TREATMENT OF GERM-CELL CANCER WITH 2 CYCLES OF HIGH-DOSE IFOSFAMIDE, CARBOPLATIN, AND ETOPOSIDE WITH AUTOLOGOUS STEM-CELL SUPPORT

Purpose: To evaluate the activity of two cycles of high-dose ifosfamid e, carboplatin, and etoposide (ICE) with autologous hematopoietic prog enitor cell support (aHPCS) in patients with poor-prognosis, chemother apeutically sensitive germ cell cancer. Patients and Methods: Twenty p atients with germ cell tumor who had persistent disease or relapse fro m standard-risk or high-risk presentation were entered on this pilot s tudy. The entry criteria included relapsed gonadal and extragonadal ge rm cell cancer unlikely to be cured by standard salvage therapy but wi thout proven refractoriness to chemotherapy. Treatment consisted of tw o cycles of ICE chemotherapy with mesna uroprotection and aHPCS. On th e first cycle, ifosfamide (IFX), 2 gm/m(2); carboplatin, 400 mg/m(2); and etoposide, 20 mg/kg, were administered on days -6, -5, and -4. On the second cycle, the doses and schedule of carboplatin and etoposide were identical, and patients with normal renal function received addit ional IFX, 2 g/m(2) on day -3 and 1 g/m(2) on day -2. Mesna, 600 mg/m( 2) every 6 hours, was given until 24 hours following the final dose of IFX on each cycle, and autologous bone marrow and/or peripheral stem- cells were infused on day 0. Results: All twenty patients are assessab le for toxicity and current disease status. Two patients received only one cycle of therapy, one because of the development of active hepati tis C following cycle 1, and one because of renal insufficiency. No pa tient died as a result of protocol therapy, and no patient developed d ebilitating peripheral neuropathy, symptomatic hearing loss, or severe renal insufficiency requiring dialysis. The median time to recovery o f greater than or equal to 500 neutrophils/mu L and platelets greater than or equal to 50,000/mu L was day +11 and day +15, respectively. Th e median maximum creatinine was 1.6 mg/dL on each treatment cycle, and there was no other significant organ toxicity. With a median follow-u p of 45 months, nine patients are alive and disease-free following pro tocol chemotherapy. One patient with embryonal cancer developed progre ssive pulmonary metastases 3 months after completing high-dose therapy , underwent complete resection of lung metastases, and remains disease -free at 63+ months. Eight patients are continuously disease free at 2 3+ to 70+ months after protocol therapy. Eleven patients died of progr essive disease between 4 and 23 months following completion of treatme nt. Conclusion: These results compare favorably to other studies in si milarly selected patients undergoing salvage therapy with one or two c ycles of chemotherapy containing high-dose carboplatin and etoposide w ith or without cyclophosphamide (CTX) or IFX. The excellent safety and tolerability profile of this regimen and its encouraging activity in poor-prognosis patients make it worthy of further study as part of ini tial therapy in randomized protocols for high-risk disease and early i n the treatment of relapsed germ cell cancer. (C) 1996 by American Soc iety of Clinical Oncology.