| Literature DB >> 11561695 |
K Margolin1, J Longmate, T W Synold, D R Gandara, J Weber, R Gonzalez, M J Johansen, R Newman, T Baratta, J H Doroshow.
Abstract
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.Entities:
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Year: 2001 PMID： 11561695 DOI： 10.1023/a:1010626230081
Source DB: PubMed Journal: Invest New Drugs ISSN： 0167-6997 Impact factor: 3.850