• Poulam M Patel, Stefan Suciu, Laurent Mortier, Wim H Kruit, Caroline Robert, Dirk Schadendorf, Uwe Trefzer, Cornelis J A Punt, Reinhard Dummer, Neville Davidson, Juergen Becker, Robert Conry, John A Thompson, Wen-Jen Hwu, Kristel Engelen, Sanjiv S Agarwala, Ulrich Keilholz, Alexander M M Eggermont, Alain Spatz, and EORTC Melanoma Group.
• Academic Unit of Clinical Oncology, University of Nottingham, Nottingham, United Kingdom. poulam.patel@nottingham.ac.uk
• Eur. J. Cancer. 2011 Jul 1; 47 (10): 1476-83.

PurposeTo compare the efficacy of an extended schedule escalated dose of temozolomide versus standard dose dacarbazine in a large population of patients with stage IV melanoma.Patients And MethodsA total of 859 patients were randomised to receive oral temozolomide at 150 mg/m(2)/day for seven consecutive days every 2 weeks or dacarbazine, administered as an intravenous infusion at 1000 mg/m(2)/day on day 1 every 3 weeks. The primary endpoint was overall survival (OS), using an intent-to-treat principle. EudraCT number 2004-000654-23 NCI registration number NCT00005052.ResultsMedian OS was 9.1 months in the temozolomide arm and 9.4 months in the dacarbazine arm, with a hazard ratio (HR) of 1.00 (95%confidence interval [CI]: 0.86, 1.17; P=0.99). Median progression-free survival (PFS) was 2.3 months in the temozolomide arm and 2.2 months in the dacarbazine arm, with a HR of 0.92 (95%CI: 0.80, 1.06; P=0.27). In patients with measurable disease, overall response rate was higher in the temozolomide arm than in the dacarbazine arm (14.5% versus 9.8%, respectively), but the median duration of response was longer for dacarbazine. The extended schedule, escalated dose temozolomide arm showed more toxicity than the standard dose, single agent dacarbazine arm. The most common non-haematological treatment emergent adverse events reported in both treatment arms were nausea, fatigue and vomiting and constipation.ConclusionExtended schedule escalated dose Temozolomide (7 days on 7 days off) is feasible and has an acceptable safety profile, but does not improve OS and PFS in metastatic melanoma when compared to standard dose dacarbazine.Copyright © 2011 Elsevier Ltd. All rights reserved.

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