Cisplatin (C), temozolomide (T) every 21 days and concomitant thalidomide (TH) in patients (PTS) with malignant gliomas. Final results of a phase I study.

1554 Background - Pre-clinical evidence shows synergism between C and T because of higher inhibition of O6-methylguanine-DNA methyl-transferase, enzyme involved in the miss-match repair system. T is active against malignant gliomas and Th is emerging as an inhibitor of angiogenesis. PTS - 14 : 11 Glioblastomas (GB), 2 Anaplastic Astrocytomas grade 3 (AA) and 1 Anaplastic meningo-sarcoma (AMS); 9 male; median age 56.2(range 34.3-74.7). ECOG PS/#PTS: 0/3; 1/5; 2/5; 3/1. Eight PTS with GB had previous surgery, 10 had radiotherapy and PTS with AA and AMS had both. Methods - See table. All Pts received i.v. C 75 mg/m d1 and oral T at escalating dose starting from 100 mg/m orally dd1-5, every 21 days. By level 3 Pts received orally TH starting from 50mg total day dose continuously. Haematological toxicity was assessed the day before next cycle. Results - See table. A total of 64 cycles were delivered; 12 cycles were delayed by a week because of WBC/PLT g3 reduction. All 14 PTS were valuable for toxicity. WHO G1-2 tox was(type/#PTS): anemia/9; nausea/6; vomiting/4; allergic/4 (Cutaneus/3 and Dyspnoea/1, only PTS receiving TH); fatigue/3; uditive/2; epigastralgia/2; thrombocytopenia/2; granulocytopenia/2; artralgia/1; myalgia/1; somnolence/1;. WHO G 3-4 tox was: granulocytopenia/6 (febrile G4/1); vascular venous/3 (DVT/2 and PE/1, only PTS receiving TH); thrombocytopenia/1. All 11 PTS with GB are valuable for RR: 1 PR; 6 SD; 4 PD. Eight out of 11 PTS were valuable for TTP and OS: median TTP=3.5 mos (range 0.9-6.3); median OS=12.6 mos (range 2.8-24.9). A Pt with GB who gained PR has a PFS of 5.4+ mos. Two of 3 PTS with AA III has been treated in adjuvant setting and had respectively a TTP of 5.2 and a PFS of 23.9+ mos.,level 2 C and T every 21 days is feseable and safe as well as level 4 concomitant TH. A level 4 fase II study is ongoing. [Figure: see text] No significant financial relationships to disclose.