Antitumoral activity of oxaliplatin/cisplatin-based combination therapy in cisplatin-refractory germ cell cancer patients.
OBJECTIVE
Only 20-30% of patient with advanced germ cell tumors, relapsing after standard first-line therapy, are curable with current second-line cisplatin-based regimens. New salvage combinations incorporating new active agents are needed. We report the toxicity/tolerance of a new salvage regimen based on the oxaliplatin (Eloxatin)/cisplatin combination, evaluated in patients with recurrent, mostly cisplatin-refractory germ cell tumors.


METHODS
Thirteen patients were enrolled in this study. All except one had received cisplatin-based chemotherapy. Eight had progressive disease as the best response on their last platinum-based chemotherapy, and three had potentially sensitive tumors. The median interval since the last platinum-based chemotherapy was 6 months (range: 1-36 months). One untreated patient with poor prognosis was also enrolled. Twelve patients had pathological markers [median alpha-fetoprotein 14 800 ng/ml (58-10(6)), median human chorionic gonadotrophin beta subunit 7000 IU/ml (37-723 700)]. Patients received either oxaliplatin (130 mg/m(2)) and cisplatin (100 mg/m(2)) every 3-4 weeks (Bi regimen, four patients), or the same regimen combined with one to four of the following cytotoxic agents: ifosfamide, epirubicin, vinorelbine, methotrexate, dactinomycin, etoposide and bleomycin (BiC regimen, 9 patients). Treatment was individualized according to each individual patient's pretreatment and clinical characteristics.


RESULTS
Seven objective responses were obtained (overall response rate = 54%), all with the BiC regimens (two complete and five partial responses). Two patients with recurrent disease achieved a long-term complete response lasting over 5 years. Four partial responders were seen in the eight cisplatin-refractory tumors, lasting 4-8 months. All objective responses had a corroborating major decrease in tumor marker blood levels (median decrease: 99.7%). The median survival for the whole group was 8 months. The commonest severe toxicity was hematological (grade 4 neutropenia in 78% and thrombopenia in 74% of the BiC cycles).


CONCLUSIONS
Our combined salvage regimen induced significant antitumoral activity in recurrent, cisplatin-refractory germ cell tumors. Oxaliplatin merits further evaluation as a component of combination therapy for this disease.
Soulié
P
P
FSMSIT, Hôpital Paul Brousse, 12-14, Avenue Paul Vaillant-Couturier, F-94800 Villejuif, France.
Garrino
C
C
Bensmaïne
M A
MA
Bekradda
M
M
Brain
E
E
Di Palma
M
M
Goupil
A
A
Misset
J L
JL
Cvitkovic
E
E
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001761:Bleomycin / Q000627:therapeutic use; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000097:blood / Q000187:drug effects; D002945:Cisplatin / Q000627:therapeutic use*; D003609:Dactinomycin / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D004359:Drug Therapy, Combination; D015251:Epirubicin / Q000627:therapeutic use; D005047:Etoposide / Q000627:therapeutic use; D018237:Germinoma / Q000188:drug therapy*; D006801:Humans; D007069:Ifosfamide / Q000627:therapeutic use; D008297:Male; D009364:Neoplasm Recurrence, Local; D009503:Neutropenia / Q000139:chemically induced; D009944:Organoplatinum Compounds / Q000627:therapeutic use*; D000077150:Oxaliplatin; D016879:Salvage Therapy; D013736:Testicular Neoplasms / Q000188:drug therapy*; D013921:Thrombocytopenia / Q000139:chemically induced; D016896:Treatment Outcome; D014747:Vinblastine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000077235:Vinorelbine; D000509:alpha-Fetoproteins / Q000187:drug effects / Q000378:metabolism
D018997:Chorionic Gonadotropin, beta Subunit, Human; D009944:Organoplatinum Compounds; D000509:alpha-Fetoproteins; D000077150:Oxaliplatin; D001761:Bleomycin; D003609:Dactinomycin; D015251:Epirubicin; D014747:Vinblastine; D005047:Etoposide; D002945:Cisplatin; D000077235:Vinorelbine; D007069:Ifosfamide