Randomized trial comparing bleomycin/etoposide/cisplatin with alternating cisplatin/cyclophosphamide/doxorubicin and vinblastine/bleomycin regimens of chemotherapy for patients with intermediate- and poor-risk metastatic nonseminomatous germ cell tumors: Genito-Urinary Group of the French Federation of Cancer Centers Trial T93MP.
OBJECTIVE
Two chemotherapy regimens for intermediate- and poor-risk metastatic nonseminomatous germ cell tumors were compared for efficacy and toxicity.


METHODS
From February 1994 to February 2000, 190 patients were randomly assigned between either four cycles of BEP (bleomycin 30 mg d1, d8, d15; etoposide 100 mg/m(2) d1-5; cisplatin 20 mg/m(2) d1-5) or four to six alternating cycles of CISCA/VB (cyclophosphamide 400 mg/m(2) d1-2, doxorubicin 35 mg/m(2) d1-2, cisplatin 100 mg/m(2) d3/vinblastine 2.5 mg/m(2) d1-5, bleomycin 25 mg/m(2) d1-5). Risk was initially defined according to the Institut Gustave Roussy (Villejuif, France) prognostic model based on serum alpha-fetoprotein and human chorionic gonadotropin levels only. Patients were retrospectively assigned into the International Germ Cell Consensus Classification.


RESULTS
Among 185 assessable patients, favorable responses did not differ statistically between the two arms: 49 in the CISCA/VB arm (56%; 95% CI, 45% to 66%), 57 in the BEP arm (65%; 95% CI, 55% to 75%). The CISCA/VB regimen induced more significant hematologic and mucous toxicities compared with the BEP arm. The 5-year event-free survival rates were 37% (95% CI, 27% to 47%) and 47% (95% CI, 37% to 57%) in CISCA/VB and BEP arms, respectively (hazard ratio [HR] = 0.76; 95% CI, 0.52 to 1.11; P = .15). With a median follow-up of 7.8 years, the 5-year overall survival rates were 59% (95% CI, 47% to 67%) and 69% (95% CI, 58% to 77%) in CISCA/VB and BEP arms, respectively (HR = 0.73; 95% CI, 0.46 to 1.18; P = .24).


CONCLUSIONS
Because of equivalent efficacy and lesser toxicity, the standard treatment for patients with intermediate- and poor-risk metastatic nonseminomatous germ cell tumors remains four cycles of BEP.
Culine
Stéphane
S
Centre Regional de Lutte contre le Cancer Val d'Aurelle, Montpellier, France. stculine@valdorel.fnclcc.fr
Kramar
Andrew
A
Théodore
Christine
C
Geoffrois
Lionel
L
Chevreau
Christine
C
Biron
Pierre
P
Nguyen
Binh Bui
BB
Héron
Jean-François
JF
Kerbrat
Pierre
P
Caty
Armelle
A
Delva
Rémy
R
Fargeot
Pierre
P
Fizazi
Karim
K
Bouzy
Jeannine
J
Droz
Jean-Pierre
JP
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001761:Bleomycin / Q000627:therapeutic use; D002945:Cisplatin / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000627:therapeutic use; D004317:Doxorubicin / Q000627:therapeutic use; D005047:Etoposide / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008479:Mediastinal Neoplasms / Q000188:drug therapy*; D008875:Middle Aged; D009373:Neoplasms, Germ Cell and Embryonal / Q000188:drug therapy*; D011379:Prognosis; D012186:Retroperitoneal Neoplasms / Q000188:drug therapy*; D015996:Survival Rate; D013736:Testicular Neoplasms / Q000188:drug therapy*; D016896:Treatment Outcome; D014747:Vinblastine / Q000627:therapeutic use
D001761:Bleomycin; D014747:Vinblastine; D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide; D002945:Cisplatin