Salvage treatment with paclitaxel, ifosfamide, and cisplatin plus high-dose carboplatin, etoposide, and thiotepa followed by autologous stem-cell rescue in patients with relapsed or refractory germ cell cancer.
OBJECTIVE
To study feasibility and efficacy of a new salvage regimen in patients with relapsed and/or refractory germ cell tumors.


METHODS
Between May 1995 and February 1997, 80 patients were entered onto a phase II study. Conventional-dose salvage treatment with three cycles of paclitaxel 175 mg/m(2), ifosfamide 5 x 1.2 g/m(2), and cisplatin 5 x 20 mg/m(2) (TIP) was followed by one cycle of high-dose chemotherapy (HDCT) with carboplatin 500 mg/m(2) x 3, etoposide 600 mg/m(2) x 4, and thiotepa 150 to 250 mg/m(2) x 3 (CET). In 23 patients, one additional cycle of paclitaxel 175 mg/m(2) and ifosfamide 5 g/m(2) (TI) was given immediately before TIP to improve stem-cell mobilization.


RESULTS
Fifty-five (69%) of 80 patients responded to TIP, 24 (30%) of 80 patients had stable disease (n = 5) or tumor progression (n = 19), and one patient died. Only 62 (78%) of 80 patients received subsequent HDCT. Among those, 41 (66%) of 62 patients responded and 20 (32%) of 62 patients had stable disease (n = 3) or tumor progression (n = 17). One patient died after HDCT from multiorgan failure. Survival probabilities at 3 years were 30% for overall and 25% for event-free survival. Peripheral neurotoxicity with sensorimotor impairment grade 2 through 4 in 29%, paresthesias grade 2 through 4 in 24%, and skin toxicity grade 2 through 3 in 15% of patients were the most relevant side effects.


CONCLUSIONS
Treatment with TIP followed by high-dose CET is feasible and can induce long-term remissions in 25% of patients with relapsed or refractory germ cell tumors. Peripheral nervous toxicity in approximately one third of patients is a disadvantage of this salvage strategy.
Rick
O
O
Department of Hematology, Charité, Campus Virchow Klinikum, Berlin, Germany.
Bokemeyer
C
C
Beyer
J
J
Hartmann
J T
JT
Schwella
N
N
Kingreen
D
D
Neureither
S
S
Metzner
B
B
Casper
J
J
Wandt
H
H
Hartmann
F
F
Schmoll
H J
HJ
Derigs
G
G
Gerl
A
A
Berdel
W E
WE
Kanz
L
L
Siegert
W
W
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005858:Germany / Q000453:epidemiology; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D008297:Male; D008479:Mediastinal Neoplasms / Q000628:therapy; D009373:Neoplasms, Germ Cell and Embryonal / Q000401:mortality / Q000628:therapy*; D017239:Paclitaxel / Q000008:administration & dosage; D016879:Salvage Therapy / Q000379:methods*; D015996:Survival Rate; D013736:Testicular Neoplasms / Q000628:therapy; D013852:Thiotepa / Q000008:administration & dosage
D013852:Thiotepa; D017239:Paclitaxel; D002945:Cisplatin; D007069:Ifosfamide