Sequential high-dose chemotherapy protocol for relapsed poor prognosis germ cell tumors combining two mobilization and cytoreductive treatments followed by three high-dose chemotherapy regimens supported by autologous stem cell transplantation. Results of the phase II multicentric TAXIF trial.
BACKGROUND
High-dose chemotherapy (HD-CT) is able to circumvent platinum resistance of resistant/refractory germ-cell tumors (GCTs), but expectancy of cure remains low. New strategies are needed with new drugs and a sequential approach.


METHODS
Patients with relapsed poor-prognosis GCTs were scheduled to receive two cycles combining epirubicin and paclitaxel (Taxol) followed by three consecutive HD-CT supported by stem cell transplantation [one course combining cyclophosphamide, 3 g/m(2) + thiotepa, 400 mg/m(2), followed by two ICE regimens (ifosfamide, 10 g/m(2), carboplatin, AUC 20, etoposide, 1500 mg/m(2))].


RESULTS
From March 1998 to September 2001 (median follow-up, 31.8 months), 45 patients (median age, 28 years) were enrolled in this phase II study. Twenty-two patients received the complete course. Twenty-five patients died from progression and five from toxicity. The overall response rate was 37.7%, including an 8.9% complete response rate. The median overall survival was 11.8 months. The 3-year survival and progression-free survival rate was 23.5%. The 'Beyer' prognostic score predicted the outcome after HD-CT.


CONCLUSIONS
Although our results warrant further studies on HD-CT in relapsed poor prognosis GCTs, patients with a Beyer score >2 did not benefit from this approach and should not be enrolled in HD-CT trials. Better selection criteria have to be fulfilled in forthcoming studies.
Lotz
J-P
JP
Department of Medical Oncology, Hôpital Tenon, Paris, France. jean-pierre.lotz@tnn.ap-hop-paris.fr
Bui
B
B
Gomez
F
F
Théodore
C
C
Caty
A
A
Fizazi
K
K
Gravis
G
G
Delva
R
R
Peny
J
J
Viens
P
P
Duclos
B
B
De Revel
T
T
Curé
H
H
Gligorov
J
J
Guillemaut
S
S
Ségura
C
C
Provent
S
S
Droz
J-P
JP
Culine
S
S
Biron
P
P
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D015251:Epirubicin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D009373:Neoplasms, Germ Cell and Embryonal / Q000188:drug therapy* / Q000473:pathology*; D017239:Paclitaxel / Q000008:administration & dosage; D011379:Prognosis; D033581:Stem Cell Transplantation; D013736:Testicular Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D014182:Transplantation, Autologous; D016896:Treatment Outcome
D015251:Epirubicin; D005047:Etoposide; D016190:Carboplatin; D017239:Paclitaxel; D007069:Ifosfamide