Feasibility and toxicity study of a high-dose chemotherapy regimen for autotransplantation incorporating carboplatin, cyclophosphamide and thiotepa

Abstract

Sixteen patients received a high-dose chemotherapy regimen consisting of carboplatin (1600 mg/m2) and cyclophosphamide (6000 mg/m2) as daily two-hour infusions over four days (CC). All but two of them also received thiotepa (480 mg/m2) in eight 30-minute infusions given every 12 hours (CTC). Bone marrow and/or peripheral stem cell (PSC) reinfusions took place 72 hours after the last course of chemotherapy. The major toxicity was bone marrow suppression, the duration of which was markedly reduced in the patients receiving PSC reinfusions. Non-hematological toxicity was relatively mild and consisted of nausea and vomiting, minor mucositis and skin rashes. All but one patient had mild and completely reversible elevations of serum ALAT and/or LDH levels. One patient, who had received full-dose chemotherapy despite a creatinine clearance of 56 ml/min, developed significant toxicity consisting of transient cyclophosphamide-associated pancarditis, reversible neurotoxicity and partially reversible hearing loss and renal function impairment. There were no toxic deaths. In view of the high carboplatin dose, the CTC regimen may be particularly suitable for use in the salvage treatment of germ cell cancer. Since CTC causes no serious organ toxicity, further studies to determine its suitability for double or even triple transplantation programs are warranted.