title: Alternating dose-dense chemotherapy in patients with high volume disseminated non-seminomatous germ cell tumours.
abstract: Only about half of patients with a poor-prognosis non-seminomatous germ-cell tumours can achieve a cure. The aim of this phase II study was to assess the efficacy and toxicity of a dose-dense alternating chemotherapy regimen in this subset of patients. High volume non-seminomatous germ-cell tumours was defined as follows: at least two sites of non pulmonary metastases, an extragonadal primary tumour, a serum human chorionic gonadotropin level higher than 10 000 mIU x ml(-1), or a alpha-foetoprotein level higher than 2000 mIU ml(-1). Patients who fulfilled these criteria were treated with the so-called BOP-CISCA-POMB-ACE regimen (bleomycin, vincristine, and cisplatin; cisplatin, cyclophosphamide, and doxorubicin; cisplatin, vincristine, methotrexate, and bleomycin; etoposide, dactinomycin, and cyclophosphamide) plus granulocyte colony-stimulating factor. A total of 58 patients were enrolled. Patients were retrospectively classified according to the International Germ-Cell Cancer Consensus Group classification; 38 patients (66%) had poor-prognosis disease and 19 patients (33%) had intermediate-prognosis. Patients received a median of 2.5 courses (range 0.25 to five courses) of the BOP-CISCA-POMB-ACE regimen. Forty-two patients (72.4%) had a complete response to therapy. With a median follow-up time of 31 months, the 3-year progression-free survival rate was 71% (95% confidence interval, 60 to 84%) and the 3-year overall survival rate was 73% (95% confidence interval: 62 to 86%). The 3-year PFS rates were 83% (95% confidence interval: 68 to 100%) in the intermediate-prognosis group and 65% (95% confidence interval: 51 to 82%) in the poor-prognosis group. Early side effects included mainly grade 4 haematologic toxicity (neutropaenia in 79% of patients, thrombocytopaenia in 69%, anaemia in 22%), grade 4 stomatitis (19%), and four early deaths (7% of patients), at least partially related to toxicity. The dose-dense BOP-CISCA-POMB-ACE regimen is highly active in patients with non-seminomatous germ-cell tumours classified as intermediate-prognosis or poor-prognosis according to the International Germ-Cell Cancer Consensus Group. Because outcomes with this regimen compare favourably with outcome after standard therapy, dose-dense chemotherapy should be further investigated in this subset of patients.
authors.affiliation: Department of Genitourinary Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA. fizazi@igr.fr
authors.forename: K
authors.initials: K
authors.lastname: Fizazi
authors.forename: D M
authors.initials: DM
authors.lastname: Prow
authors.forename: K-A
authors.initials: KA
authors.lastname: Do
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.forename: L
authors.initials: L
authors.lastname: Finn
authors.forename: J
authors.initials: J
authors.lastname: Kim
authors.forename: D
authors.initials: D
authors.lastname: Daliani
authors.forename: C N
authors.initials: CN
authors.lastname: Papandreou
authors.forename: S-M
authors.initials: SM
authors.lastname: Tu
authors.forename: R E
authors.initials: RE
authors.lastname: Millikan
authors.forename: L C
authors.initials: LC
authors.lastname: Pagliaro
authors.forename: C J
authors.initials: CJ
authors.lastname: Logothetis
authors.forename: R J
authors.initials: RJ
authors.lastname: Amato
mesh_terms: D000293:Adolescent; D000328:Adult; D000754:Anemia, Refractory, with Excess of Blasts / Q000139:chemically induced; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood; D001761:Bleomycin / Q000008:administration & dosage / Q000009:adverse effects; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D003609:Dactinomycin / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D018237:Germinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000556:secondary; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000556:secondary; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced; D011379:Prognosis; D011446:Prospective Studies; D012074:Remission Induction; D018239:Seminoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000556:secondary; D016019:Survival Analysis; D015996:Survival Rate; D013736:Testicular Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D014408:Biomarkers, Tumor; D001761:Bleomycin; D003609:Dactinomycin; D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide; D002945:Cisplatin; D008727:Methotrexate