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

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

Research output: Contribution to journalArticle

22 Citations (Scopus)

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

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Carboplatin
Paclitaxel
Melanoma
Therapeutics
Leukopenia
Neutropenia
Clinical Trials
Bortezomib
Drug Therapy
Survival
National Cancer Institute (U.S.)
Arthralgia
Drug Combinations
Platinum
Pulmonary Embolism
varespladib methyl
Terminology
Thrombocytopenia
Disease-Free Survival
Neoplasms

Keywords

  • Bortezomib
  • Carboplatin
  • Metastatic melanoma
  • Paclitaxel

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Croghan, G. A., Suman, V. J., Maples, W. J., Albertini, M., Linette, G., Flaherty, L., ... 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

A study of paclitaxel, carboplatin, and bortezomib in the treatment of metastatic malignant melanoma : A phase 2 consortium study. / Croghan, Gary A.; Suman, Vera Jean; Maples, William J.; Albertini, Mark; Linette, Gerald; Flaherty, Lawrence; Eckardt, John; Ma, Cynthia; Markovic, Svetomir Nenad; Erlichman, Charles.

In: Cancer, Vol. 116, No. 14, 15.07.2010, p. 3463-3468.

Research output: Contribution to journalArticle

Croghan, GA, Suman, VJ, Maples, WJ, Albertini, M, Linette, G, Flaherty, L, Eckardt, J, Ma, C, Markovic, SN & Erlichman, C 2010, 'A study of paclitaxel, carboplatin, and bortezomib in the treatment of metastatic malignant melanoma: A phase 2 consortium study', Cancer, vol. 116, no. 14, pp. 3463-3468. https://doi.org/10.1002/cncr.25191
Croghan, Gary A. ; Suman, Vera Jean ; Maples, William J. ; Albertini, Mark ; Linette, Gerald ; Flaherty, Lawrence ; Eckardt, John ; Ma, Cynthia ; Markovic, Svetomir Nenad ; Erlichman, Charles. / A study of paclitaxel, carboplatin, and bortezomib in the treatment of metastatic malignant melanoma : A phase 2 consortium study. In: Cancer. 2010 ; Vol. 116, No. 14. pp. 3463-3468.
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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.",
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