title: A phase I/II study of a stepwise dose-escalated regimen of cisplatin, etoposide and ifosfamide plus granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with advanced germ cell tumours.
abstract: In order to improve the survival of patients with metastatic advanced disease germ cell tumours (according to Indiana University classification), 77 patients were treated by a stepwise dose-escalated combination regimen of platinum (P), etoposide (E) and ifosfamide (I) (PEI) followed by application of granulocyte-macrophage colony-stimulating factor (GM-CSF) (10 micrograms/kg subcutaneously per day at levels 2 and 3) starting the first day after chemotherapy for 10 consecutive days. The maximally tolerated dose was reached at the third dose level with P 30 mg/m2, E 200 mg/m2 and I 1.6 g/m2, all given for 5 days, once every 21 days, for a total of four cycles. Sixty-seven per cent of patients had three or more metastatic sites. Twenty-two per cent of patients had extragonadal primary tumours. 49 (65%) patients achieved complete remission, and 9 additional patients (12%) achieved marker normalisation with unresectable residual disease. After a median follow-up of 27 months, the overall survival is 80%, with 67% of patients remaining free from progression. The dose-limiting toxicities were WHO grades 3/4 mucositis/enteritis in 33% of patients and prolonged thrombocytopenia < 20.000/microliters (> 10 days). Adverse reactions to GM-CSF occurred in 13% of patients. The use of a single haematopoietic growth factor allowed only a moderate increase in dose intensity (factor 1.37). Peripheral blood stem cells will be additionally incorporated into the treatment protocol in order to deliver multiple cycles of an upfront dose-intensified PEI regimen in patients with "poor risk" germ cell tumours with less toxicity.
authors.affiliation: Department of Hematology/Oncology, Hannover University Medical School, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Bokemeyer
authors.forename: H J
authors.initials: HJ
authors.lastname: Schmoll
authors.forename: A
authors.initials: A
authors.lastname: Harstrick
authors.forename: H J
authors.initials: HJ
authors.lastname: Illiger
authors.forename: B
authors.initials: B
authors.lastname: Metzner
authors.forename: U
authors.initials: U
authors.lastname: Räth
authors.forename: J
authors.initials: J
authors.lastname: Hohnloser
authors.forename: C
authors.initials: C
authors.lastname: Clemm
authors.forename: W
authors.initials: W
authors.lastname: Berdel
authors.forename: W
authors.initials: W
authors.lastname: Siegert
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D018237:Germinoma / Q000188:drug therapy*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D008297:Male; D009362:Neoplasm Metastasis; D013736:Testicular Neoplasms / Q000188:drug therapy*; D013921:Thrombocytopenia / Q000139:chemically induced; D016896:Treatment Outcome
chemical_list: D005047:Etoposide; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D002945:Cisplatin; D007069:Ifosfamide