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Investigational New Drugs

, Volume 19, Issue 4, pp 335–340 | Cite as

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
Article

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.

Dolastatin-10 metastatic melanoma pharmokinetics 

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Copyright information

© Kluwer Academic Publishers 2001

Authors and Affiliations

  • Kim Margolin
    • 1
  • Jeffrey Longmate
    • 2
  • Timothy W. Synold
    • 1
  • David R. Gandara
    • 3
  • Jeffrey Weber
    • 4
  • Rene Gonzalez
    • 5
  • Mary J. Johansen
    • 6
  • Robert Newman
    • 6
  • Tracey Baratta
    • 2
  • James H. Doroshow
    • 1
  1. 1.Department of Medical Oncology and Therapeutics ResearchCity of Hope National Medical CenterDuarteU.S.A.
  2. 2.Department of BiostatisticsCity of Hope National Medical CenterDuarteU.S.A.
  3. 3.Department of Medical OncologyUniversity of California at Davis Medical CenterSacramentoU.S.A.
  4. 4.Department of Medical OncologyUniversity of Southern California/Kenneth Norris Cancer CenterLos Angeles
  5. 5.Department of Medical OncologyUniversity of Colorado Cancer CenterDenverU.S.A.
  6. 6.Department of Experimental TherapeuticsM.D. Anderson Cancer CenterHoustonU.S.A.

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