Temozolomide and cisplatin versus temozolomide in patients with advanced melanoma: a randomized phase II study of the Hellenic Cooperative Oncology Group.

PURPOSE: Temozolomide (TMZ) is an oral alkylating agent that produces methyl adducts at the 0.6 position of guanine. The methyl adducts are removed by the DNA repair enzyme AGAT. As demonstrated by in vitro studies, cisplatin (CDDP) is able to down-regulate the AGAT activity, suggesting that CDDP could enhance the antitumor activity of TMZ. We designed a randomized phase II study to evaluate and compare the activity and safety profile of the combination versus single-agent TMZ in patients with advanced melanoma. PATIENTS AND METHODS: From January 2000 to April 2002, 132 patients were enrolled on the study. Patient and tumor characteristics were well balanced between the two arms. Patients with cerebral metastases were included. Patients received TMZ 200 mg/m(2)/day orally for five consecutive days every 4 weeks or TMZ + CDDP 200 mg/m(2) daily on days 1-5 and 75 mg/m(2) of CDDP on day 1. RESULTS: Tumor responses (complete and partial responses) were seen in 16 patients (26%) in arm A and 19 patients (29%) in arm B. The median time to progression (TTP) was 3.8 months in arm A and 5.8 months in arm B. The median overall survival (OS) was 11.5 months in arm A and 12 months in arm B. The difference between treatment arms regarding objective response rates, TTP and OS were not statistically significant. Toxicity was comparable between the two arms for anemia, leukopenia, neutropenia, thrombocytopenia, fatigue, constipation and arthralgias/myalgias. There was significantly more grade 3 and 4 emesis in the combination arm. CONCLUSIONS: No clear benefit in terms of response rates, median TTP or OS was shown with the combination of TMZ + CDDP. Additionally, the combination was associated with higher incidence of grade 3 and 4 emesis.

Chemotherapy with methotrexate, vinblastine, epirubicin and carboplatin (Carbo-MVE) in transitional cell urothelial cancer. A Hellenic Co-Operative Oncology Group study.

OBJECTIVES: We conducted a phase II study in order to assess the efficacy and toxicity of Carbo-MVE (carboplatin 250 mg/m2 i.v. day 1, methotrexate 25 mg/m2 i.v. days 1, 15 and 22, vinblastine 2.5 mg/m2 i.v. days 1, 15 and 22 and epirubicin 25 mg/m2 day 1). The regimen ws to be repeated every 28 days. METHODS: Forty-six patients with transitional cell carcinoma of the bladder entered the study. Patients with metastatic disease were treated for 6 cycles, while patients with locally advanced or locoregional disease had 4 cycles of induction chemotherapy followed by cystectomy or radiotherapy. RESULTS: Toxicity was generally mild and treatment well tolerated. The overall response rate was 54.4%, with 26% complete and 28.3% partial response rates. The median survival was 17.5 months with the complete responders to live significantly longer (64.82 months) than those who had a partial response (20.5 months), stable disease (15 months) or progressive disease (8.5 months). Survival was also significantly longer in patients with good performance status as well as in patients with locally advanced or locoregional disease. Finally, patients who had cystectomy as definitive treatment survived significantly longer (32 months) than those who had been irradiated (16 months). CONCLUSIONS: The Carbo-MVE regimen appears to be an effective and well-tolerated treatment in patients with transitional cell carcinoma of the bladder.