A phase II study of extended dose temozolomide and thalidomide in previously treated patients with metastatic melanoma.

PURPOSE: To assess the efficacy and tolerability of extended dose temozolomide and continuous thalidomide in patients with advanced metastatic cutaneous melanoma. PATIENTS AND METHODS: Eligibility criteria included adults with histologic diagnosis of metastatic melanoma with adequate organ function and performance status. Temozolomide (75 mg/m(2)/day) was administered for 6 weeks followed by a 2-week rest. Thalidomide (200 mg/day) was given for the first 2 weeks and increased by 100 mg/day at weekly intervals up to a maximum of 400 mg/day, if no toxicity. For patients older than 70 years, thalidomide was started at 100 mg/day and the dose was increased by 50 mg/day up to a maximum of 250 mg/day. RESULTS: Twenty-six extensively pretreated subjects, with poor prognostic factors, were entered into this study and included in all analyses. According to the RECIST criteria, one (4%) subject achieved a complete response (CR), two (8%) partial response (PR), and five (19%) stable disease (SD), for a response rate (CR + PR) of 12% [95% confidence interval (CI), 0-24.7%] and a clinical benefit (CR + PR + SD) of 31%. Median time to progression was 1.8 months (95% CI, 1.2-2.4 months) and median survival was 5.2 months (95% CI, 4.1-6.2 months). CONCLUSIONS: The combination of temozolomide and thalidomide is well tolerated in patients with very advanced heavily pretreated metastatic melanoma. It has modest activity in this population with grave prognosis.

A phase I study of thalidomide, capecitabine and temozolomide in advanced cancer.

AIM: To develop a novel oral antiangiogenic and immunomodulatory chemotherapy regimen against advanced cancers. METHODS: Patients were enrolled in cohorts of three or six in a standard phase I design. Thalidomide 100 mg was kept stable for all cohorts. If well tolerated after one week, capecitabine and temozolomide (TCT) fixed-dose were given daily without rest and escalated one at a time until dose limiting toxicity (DLT) occurred. If no DLT occurred within 28 days (1 cycle), the subsequent group was enrolled into the next dose level. RESULTS: Twenty-three adult patients with objective documentation of progressive metastatic cancer after a median of two therapies (range 0-4) received TCT in this study. Based on DLT within the first 28 days, the MTD of daily TCT therapy was thalidomide 100 mg, capecitabine 2000 mg and temozolomide 100 mg. With long-term treatment, majority of the patients required dose interruptions due to fatigue, hand-foot syndrome, and neutropenia. A dose level consisting of daily thalidomide and three-weeks-on one-week-off capecitabine and temozolomide was implemented and administered to six patients without DLT. Out of 23 subjects, four (17%) achieved a partial response (renal, gastric, prostate 2), and four patients (17%) had stable disease (renal, colon, pancreas 2), adding to a clinical benefit of 34%. CONCLUSIONS: TCT is an effective palliative oral chemo-immunotherapy for patients with advanced cancer. The recommended dose for phase II trial is thalidomide 100 mg daily without a break, capecitabine 2000 mg and temozolomide 100 mg daily three-weeks on and one-week off.