A Systemic Hyperthermia Oncologic Working Group trial. Ifosfamide, carboplatin, and etoposide combined with 41.8 degrees C whole-body hyperthermia for metastatic soft tissue sarcoma.
BACKGROUND
Based on earlier clinical and preclinical studies, we conducted a phase II trial in metastatic sarcoma patients of the combination of 41.8 degrees C (x60 min) radiant heat (Aquatherm) whole-body hyperthermia (WBH) with 'ICE' chemotherapy. The ICE regimen consists of ifosfamide (5 g/m(2)), carboplatin (300 mg/m(2)) and etoposide (100 mg/m(2)), concurrent with WBH, with etoposide also on days 2 and 3 post-WBH.


METHODS
Therapy was delivered every 4 weeks for a maximum of 4 cycles. All patients received filgrastim or lenograstim.


RESULTS
Of 108 patients enrolled as of September 2001, 95 are evaluable for response. Of the evaluable patients (mean ECOG performance status approximately 1; mean age 42.3; 58% male) 33 had no prior therapy for metastatic disease, and 62 were pretreated (mean: 1.5 prior regimens). The overall response rate was 28.4% (4 complete remissions and 23 partial remissions) with stable disease (SD) in 31 patients. For no prior therapy, the response rate was 36%; in pretreated patients it was 24%. The median overall survival by Kaplan-Meier estimates was 393 days (95% CI 327, 496); the median time to treatment failure was 123 days (95% CI 77, 164). The major toxicity (287 cycles) was grade 3 or 4 neutropenia and thrombocytopenia seen in 79.7 and 60.6% of treatments respectively; there were 7 episodes of infection (grade 3/4) with 2 treatment-related deaths, bot involving disease progression and ureteral obstruction.


CONCLUSIONS
These results are consistent with continued clinical investigation of this combined modality approach.
Westermann
A M
AM
Academic Medical Center, Amsterdam, The Netherlands.
Wiedemann
G J
GJ
Jager
E
E
Jager
D
D
Katschinski
D M
DM
Knuth
A
A
Vörde Sive Vörding
P Z
PZ
Van Dijk
J D P
JD
Finet
J
J
Neumann
A
A
Longo
W
W
Bakhshandeh
A
A
Tiggelaar
C L
CL
Gillis
W
W
Bailey
H
H
Peters
S O
SO
Robins
H I
HI
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D006801:Humans; D006979:Hyperthermia, Induced; D007069:Ifosfamide / Q000008:administration & dosage; D000078224:Lenograstim; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000627:therapeutic use; D012509:Sarcoma / Q000188:drug therapy / Q000628:therapy*; D016019:Survival Analysis; D016896:Treatment Outcome
D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D005047:Etoposide; D000078224:Lenograstim; D016190:Carboplatin; D000069585:Filgrastim; D007069:Ifosfamide