Phase II clinical and pharmacological study of didemnin B in patients with metastatic breast cancer

Summary

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 (t 1/2α=0.12 hr, t 1/2β=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.