Phase II clinical and pharmacological study of didemnin B in patients with metastatic breast cancer.
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.
Benvenuto
J A
JA
Department of Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Newman
R A
RA
Bignami
G S
GS
Raybould
T J
TJ
Raber
M N
MN
Esparza
L
L
Walters
R S
RS
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
D000970:Antineoplastic Agents; D047630:Depsipeptides; D010456:Peptides, Cyclic; C030051:didemnins