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A study of paclitaxel, carboplatin, and bortezomib in the treatment of metastatic malignant melanoma
Author(s) -
Croghan Gary A.,
Suman Vera J.,
Maples William J.,
Albertini Mark,
Linette Gerald,
Flaherty Lawrence,
Eckardt John,
Ma Cynthia,
Markovic Svetomir N.,
Erlichman Charles
Publication year - 2010
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.25191
Subject(s) - medicine , leukopenia , neutropenia , carboplatin , bortezomib , common terminology criteria for adverse events , chemotherapy , clinical endpoint , oncology , paclitaxel , phases of clinical research , febrile neutropenia , response evaluation criteria in solid tumors , adverse effect , gastroenterology , surgery , clinical trial , multiple myeloma , cisplatin
BACKGROUND: Chemotherapy has not been reported to have a significant impact on survival for patients with metastatic melanoma. Bortezomib was shown to have additive/synergistic effects with several chemotherapeutic agents, including paclitaxel and platinum. A phase 1 trial of this 3‐drug combination reported that 6 of 28 patients treated with bortezomib followed by paclitaxel and carboplatin achieved a partial response (including 2 of 5 patients with metastatic melanoma). METHODS: A 2‐stage phase 2 clinical trial was conducted to assess the antitumor activity of this 3‐agent combination in patients with metastatic melanoma who had received at most 1 prior chemotherapy for metastatic disease. Treatment included bortezomib at a dose of 1.3 mg/m 2 intravenously on Days 1, 4, and 8; paclitaxel at a dose of 175 mg/m 2 ; and carboplatin at an area under the concentration (AUC) of 6 on Day 2 of a 21‐day cycle. The primary endpoint of this trial was tumor response rate (TRR). RESULTS: Seventeen eligible patients were enrolled. A median of 4 cycles were administered (range, 1‐7 cycles). Three patients discontinued treatment due to persistent grade 4 (based on National Cancer Institute Common Terminology Criteria for Adverse Events [version 3.0]) neutropenia with grade 3 leukopenia (2 patients) or grade 4 pulmonary embolism (1 patient). Grade ≥3 toxicities included neutropenia (71%), leukopenia (41%), thrombocytopenia (29%), and arthralgia (12%). Two partial responses were observed (TRR, 11.8%). Four patients had stable disease at >12 weeks. The median progression‐free survival was 3.2 months, and the median overall survival was 7.0 months. CONCLUSIONS: Due to insufficient clinical efficacy, this trial did not proceed to second‐stage accrual. The combination of paclitaxel, carboplatin, and bortezomib demonstrated limited clinical benefit and was associated with significant toxicity. Cancer 2010. © 2010 American Cancer Society.