Original Article

You have full text access to this OnlineOpen article

Phase 2 trial of combination thalidomide plus temozolomide in patients with metastatic malignant melanoma: Southwest Oncology Group S0508†

  1. Joseph I. Clark MD1,‡,*,
  2. James Moon MS2,
  3. Laura F. Hutchins MD3,
  4. Jeffrey A. Sosman MD4,
  5. W. Martin Kast PhD5,
  6. Diane M. Da Silva PhD5,
  7. P. Y. Liu PhD2,
  8. John A. Thompson MD6,
  9. Lawrence E. Flaherty MD7,
  10. Vernon K. Sondak MD8

Article first published online: 13 NOV 2009

DOI: 10.1002/cncr.24739

Issue

Cancer

Cancer

Volume 116, Issue 2, pages 424–431, 15 January 2010

Additional Information

How to Cite

Clark, J. I., Moon, J., Hutchins, L. F., Sosman, J. A., Kast, W. M., Da Silva, D. M., Liu, P. Y., Thompson, J. A., Flaherty, L. E. and Sondak, V. K. (2010), Phase 2 trial of combination thalidomide plus temozolomide in patients with metastatic malignant melanoma: Southwest Oncology Group S0508. Cancer, 116: 424–431. doi: 10.1002/cncr.24739

Author Information

  1. 1

    Loyola University Stritch School of Medicine, Maywood, Illinois

  2. 2

    Southwest Oncology Group Statistical Center, Seattle, Washington

  3. 3

    University of Arkansas for Medical Sciences, Little Rock, Arkansas

  4. 4

    Vanderbilt University School of Medicine, Nashville, Tennessee

  5. 5

    University of Southern California, Los Angeles, California

  6. 6

    Seattle Cancer Care Alliance, Seattle, Washington

  7. 7

    Wayne State University, Detroit, Michigan

  8. 8

    H. Lee Moffitt Cancer Center, Tampa, Florida

  1. ‡

    Fax: (708) 327-3218

*Cardinal Bernardin Cancer Center, Loyola University Medical Center, Division of Hematology/Oncology, 2160 South First Avenue, Maywood, IL 60153

  1. †

    Presented at the American Society of Clinical Oncology (ASCO) 44th Annual Meeting , May 30–June 3, 2008, Chicago, Illinois.

Publication History

  1. Issue published online: 20 JAN 2010
  2. Article first published online: 13 NOV 2009
  3. Manuscript Accepted: 4 MAY 2009
  4. Manuscript Revised: 16 APR 2009
  5. Manuscript Received: 6 FEB 2009

Funded by

  • National Cancer Institute, DHHS. Grant Numbers: CA32102, CA38926, CA46282, CA20319, CA22433, CA35178, CA45807, CA35261, CA35176, CA35431, CA37981, CA74647, CA45808, CA58861, CA45461, CA04919, CA58416, CA67575, CA45560, CA76426, CA11083
  • Celgene Corporation

SEARCH

SEARCH BY CITATION

ARTICLE TOOLS

View Full Article (HTML) Get PDF (146K)

Keywords:

  • phase 2;
  • thalidomide and temozolomide;
  • Southwest Oncology Group

This combination of thalidomide and temozolomide does not appear to have a clinical benefit that exceeds dacarbazine alone. We would not recommend it further for phase 3 trials or for standard community use.

Abstract

BACKGROUND:

In limited institution phase 2 studies, thalidomide and temozolomide has yielded response rates (RRs) up to 32% for advanced melanoma, leading to the use of this combination as “standard” by some. We conducted a multicenter phase 2 trial to better define the clinical efficacy of thalidomide and temozolomide and the immune modulatory effects of thalidomide, when combined with temozolomide, in patients with metastatic melanoma.

METHODS:

Patients must have had stage IV cutaneous melanoma, no active brain metastases, Zubrod PS 0-1, up to 1 prior systemic therapy excluding thalidomide, temozolomide, or dacarbazine, adequate organ function, and given informed consent. The primary endpoint was 6-month progression-free survival (PFS). Secondary endpoints included overall survival (OS), RR, toxicities, and assessment of relationships between biomarkers and clinical outcomes. Patients received thalidomide (200 mg/d escalated to 400 mg/d for patients <70, or 100 mg/d escalated to 250 mg/d for patients ≥70) plus temozolomide (75 mg/m2/d × 6 weeks, and then 2 weeks rest).

RESULTS:

Sixty-four patients were enrolled; 2 refused treatment. The 6-month PFS was 15% (95% confidence interval [CI], 6%-23%), the 1-year OS was 35% (95% CI, 24%-47%), and the RR was 13% (95% CI, 5%-25%), all partial. One treatment-related death occurred from myocardial infarction; 3 other grade 4 events occurred, including pulmonary embolism, neutropenia, and central nervous system (CNS) ischemia. There was no significant correlation between biomarkers and PFS or OS.

CONCLUSIONS:

This combination of thalidomide and temozolomide does not appear to have a clinical benefit that exceeds dacarbazine alone. We would not recommend it further for phase 3 trials or for standard community use. Cancer 2010. © 2010 American Cancer Society.

View Full Article (HTML) Get PDF (146K)