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Phase I trial of bortezomib and dacarbazine in melanoma and soft tissue sarcoma

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An Erratum to this article was published on 06 July 2013

Summary

Purpose Preclinical studies in human melanoma cell lines and murine xenograft tumor models suggest that the proteasome inhibitor bortezomib enhances the activity of the cytotoxic agent dacarbazine. We performed a phase I trial of bortezomib and dacarbazine in melanoma, soft tissue sarcoma, and amine precursor uptake and decarboxylation tumors. The primary objective was to identify recommended phase II doses for the combination. Experimental design Bortezomib and dacarbazine were both administered intravenously once weekly. All patients received prophylactic antiemetics. Dose escalation proceeded using a standard 3 + 3 design. Response was assessed according to NCI RECIST v1.0. Results Twenty eight patients were enrolled to six dose levels. Bortezomib 1.6 mg/m2 and dacarbazine 580 mg/m2 are the recommended phase II weekly doses. The combination was generally well tolerated. Among 15 patients with melanoma there was one durable complete response in a patient with an exon-11 cKIT mutation, and one partial response. Among 12 patients with soft tissue sarcoma there was one partial response. Conclusions Bortezomib 1.6 mg/m2 and dacarbazine 580 mg/m2 administered intravenously once weekly is well tolerated and has at least minimal activity in melanoma and soft tissue sarcoma.

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Acknowledgments

Supported in part by P30CA016059 (NCI), M01RR000065 (NCRR), and a grant from Millennium Pharmaceuticals, Inc.

Conflict of interest disclosures

The authors have no relevant conflicts to report.

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Authors and Affiliations

  1. Massey Cancer Center and the Division of Hematology, Oncology & Palliative Care, Virginia Commonwealth University, Richmond, VA, 23298-0037, USA

    Andrew Poklepovic & John D. Roberts

  2. School of Medicine, Virginia Commonwealth University, Richmond, VA, 23298-0037, USA

    Leena Youseffian

  3. Massey Cancer Center, Virginia Commonwealth University, Richmond, VA, 23298-0037, USA

    Mary Winning, Christine A. Birdsell & Viswanathan Ramakrishnan

  4. Norris Cotton Cancer, Geisel School of Medicine, Dartmouth Hitchcock Medical Center, Lebanon, NH, 03756, USA

    Nancy A. Crosby & Marc S. Ernstoff

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  1. Andrew Poklepovic
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  4. Christine A. Birdsell
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Correspondence to John D. Roberts.

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Poklepovic, A., Youseffian, L., Winning, M. et al. Phase I trial of bortezomib and dacarbazine in melanoma and soft tissue sarcoma. Invest New Drugs 31, 937–942 (2013). https://doi.org/10.1007/s10637-012-9913-8

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  • DOI: https://doi.org/10.1007/s10637-012-9913-8

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