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Melanoma and Cutaneous Malignancies

Temozolomide for the Treatment of Metastatic Melanoma: A Systematic Review

^aPrincess Margaret Hospital, Toronto, Canada; ^bOttawa Hospital, Ottawa, Canada; ^cToronto Sunnybrook Regional Cancer Centre, Toronto, Canada; ^dCancer Care Ontario Program in Evidence-Based Care, McMaster University, Hamilton, Canada

Key Words. Melanoma • Temozolomide • Temodal • Chemotherapy • Systematic review

Correspondence: Ian Quirt, M.D., c/o Denise Stys-Norman, Cancer Care Ontario Program in Evidence-Based Care, McMaster University, 1280 Main Street West, DTC 3rd Floor, Hamilton, Ontario, Canada L8S 4L8. Telephone: 905-525-9140, ext. 22115; Fax: 905-522-7681; e-mail: stysnor{at}mcmaster.ca

Disclosure: No potential conflicts of interest were reported by the authors, planners, reviewers, or staff managers of this article.

Background. This systematic review examines the role of temozolomide in patients with metastatic melanoma. Outcomes of interest include response rate, progression-free survival, overall survival, quality of life, and adverse effects.

Methods. The MEDLINE, EMBASE, and Cochrane Library databases were searched from 1980 through to 2005 using variations on the search terms: melanoma, clinical trial, random, temozolomide, temodal, and temodar. The American Society of Clinical Oncology Annual Meeting proceedings were searched from 1996 to 2005. Relevant articles and abstracts were selected and reviewed by two reviewers, and the reference lists from these sources were searched for additional trials.

Results. Two randomized phase III trials and three randomized phase II trials were located. In addition, 21 phase I or II trials investigating single-agent temozolomide, temozolomide plus interferon-, and temozolomide plus thalidomide were reviewed. A direct comparison of temozolomide and dacarbazine demonstrated equal efficacy for response rates and overall survival; however, no significant difference was reported. A second phase III study comparing single-agent temozolomide with temozolomide combined with interferon- indicated a significantly higher response rate for the combination treatment arm, but no difference in overall survival was noted. Further phase III studies are required to confirm whether there is a benefit associated with the combination of temozolomide and interferon- or thalidomide.

Conclusion. Our review of the available literature suggests that temozolomide demonstrates comparable activity to the current standard treatment, dacarbazine, with the additional benefit of being a convenient oral treatment that penetrates the blood–brain barrier.

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