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 μg/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.
Original language | English (US) |
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Pages (from-to) | 335-340 |
Number of pages | 6 |
Journal | Investigational New Drugs |
Volume | 19 |
Issue number | 4 |
DOIs | |
State | Published - 2001 |
Keywords
- Dolastatin-10
- Metastatic melanoma
- Pharmokinetics
ASJC Scopus subject areas
- Molecular Medicine
- Pharmacology