A randomized phase III study comparing standard dose BEP with sequential high-dose cisplatin, etoposide, and ifosfamide (VIP) plus stem-cell support in males with poor-prognosis germ-cell cancer. An intergroup study of EORTC, GTCSG, and Grupo Germinal (EORTC 30974).
BACKGROUND
To compare the efficacy of one cycle of standard dose cisplatin, etoposide, and ifosfamide (VIP) plus three cycles of high-dose VIP followed by stem-cell infusion [high-dose chemotherapy (HD-CT arm)] to four cycles of standard cisplatin, etoposide, and bleomycin (BEP) in patients with poor-prognosis germ-cell cancer (GCC).


METHODS
Patients with poor-prognosis GCC were assigned to receive either BEP or VIP followed by HD-CT. To show a 15% improvement in a 1-year failure-free survival (FFS), the study aimed to recruit 222 patients but closed with 137, due to slow accrual.


RESULTS
One hundred thirty-one patients were included in this analysis. The complete response rates in the HD-CT and in the BEP arm did not differ: (intention to treat) 44.6% versus 33.3% (P = 0.18). There was no difference in FFS between the two treatment arms (P = 0.057, 66 events). At 2 years, the FFS rate was 44.8% [95% confidence interval (CI) 32.5-56.4] and 58.2%, respectively (95% CI 48.0-71.9); but this 16.3% (standard deviation 7.5%) difference was not statistically significant (P = 0.060). Overall survival did not differ between the two groups (log-rank P > 0.1, 47 deaths).


CONCLUSIONS
This study could not demonstrate that high-dose chemotherapy given as part of first-line therapy improves outcome in patients with poor-prognosis GCC.
Department of Oncology, Rigshospitalet, Copenhagen, Denmark. Electronic address: gedske.daugaard@rh.regionh.dk.
G
G
Daugaard
Department of Urology, Chemotherapy Unit, Maria Sklodowska-Curie Memorial Center, Warsaw, Poland.
I
I
Skoneczna
Department of Oncology, Oslo University Hospital and University of Oslo, Oslo, Norway.
N
N
Aass
Department Medical Oncology, Erasmus University Hospital, Rotterdam, The Netherlands.
R
R
De Wit
LBI-ACR VIEnna and ACR-ITR VIEnna/CEADDP-Kaiser Franz Josef-Spital, Vienna, Austria.
M
M
De Santis
Department of Oncology, University Hospitals, Leuven, Belgium.
H
H
Dumez
European Organization for Research and Treatment of Cancer Headquarters, Brussels, Belgium.
S
S
Marreaud
European Organization for Research and Treatment of Cancer Headquarters, Brussels, Belgium.
L
L
Collette
Institut Català d'Oncologia, Htal. Duran i Reynals, Hòspitalet Barcelona, Barcelona, Spain.
J R G
JRG
Lluch
Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald Cancer Center (UCCH), University Medical Center Hamburg Eppendorf, Hamburg.
C
C
Bokemeyer
Department of Oncology and Hematology, Martin Luther University, Halle, Germany.
H J
HJ
Schmoll
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood*; D001761:Bleomycin / Q000009:adverse effects / Q000627:therapeutic use; D006063:Chorionic Gonadotropin / Q000097:blood; D002945:Cisplatin / Q000009:adverse effects / Q000627:therapeutic use; D018572:Disease-Free Survival; D005047:Etoposide / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D007069:Ifosfamide / Q000009:adverse effects / Q000627:therapeutic use; D053208:Kaplan-Meier Estimate; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D008479:Mediastinal Neoplasms / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009373:Neoplasms, Germ Cell and Embryonal / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D011379:Prognosis; D012186:Retroperitoneal Neoplasms / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D033581:Stem Cell Transplantation; D013736:Testicular Neoplasms / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D055815:Young Adult; D000509:alpha-Fetoproteins / Q000378:metabolism
C097353:AFP protein, human; D014408:Biomarkers, Tumor; D006063:Chorionic Gonadotropin; D000509:alpha-Fetoproteins; D001761:Bleomycin; D005047:Etoposide; D007770:L-Lactate Dehydrogenase; D002945:Cisplatin; D007069:Ifosfamide