatic breast cancer were entered into a phase II trial of didemnin B. They received the drug at an initial dose of 5.6 mg/m2 every 21 to 28 days. Major toxicities noted were myalgia and nausea and vomiting while myelosuppression was mild. There were no complete responses; however, two minor responses were observed. The pharmacokinetics of didemnin B were studied in 10 patients who received the drug as 30 to 60 min i.v. infusions. A sensitive competitive inhibition enzyme immunoassay was used to quantitate didemnin B levels. Drug was observed to be rapidly cleared from plasma in a biphasic manner (t1/2 alpha = 0.12 hr, t1/2 beta = 4.8 hr). Although the assay could not identify the presence of specific metabolites, the increase of apparent didemnin B levels in plasma at later time points suggested the formation of unidentified metabolites which cross reacted with the antibody in the analytical procedure. In vitro experiments indicated that didemnin B was not bound to bovine serum albumin and only a minor portion (24%) of drug was found associated with red blood cells.
authors.affiliation: Department of Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston 77030.
authors.forename: J A
authors.initials: JA
authors.lastname: Benvenuto
authors.forename: R A
authors.initials: RA
authors.lastname: Newman
authors.forename: G S
authors.initials: GS
authors.lastname: Bignami
authors.forename: T J
authors.initials: TJ
authors.lastname: Raybould
authors.forename: M N
authors.initials: MN
authors.lastname: Raber
authors.forename: L
authors.initials: L
authors.lastname: Esparza
authors.forename: R S
authors.initials: RS
authors.lastname: Walters
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D047630:Depsipeptides; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D007262:Infusions, Intravenous; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010456:Peptides, Cyclic / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D012044:Regression Analysis; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D047630:Depsipeptides; D010456:Peptides, Cyclic; C030051:didemnins