Topotecan preceded by oxaliplatin using a 3 week schedule: a phase I study in advanced cancer patients.

摘要: Combinations of topoisomerase I (topo I) poisons and platinum derivatives have synergistic antitumoral effects. However, their clinical development is limited by supra-additive haematological toxicity. The aim this study was to determine whether sustained doses topotecan oxaliplatin could be achieved using a sequence. 34 advanced cancer patients 186 cycles were evaluable for toxicity over five dosing levels. Oxaliplatin at 85-110 mg/m(2) given on day 1, followed 0.5-1.25 mg/m(2)/day x 5 from 1 5, every 3 weeks. Plasma pharmacokinetics (PK) total ultrafiltrable platinum, lactone forms determined in the first cycle. dose-limiting (DT) identified as grade 4 thrombocytopenia. occurrence thrombocytopenia did not correlate with PK, but it patient's characteristics. Severe seen 1/8 without or biological evidence malnutrition, creatinine clearance higher than ml/s, no more two previous chemotherapy regimens, while 8/10 one these characteristics (P<0.004). In conclusion, recommended 110 mg/m(2)/day, weeks can administered favourable general status pretreatment phase II worthwhile ovarian patients.