Dolastatin-10 in metastatic melanoma: A phase II and pharmokinetic trial of the California Cancer Consortium

Kim Margolin, Jeffrey Longmate, Timothy W. Synold, David R Gandara, Jeffrey Weber, Rene Gonzalez, Mary J. Johansen, Robert Newman, Tracey Baratta, James H. Doroshow

Research output: Contribution to journalArticle

67 Scopus citations

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 languageEnglish (US)
Pages (from-to)335-340
Number of pages6
JournalInvestigational New Drugs
Volume19
Issue number4
DOIs
StatePublished - 2001

Keywords

  • Dolastatin-10
  • Metastatic melanoma
  • Pharmokinetics

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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    Margolin, K., Longmate, J., Synold, T. W., Gandara, D. R., Weber, J., Gonzalez, R., Johansen, M. J., Newman, R., Baratta, T., & Doroshow, J. H. (2001). Dolastatin-10 in metastatic melanoma: A phase II and pharmokinetic trial of the California Cancer Consortium. Investigational New Drugs, 19(4), 335-340. https://doi.org/10.1023/A:1010626230081