A study of paclitaxel, carboplatin, and bortezomib in the treatment of metastatic malignant melanoma: A phase 2 consortium study

Gary A. Croghan, Vera J. Suman, William J. Maples, Mark Albertini, Gerald Linette, Lawrence Flaherty, John Eckardt, Cynthia Ma, Svetomir N. Markovic, Charles Erlichman

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24 Scopus citations

Abstract

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/m2 intravenously on Days 1, 4, and 8; paclitaxel at a dose of 175 mg/m2; 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.

Original languageEnglish
Pages (from-to)3463-3468
Number of pages6
JournalCancer
Volume116
Issue number14
DOIs
StatePublished - Jul 15 2010

Keywords

  • Bortezomib
  • Carboplatin
  • Metastatic melanoma
  • Paclitaxel

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    Croghan, G. A., Suman, V. J., Maples, W. J., Albertini, M., Linette, G., Flaherty, L., Eckardt, J., Ma, C., Markovic, S. N., & Erlichman, C. (2010). A study of paclitaxel, carboplatin, and bortezomib in the treatment of metastatic malignant melanoma: A phase 2 consortium study. Cancer, 116(14), 3463-3468. https://doi.org/10.1002/cncr.25191