title: Treatment of germ cell cancer with two cycles of high-dose ifosfamide, carboplatin, and etoposide with autologous stem-cell support.
abstract: OBJECTIVE
  To evaluate the activity of two cycles of high-dose ifosfamide, carboplatin, and etoposide (ICE) with autologous hematopoietic progenitor cell support (aHPCS) in patients with poor-prognosis, chemotherapeutically sensitive germ cell cancer.
  
  
  METHODS
  Twenty patients with germ cell tumor who had persistent disease or relapse from standard-risk or high-risk presentation were entered on this pilot study. The entry criteria included relapsed gonadal and extragonadal germ cell cancer unlikely to be cured by standard salvage therapy but without proven refractoriness to chemotherapy. Treatment consisted of two cycles of ICE chemotherapy with mesna uroprotection and aHPCS. On the first cycle, ifosfamide (IFX), 2 gm/m2; carboplatin, 400 mg/m2; 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 additional IFX, 2 g/m2 on day -3 and 1 g/ m2 on day -2. Mesna, 600 mg/m2 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 assessable for toxicity and current disease status. Two patients received only one cycle of therapy, one because of the development of active hepatitis C following cycle 1, and one because of renal insufficiency. No patient died as a result of protocol therapy, and no patient developed debilitating peripheral neuropathy, symptomatic hearing loss, or severe renal insufficiency requiring dialysis. The median time to recovery of > or = 500 neutrophils/microL and platelets > or = 50,000/microL was day +11 and day +15, respectively. The median maximum creatinine was 1.6 mg/dL on each treatment cycle, and there was no other significant organ toxicity. With a median follow-up of 45 months, nine patients are alive and disease-free following protocol chemotherapy. One patient with embryonal cancer developed progressive 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 23+ to 70+ months after protocol therapy. Eleven patients died of progressive disease between 4 and 23 months following completion of treatment.
  
  
  CONCLUSIONS
  These results compare favorably to other studies in similarly selected patients undergoing salvage therapy with one or two cycles of chemotherapy containing high-dose carboplatin and etoposide with 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 initial therapy in randomized protocols for high-risk disease and early in the treatment of relapsed germ cell cancer.
authors.affiliation: Department of Medical Oncology, City of Hope National Medical Center, Duarte, CA 91010-3000, USA. kmargolin@smtplink.coh.org
authors.forename: K
authors.initials: K
authors.lastname: Margolin
authors.forename: J H
authors.initials: JH
authors.lastname: Doroshow
authors.forename: C
authors.initials: C
authors.lastname: Ahn
authors.forename: V
authors.initials: V
authors.lastname: Hamasaki
authors.forename: L
authors.initials: L
authors.lastname: Leong
authors.forename: R
authors.initials: R
authors.lastname: Morgan
authors.forename: J
authors.initials: J
authors.lastname: Raschko
authors.forename: S
authors.initials: S
authors.lastname: Shibata
authors.forename: G
authors.initials: G
authors.lastname: Somlo
authors.forename: M
authors.initials: M
authors.lastname: Tetef
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D018237:Germinoma / Q000097:blood / Q000188:drug therapy* / Q000601:surgery; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D008297:Male; D008479:Mediastinal Neoplasms / Q000188:drug therapy; D015080:Mesna / Q000008:administration & dosage; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy; D010865:Pilot Projects; D012186:Retroperitoneal Neoplasms / Q000188:drug therapy; D013736:Testicular Neoplasms / Q000188:drug therapy
chemical_list: D005047:Etoposide; D016190:Carboplatin; D015080:Mesna; D007069:Ifosfamide