High dose chemotherapy with ifosfamide, carboplatin, and etoposide combined with autologous bone marrow transplantation for the treatment of poor-prognosis germ cell tumors and metastatic trophoblastic disease in adults

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Abstract
Background. A Phase I—II trial to assess the toxicity and efficacy of a tandem high dose chemotherapy combining ifosfamide, carboplatin, and etoposide in germ cell tumors and metastatic trophoblastic disease was performed. Methods. Thirty‐nine patients, with a total of 22 testicular tumors, 9 extragonadal germ cell tumors, 3 ovarian germ cell tumors, and 5 cases of metastatic trophoblastic disease, received tandem high dose therapy combining ifosfamide (7500‐12,500 mg/m2), carboplatin (875‐1225 mg/m2), and etoposide (1000‐1250 mg/m2), followed by bone marrow reinfusion. Among the 39 patients, 33 were refractory to cisplatin‐ or carboplatin‐based regimen and the response of 37 could be evaluated; 69 cycles of this tandem high dose therapy were administered. Results. The overall response rate was 46%, including a complete response (CR) rate of 35%. Of 21 patients with testicular tumors who could be evaluated, 10 (47%) achieved a CR. No CRs were obtained in patients with refractory extragonadal germ cell tumors. Nine partial responders after the first cycle became complete responders after the second. Nine (23%) of the patients were long term survivors (> 18 months), 7 of them in continuous CR. Side effects primarily were renal toxicity and entero‐colitis. Seven patients (18%) died of therapy‐related causes. The therapeutic contribution of ifosfamide must be explored and the maximum tolerated doses of this three‐drug regimen remain to be determined. Conclusion. This tandem therapeutic regimen is able to overcome resistance to a platinum‐based regimen in highly refractory germ cell tumors and gestational trophoblastic disease and to cure a number of patients. Cancer 1995; 75:874—85.