Comparison of two standard chemotherapy regimens for good-prognosis germ cell tumors: updated analysis of a randomized trial.
BACKGROUND
The Australian and New Zealand Germ Cell Trials Group conducted a multicenter randomized phase III trial in men with good-prognosis germ cell tumors of two standard chemotherapy regimens that contained bleomycin, etoposide, and cisplatin but differed in the scheduling and total dose of cisplatin, the total dose of bleomycin, and the scheduling and dose intensity of etoposide. The trial was stopped early at a median follow-up of 33 months after a planned interim analysis found a survival benefit for the more dose-intense regimen. The aim of this analysis was to determine if this survival benefit was maintained with long-term follow-up.


METHODS
Between February 1994 and April 2000, 166 men with good-prognosis metastatic germ cell tumors defined by modified Memorial Sloan-Kettering criteria were randomly assigned to receive 3B(90)E(500)P (three cycles, repeated every 21 days, of 30 kU bleomycin on days 1, 8, and 15; 100 mg/m(2) etoposide on days 1-5; and 20 mg/m(2) cisplatin on days 1-5; n = 83) or 4B(30)E(360)P (four cycles, repeated every 21 days, of 30 kU bleomycin on day 1, 120 mg/m(2) etoposide on days 1-3, and 100 mg/m(2) cisplatin on day 1; n = 83). Endpoints included overall survival, progression-free survival, and quality of life and side effects, which were assessed using the Spitzer Quality of Life Index and the GLQ-8, respectively, before random assignment and during and after treatment. All analyses were by intention to treat. All P values are two-sided.


RESULTS
The median follow-up was 8.5 years. All but five survivors (3%) were followed up for at least 5 years. Overall survival remained better in those assigned to 3B(90)E(500)P than in those assigned to 4B(30)E(360)P (8-year survival: 92% vs 83%; hazard ratio of death = 0.38, 95% confidence interval = 0.15 to 0.97, P = .037). Progression-free survival favored 3B(90)E(500)P but was not statistically significantly different between the treatment groups (8-year progression-free survival, 3B(90)E(500)P vs 4B(30)E(360)P: 86% vs 79%; hazard ratio of progression = 0.6, 95% confidence interval = 0.3 to 1.1, P = .15). At the end of treatment, average scores for most side effect scales favored 3B(90)E(500)P. After the completion of treatment, average GLQ-8 scores for numbness (P = .003) and hair loss (P = .04) and the Spitzer Quality of Life Index (P = .05) favored 3B(90)E(500)P.


CONCLUSIONS
The survival benefit of 3B(90)E(500)P over 4B(30)E(360)P was maintained with long-term follow-up.
Grimison
Peter S
PS
Sydney Cancer Centre, Gloucester House 6, Royal Prince Alfred Hospital, Missenden Rd, Camperdown, NSW 2050, Australia. peter.grimison@ctc.usyd.edu.au
Stockler
Martin R
MR
Thomson
Damien B
DB
Olver
Ian N
IN
Harvey
Vernon J
VJ
Gebski
Val J
VJ
Lewis
Craig R
CR
Levi
John A
JA
Boyer
Michael J
MJ
Gurney
Howard
H
Craft
Paul
P
Boland
Amy L
AL
Simes
R John
RJ
Toner
Guy C
GC
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001315:Australia; D001761:Bleomycin / Q000008:administration & dosage; D002945:Cisplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005047:Etoposide / Q000008:administration & dosage; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009373:Neoplasms, Germ Cell and Embryonal / Q000188:drug therapy* / Q000556:secondary; D009520:New Zealand; D011379:Prognosis; D011788:Quality of Life; D018239:Seminoma / Q000188:drug therapy; D013736:Testicular Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016896:Treatment Outcome; D055815:Young Adult
D001761:Bleomycin; D005047:Etoposide; D002945:Cisplatin