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Investigational New Drugs
Published in: Investigational New Drugs 4/2013

01-08-2013 | PHASE I STUDIES

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

Authors: Andrew Poklepovic, Leena Youseffian, Mary Winning, Christine A. Birdsell, Nancy A. Crosby, Viswanathan Ramakrishnan, Marc S. Ernstoff, John D. Roberts

Published in: Investigational New Drugs | Issue 4/2013

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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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Metadata
Title
Phase I trial of bortezomib and dacarbazine in melanoma and soft tissue sarcoma
Authors
Andrew Poklepovic
Leena Youseffian
Mary Winning
Christine A. Birdsell
Nancy A. Crosby
Viswanathan Ramakrishnan
Marc S. Ernstoff
John D. Roberts
Publication date
01-08-2013
Publisher
Springer US
Published in
Investigational New Drugs / Issue 4/2013
Print ISSN: 0167-6997
Electronic ISSN: 1573-0646
DOI
https://doi.org/10.1007/s10637-012-9913-8

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