Continuous temozolomide (TMZ) monotherapy as first-line treatment in patients with metastatic melanoma (MM).

Abstract

e19030 Background: TMZ is a promising treatment option in MM. Phase I-II studies of first-line TMZ monotherapy have shown median overall survival (OS) of up to 13.1 months and progression-free survival (PFS) up to 1.9 months. We present the results of first- line continuous TMZ monotherapy in patients with MM. Methods: Retrospective analysis of patients with cutaneous MM and measurable lesions treated from 2000–2009. Patients could have previously received adjuvant interferon (IFN) or surgery as primary treatment. Exclusion criteria included any previous chemotherapy and ocular melanoma. Brain metastases were allowed. TMZ was administered under compassionate use at 200 mg/m2 days 1-5 every 28 days until progression or unacceptable toxicity. Outcomes included response as primary endpoint and, OS, PFS and toxicity as secondary endpoints. Results: A total of 36 patients were included: mean age 54 years (range 24-81); 95% ECOG performance status 0- 1; 17 patients had previous adjuvant high-dose IFN therapy. Prior to TMZ therapy the median number of metastases was 2.3 (range 1-5) and 6 patients had brain metastases. The mean number of TMZ cycles administered was 8.8 (range 1-53). Efficacy was not evaluated in 2 patients due to early death. The objective response rate was 19%, the complete response rate was 8% and stable disease was achieved in an additional 17% of patients. New brain metastases were observed in only 3 patients. Mean OS was 20.2 months (range 0.8-110.8) and median OS 9.3 months (95% CI 5.1- 13.5). Median PFS was 4.6 months (20 weeks 95% CI 14.4-25.0). At time of analysis, 6 patients were alive and 3 were disease-free; of these 2 continue to receive TMZ. TMZ had an acceptable toxicity profile; the most common toxicity was hematological (17% grade 1-2 and 22% grade 3- 4). Conclusions: First-line continuous TMZ monotherapy in patients with MM resulted in a median OS consistent with previous trials and a median PFS somewhat higher than previously seen. The toxicity profile was acceptable. The low number of patients developing brain metastases reflects the protective effect of TMZ against this type of disease progression. No significant financial relationships to disclose.