Temozolomide is a cytotoxic prodrug that, when hydrolyzed, inhibits DNA replication by methylating nucleotide bases. In preclinical testing, temozolomide has shown a broad spectrum of antineoplastic activity. In a randomized phase III trial involving patients with advanced malignant melanoma, temozolomide produced an objective response rate of 13.5% compared with 12.1% in the dacarbazine group. Temozolomide produced a modest increase in PFS time compared with dacarbazine (1.9 vs 1.5 months). There was a statistically significant difference in favor of the temozolomide-treated group in the physical functioning and cognitive functioning domains.
The guidelines support the proposed recommendation. It is reasonable to use temozolomide at a dose of 200 mg/m2 orally for five days every four weeks as initial systemic treatment for patients with unresectable metastatic malignant melanoma. It is listed by NCCN.
Quirt I, Verma S, Petrella T, Bak K, Charette M, Melanoma Disease Site Group. Temozolomide for the treatment of metastatic melanoma: a clinical practice guideline. Toronto (ON): Cancer Care Ontario (CCO); 2006 Mar 20. 25 p. (Evidence-based series; no. 8-4). [38 references]
Highlights of the NCCN 11th Annual Conference: Clinical Practice Guidelines & Quality Cancer Care™, published as a supplement to The Oncology Report by Elsevier Oncology. © 2006 NCCN.
Darkes M.J.M.; Plosker G.L.; Jarvis B. Temozolomide: A Review of its Use in the Treatment of Malignant Gliomas, Malignant Melanoma and Other Advanced Cancers American Journal of Cancer, Volume 1, Number 1, 1 January 2002, pp. 55-80(26)