Background: There is pre-clinical evidence of synergism between cisplatin (P) and temozolomide (T) due to higher inhibition by T of O6-alkyl- guanine-alkyltransferase (AGAT), an enzyme involved in the mismatch repair system. T and P are active against malignant gliomas while thalidomide (TH) is emerging as an inhibitor of angiogenesis. Patients and Methods: Triplets of patients with malignant brain tumors received escalating doses of P, T and TH up to the dose-limiting-toxicity (DLT) and the maximal tolerated dose (MTD). Results: Seventeen patients were enrolled and a total of 74 cycles were delivered. The MTD was P 75 mg/m2 day 1 and T 150 mg/m2 days 1 to 5 every 21 days with a concomitant 200 mg total daily dose of TH. DLT events were G4 thrombocytopenia and febrile neutropenia. Conclusion: Concomitant administration of P 75 mg/m2 day 1, T 150 mg/m2 days 1 to 5 every 21 days and concomitant TH at a total daily dose of 150 mg is feasible and safe. Early efficacy data are encouraging and a phase II study is ongoing.
|Number of pages||6|
|Publication status||Published - Mar 2007|
ASJC Scopus subject areas
- Cancer Research