Dolastatin-10 in metastatic melanoma: a phase II and pharmokinetic trial of the California Cancer Consortium |
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| Authors: | Margolin K Longmate J Synold T W Gandara D R Weber J Gonzalez R Johansen M J Newman R Baratta T Doroshow J H |
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| Affiliation: | (1) Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, Duarte, CA, U.S.A.;(2) Department of Biostatistics, City of Hope National Medical Center, Duarte, CA, U.S.A.;(3) Department of Medical Oncology, University of California at Davis Medical Center, Sacramento, CA, U.S.A.;(4) Department of Medical Oncology, University of Southern California/Kenneth Norris Cancer Center, Los Angeles, CA;(5) Department of Medical Oncology, University of Colorado Cancer Center, Denver, CO, U.S.A.;(6) Department of Experimental Therapeutics, M.D. Anderson Cancer Center, Houston, TX, U.S.A. |
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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  g/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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| Keywords: | Dolastatin-10 metastatic melanoma pharmokinetics |
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