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Dolastatin-10 in Metastatic Melanoma: A Phase II and Pharmokinetic Trial of the California Cancer Consortium

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Abstract

Dolastatin-10 is a novel pentapeptide agentoriginally isolated from the marine molluskDolabella auricularia with amechanism of antitumor activity thatinvolves the inhibition of microtubuleassembly. We performed a Phase II trial ofDolastatin-10, 400 μg/m2, inpatients with advanced melanoma who hadreceived no prior chemotherapy. Dolastatin-10 pharmokinetics wereevaluated in a subset of patients followingcourses 1 and 2. Twelve patients weretreated with a median of 2 cycles ofDolastatin-10, and no patient experiencedan objective response. The only grade >2toxicities were grade 3 neutropeniauncomplicated by infection, occurring in 4patients following the first treatmentcycle. The total systemic clearance andvolume of distribution at steady-state were2.61 ± 1.9 L/h/m2 and 28.4 ± 13 L/m2,respectively. Due toprolonged terminal elimination,Dolastatin-10 plasma concentrations ofgreater than 1 nM were sustained for 24h in all patients studied. Dolastatin-10 is unlikely to havesubstantial activity in the treatment ofmelanoma.

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Authors and Affiliations

  1. Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, Duarte, CA, U.S.A.

    Kim Margolin, Timothy W. Synold & James H. Doroshow

  2. Department of Biostatistics, City of Hope National Medical Center, Duarte, CA, U.S.A.

    Jeffrey Longmate & Tracey Baratta

  3. Department of Medical Oncology, University of California at Davis Medical Center, Sacramento, CA, U.S.A.

    David R. Gandara

  4. Department of Medical Oncology, University of Southern California/Kenneth Norris Cancer Center, Los Angeles, CA

    Jeffrey Weber

  5. Department of Medical Oncology, University of Colorado Cancer Center, Denver, CO, U.S.A.

    Rene Gonzalez

  6. Department of Experimental Therapeutics, M.D. Anderson Cancer Center, Houston, TX, U.S.A.

    Mary J. Johansen & Robert Newman

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  1. Kim Margolin
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Margolin, K., Longmate, J., Synold, T.W. et al. Dolastatin-10 in Metastatic Melanoma: A Phase II and Pharmokinetic Trial of the California Cancer Consortium. Invest New Drugs 19, 335–340 (2001). https://doi.org/10.1023/A:1010626230081

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