Cisplatin, etoposide, and ifosfamide salvage therapy for refractory or relapsing germ cell carcinoma.

Abstract

Thirty patients with metastatic progressive germ cell carcinoma who failed to be cured with first-line cisplatin chemotherapy were treated with a salvage regimen consisting of cisplatin 20 mg/m2, etoposide 100 mg/m2, and ifosfamide 1.2 g/m2 (PEI) intravenously (IV), days 1 to 5 every 3 weeks. Ten patients (33%) were tumor-free at the end of therapy. Complete response (CR) was achieved with chemotherapy alone in four patients and with additional surgery in six patients (two necroses, two mature teratomas, two carcinomas). Six patients (20%) had normalization of tumor markers but unresectable residual disease (Rm-), and the remaining 14 patients (46%) failed to respond. Of 10 patients with CR, nine (90%) relapsed again (eight carcinomas, one mature teratoma). The median duration of CR was 3.5 months. The median survival of the whole group was 311 days (range, 110 to 996+). Currently, seven of 30 patients are alive, and five of them are without signs of progressive tumor. The response to prior cisplatin therapy predicted for response and survival after PEI salvage therapy. Of 14 patients with prior CR, eight (57%) achieved a second CR compared with one of 11 (9%) with prior unfavorable response (P = .039). The median survival for patients with prior favorable response was 400 days, compared with 251 days for patients with prior unfavorable response (P less than .001). Myelosuppression was dose-limiting, with leukopenia greater than grade 2 in 84% and thrombocytopenia greater than grade 2 in 51% of all cycles. This three-drug regimen can induce a second CR in one third of patients with relapsed or refractory germ cell carcinoma. Only those patients with prior favorable responses can expect to be cured by this salvage regimen, while patients with prior unfavorable response should be considered for alternative salvage approaches.

Salvage treatment in male patients with germ cell tumours

“…The overall disease-free survival in our patients with malignant germ cell tumours relapsing after initial cisplatin-or carboplatin-based chemotherapy was thus only 27%, which is comparable to reported observations from other groups (Motzer et al, 1991;Harstrick et al, 1991). The results of third line treatment are even more dismal.…”

“…However, about 15% of all patients relapse after their initial treatment and need effective salvage treatment. The overall 5 years survival in these patients has been reported to be between 20 to 30% with no clear advantage of any salvage regimen (Motzer et al, 1991;Harstrick et al, 1991).…”

Prognosis after salvage treatment for unselected male patients with germ cell tumours

“…In agreement with other reports a CR to primary treatment was identified as most important predictor of favourable outcome of salvage treatment (Harstrick et al, 1991;Motzer et al, 1991;Pizzocaro et al, 1992;Droz et al, 1993). As described by several investigators the prognostic relevance of the relapse-free interval was substantiated by our study (Horwich et al, 1993;Josefsen et al, 1993;Steyerberg et al, 1993;Gerl et al, 1995), although it reached only borderline significance in our multivariate model.…”

“…disease-free long-term survival between 20% and 30% (Harstrick et al, 1991;Motzer et al, 1991;Josefsen et al, 1993;Einhorn et al, 1994). The 30% disease-free survival rate at a median follow-up of 90 months observed in our study is thus comparable to the results of other authors and stresses the need for continued investigation of potentially more efficacious salvage treatment.…”

Consolidative high-dose chemotherapy after conventional-dose chemotherapy as first salvage treatment for male patients with metastatic germ cell tumours

“…13 A few patients received vinblastine 0.11 mg/kg on days1 to 2 instead of etoposide (VeIP). 14 Treatment was given at the hospital to insure adequate hydration and mesna administration. Other routine supportive measures included antiemetic therapy, prophylaxis with granulocyte colony-stimulating factor (G-CSF), and packed red cell and platelet transfusions as necessary.…”