High-dose mitoxantrone and cyclophosphamide without stem cell support in high-risk and advanced solid tumors: a phase I trial

This phase I study was designed to develop a high-dose combination of two c ycles of mitoxantrone and cyclophosphamide in patients with solid tumors, a s an alternative to single-cycle high-dose regimens that use only alkylatin g agents. Treatment was delivered with granulocyte colony-stimulating facto r (G-CSF), but without stem cell support, in order to avoid potential tumor cell reinfusion, Thirty-one patients with advanced solid tumors received t wo cycles of high-dose mitoxantrone (20-30 mg/m(2)) plus high-dose cyclopho sphamide (3000-4000 mg/m(2)), All patients received G-CSF until hematologic recovery. Dose-escalation was performed when less than 50% of cycles per l evel had dose-limiting toxicity (DLT), The maximum tolerated dose (MTD) ach ieved was mitoxantrone 25 mg/m(2) and cyclophosphamide 4000 mg/m(2). Main d ose-limiting toxicities (DLTs) were hematological: grade IV neutropenia las ting more than 7 days and thrombopenia below 20 x 10(9)/l requiring more th an one platelet transfusion. Non-hematological DLT consisted predominantly of grade III emesis and asthenia, Follow-up after each cycle was performed in an outpatient setting and there were no toxic deaths. In conclusion, the administration of two cycles of high-dose mitoxantrone and cyclophosphamid e with G-CSF support is safe and feasible. MTD was mitoxantrone 25 mg/m(2) and cyclophosphamide 4000 mg/m(2). Evaluation of this regimen is being done in a phase II trial.