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

Cancer. 2010 Jul 15;116(14):3463-8. doi: 10.1002/cncr.25191.


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>or=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.

Publication types

  • Clinical Trial, Phase II
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Boronic Acids / administration & dosage
  • Bortezomib
  • Carboplatin / administration & dosage
  • Disease-Free Survival
  • Drug Administration Schedule
  • Early Termination of Clinical Trials
  • Female
  • Humans
  • Male
  • Melanoma / drug therapy*
  • Melanoma / mortality
  • Melanoma / pathology
  • Middle Aged
  • Neoplasm Metastasis
  • Paclitaxel / administration & dosage
  • Pyrazines / administration & dosage
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / mortality
  • Skin Neoplasms / pathology


  • Boronic Acids
  • Pyrazines
  • Bortezomib
  • Carboplatin
  • Paclitaxel