High-dose chemotherapy as primary treatment for poor-risk germ-cell tumors: the Memorial Sloan-Kettering experience (1988-1999).
Although the majority of patients with poor-risk germ-cell tumors (GCTs) will achieve a durable complete remission (CR) with standard first-line therapy, 20% to 30% of them will either relapse or fail to achieve an initial CR and eventually die. For this reason, the strategy of using high-dose (HD) chemotherapy with autologous stem-cell support has been investigated to improve the chances of cure attainable in the salvage setting, but at a cost of significant morbidity and mortality. Treatment using HD therapy in the first-line setting offers the promise of reducing morbidity and mortality while increasing efficacy. At Memorial Sloan-Kettering Cancer Center (MSKCC), trials were conducted to test this hypothesis. Patients at high risk of relapse following conventional therapy were identified, based on post-treatment serum marker concentrations that failed to appropriately decline by predicted half-life after several cycles of standard treatment. These patients received first-line HD treatment. Patients received a 2-drug HD regimen in one trial and an intensified 3-drug regimen in another, each with autologous bone marrow transplantation. These patients had improved overall and event-free survival rates (p = 0.001 and 0.003, respectively) compared with historical controls who underwent standard first-line treatment, with a lower incidence of treatment-related mortality than patients who received HD therapy in the salvage setting. Randomized trials are under way to prospectively verify these results.
Morris
M J
MJ
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
Bosl
G J
GJ
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001761:Bleomycin / Q000008:administration & dosage; D016026:Bone Marrow Transplantation; D002173:Cancer Care Facilities; D016190:Carboplatin / Q000008:administration & dosage; D002945:Cisplatin / Q000008:administration & dosage; D003520:Cyclophosphamide / Q000008:administration & dosage; D003609:Dactinomycin / Q000008:administration & dosage; D018572:Disease-Free Survival; D005047:Etoposide / Q000008:administration & dosage; D018237:Germinoma / Q000188:drug therapy* / Q000401:mortality / Q000628:therapy*; D006801:Humans; D008297:Male; D009519:New York City; D012189:Retrospective Studies; D016879:Salvage Therapy; D015996:Survival Rate; D013736:Testicular Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000628:therapy*; D014182:Transplantation, Autologous; D014747:Vinblastine / Q000008:administration & dosage
D001761:Bleomycin; D003609:Dactinomycin; D014747:Vinblastine; D005047:Etoposide; D003520:Cyclophosphamide; D016190:Carboplatin; D002945:Cisplatin