Extended schedule, escalated dose temozolomide versus dacarbazine in stage IV melanoma: Final results of a randomised phase III study (EORTC 18032)

• DOI: 10.1016/j.ejca.2011.04.030
• Publication Date: 2011-05-23T22:22:06Z
• Authors: 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. Eg...; Alain Spatz
• Keywords: Male; 0301 basic medicine; Skin Neoplasms; Time Factors; Medizin; 610 Medicine & health; Drug Administration Schedule; 03 medical and health sciences; 0302 clinical medicine; Temozolomide; Humans; 1306 Cancer Research; Infusions, Intravenous; Melanoma; Aged; Neoplasm Staging; Remission Induction; 10177 Dermatology Clinic; Middle Aged; 3. Good health; Dacarbazine; ONCOL 3: Translational research; EMC MM-03-86-08; Area Under Curve; EMC MM-03-47-11; 2730 Oncology; Female; Safety

To 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.A 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.Median 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.Extended 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.