Dolastatin-10 in metastatic melanoma: a phase II and pharmokinetic trial of the California Cancer Consortium.
Dolastatin-10 is a novel pentapeptide agent originally isolated from the marine mollusk Dolabella auricularia with a mechanism of antitumor activity that involves the inhibition of microtubule assembly. We performed a Phase II trial of Dolastatin-10, 400 microg/m2 in patients with advanced melanoma who had received no prior chemotherapy. Dolastatin-10 pharmokinetics were evaluated in a subset of patients following courses 1 and 2. Twelve patients were treated with a median of 2 cycles of Dolastatin-10, and no patient experienced an objective response. The only grade >2 toxicities were grade 3 neutropenia uncomplicated by infection, occurring in 4 patients following the first treatment cycle. The total systemic clearance and volume of distribution at steady-state were 2.61 +/- 1.9 L/h/m2 and 28.4 +/- 13 L/m2, respectively. Due to prolonged terminal elimination. Dolastatin-10 plasma concentrations of greater than 1 nM were sustained for 24 h in all patients studied. Dolastatin-10 is unlikely to have substantial activity in the treatment of melanoma.
Margolin
K
K
Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, Duarte, CA 91010, USA. kmargolin@coh.org
Longmate
J
J
Synold
T W
TW
Gandara
D R
DR
Weber
J
J
Gonzalez
R
R
Johansen
M J
MJ
Newman
R
R
Baratta
T
T
Doroshow
J H
JH
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D002140:California; D047630:Depsipeptides; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009842:Oligopeptides / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000378:metabolism
D000970:Antineoplastic Agents; D047630:Depsipeptides; D009842:Oligopeptides; C064570:dolastatin 10