title: Phase I trial of bortezomib and dacarbazine in melanoma and soft tissue sarcoma.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
authors: Massey Cancer Center and the Division of Hematology, Oncology & Palliative Care, Virginia Commonwealth University, Richmond, VA 23298-0037, USA.
authors: Andrew
authors: A
authors: Poklepovic
authors: Leena E
authors: LE
authors: Youssefian
authors: Leena
authors: L
authors: Youseffian
authors: Mary
authors: M
authors: Winning
authors: Christine A
authors: CA
authors: Birdsell
authors: Nancy A
authors: NA
authors: Crosby
authors: Viswanathan
authors: V
authors: Ramakrishnan
authors: Marc S
authors: MS
authors: Ernstoff
authors: John D
authors: JD
authors: Roberts
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001897:Boronic Acids / Q000009:adverse effects / Q000627:therapeutic use*; D000069286:Bortezomib; D003606:Dacarbazine / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000556:secondary; D008297:Male; D055118:Medication Adherence; D008545:Melanoma / Q000000981:diagnostic imaging / Q000188:drug therapy*; D008875:Middle Aged; D011719:Pyrazines / Q000009:adverse effects / Q000627:therapeutic use*; D011859:Radiography; D012509:Sarcoma / Q000188:drug therapy*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib; D003606:Dacarbazine