High dose chemotherapy with ifosfamide, carboplatin, and etoposide combined with autologous bone marrow transplantation for the treatment of poor-prognosis germ cell tumors and metastatic trophoblastic disease in adults.
BACKGROUND
A Phase I-II trial to assess the toxicity and efficacy of a tandem high dose chemotherapy combining ifosfamide, carboplatin, and etoposide in germ cell tumors and metastatic trophoblastic disease was performed.


METHODS
Thirty-nine patients, with a total of 22 testicular tumors, 9 extragonadal germ cell tumors, 3 ovarian germ cell tumors, and 5 cases of metastatic trophoblastic disease, received tandem high dose therapy combining ifosfamide (7500-12,500 mg/m2), carboplatin (875-1225 mg/m2), and etoposide (1000-1250 mg/m2), followed by bone marrow reinfusion. Among the 39 patients, 33 were refractory to cisplatin- or carboplatin-based regimen and the response of 37 could be evaluated; 69 cycles of this tandem high dose therapy were administered.


RESULTS
The overall response rate was 46%, including a complete response (CR) rate of 35%. Of 21 patients with testicular tumors who could be evaluated, 10 (47%) achieved a CR. No CRs were obtained in patients with refractory extragonadal germ cell tumors. Nine partial responders after the first cycle became complete responders after the second. Nine (23%) of the patients were long term survivors (> 18 months), 7 of them in continuous CR. Side effects primarily were renal toxicity and enterocolitis. Seven patients (18%) died of therapy-related be explored and the maximum tolerated doses of this three-drug regimen remain to be determined.


CONCLUSIONS
This tandem therapeutic regimen is able to overcome resistance to a platinum-based regimen in highly refractory germ cell tumors and gestational trophoblastic disease and to cure a number of patients.
Lotz
J P
JP
Department of Medical Oncology, Hospital St-Louis, Paris, France.
André
T
T
Donsimoni
R
R
Firmin
C
C
Bouleuc
C
C
Bonnak
H
H
Merad
Z
Z
Esteso
A
A
Gerota
J
J
Izrael
V
V
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D003131:Combined Modality Therapy; D004760:Enterocolitis / Q000139:chemically induced; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D018237:Germinoma / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage / Q000009:adverse effects; D007668:Kidney / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000401:mortality; D011247:Pregnancy; D011379:Prognosis; D012074:Remission Induction; D015996:Survival Rate; D013736:Testicular Neoplasms / Q000188:drug therapy* / Q000401:mortality; D014182:Transplantation, Autologous; D014328:Trophoblastic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D014594:Uterine Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology
D005047:Etoposide; D016190:Carboplatin; D007069:Ifosfamide