High dose carboplatin/VP-16 plus ifosfamide with autologous bone marrow support in the treatment of refractory germ cell tumors

Abstract

We report seven patients with germ cell tumors which either recurred following a minimum of two regimens of platinum-based chemotherapy or were refractory to cisplatin. The patients were treated with one or two courses of high dose carboplatin (CBDCA) and etoposide (VP-16) plus ifosfamide (IFX) with mesna uroprotection and autologous bone marrow support. The doses given were CBDCA 500 mg/m2 every other day x 3 and VP-16 400 mg/m2 every other day x 3. IFX was given in a dose of 2 g/m2 daily x 5 days with mesna. The original intent of the protocol was to explore escalating doses of IFX, but excessive renal toxicity at the first dose level prevented escalation. Of the seven patients treated, four developed a marked decline in their renal function and three of the four required hemodialysis or hemofiltration. Six of seven patients treated had a decline in their serum markers indicating a response to therapy, but all have relapsed. Our conclusion is that while the combination of CBDCA/VP-16/IFX with ABMT is active in this group of patients, it is associated with excessive renal toxicity which is probably due to underlying renal dysfunction secondary to extensive prior cisplatin-based chemotherapy.