Document Detail

Phase I trial of bortezomib and dacarbazine in melanoma and soft tissue sarcoma.
MedLine Citation:
PMID:  23315028     Owner:  NLM     Status:  Publisher    
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/m(2) and dacarbazine 580 mg/m(2) 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/m(2) and dacarbazine 580 mg/m(2) administered intravenously once weekly is well tolerated and has at least minimal activity in melanoma and soft tissue sarcoma.
Andrew Poklepovic; Leena Youseffian; Mary Winning; Christine A Birdsell; Nancy A Crosby; Viswanathan Ramakrishnan; Marc S Ernstoff; John D Roberts
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-13
Journal Detail:
Title:  Investigational new drugs     Volume:  -     ISSN:  1573-0646     ISO Abbreviation:  Invest New Drugs     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-14     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8309330     Medline TA:  Invest New Drugs     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Massey Cancer Center and the Division of Hematology, Oncology & Palliative Care, Virginia Commonwealth University, Richmond, VA, 23298-0037, USA.
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