Ifosfamide, paclitaxel, and cisplatin for patients with advanced transitional cell carcinoma of the urothelial tract: final report of a phase II trial evaluating two dosing schedules.
BACKGROUND
A combination regimen of ifosfamide, paclitaxel, and cisplatin (ITP), recycled every 4 weeks, was reported in the treatment of previously untreated patients with advanced transitional cell carcinoma (TCC). This study sought to examine ITP at 3-week intervals to assess its feasibility and toxicity, compare the results for different schedules, and assess the impact of prognostic factors and postchemotherapy surgery on outcome.


METHODS
ITP (ifosfamide 1.5 g/m(2) daily for 3 days, paclitaxel 200 mg/m(2) over 3 hours, and cisplatin 70 mg/m(2) on Day 1) was administered to patients with metastatic or unresectable TCC and was recycled every 4 weeks (for 30 patients) or 3 weeks (for 15 patients). Granulocyte-colony stimulating factor was given during each cycle.


RESULTS
Thirty of 44 assessable patients (68%; 95% confidence interval, 52-81%) demonstrated a major response (10 complete responses [23%], 20 partial [45%]), with durations of response ranging from 4 to 36 months. At a median follow-up of 28 months, the median survival was 20 months. Eleven patients (25%) were disease free at last follow-up. Overall toxicity for the 15 patients whose treatment was recycled at 3 weeks was similar to that for patients treated every 4 weeks. Hematologic toxicity included anemia, thrombocytopenia, and febrile neutropenia. Febrile neutropenia was observed in 7 patients (16%) and in 3.3% of cycles of therapy. No Grade 4 nonhematologic toxicity was observed. Grade 3 nonhematologic toxicity included alopecia, renal insufficiency (11%), and neuropathy (9%).


CONCLUSIONS
ITP is an active, well-tolerated regimen for previously untreated patients with TCC of the urothelial tract, resulting in a median survival of 20 months. Treatment can be recycled at 3-week intervals without enhanced toxicity.
Bajorin
D F
DF
Genitourinary Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
McCaffrey
J A
JA
Dodd
P M
PM
Hilton
S
S
Mazumdar
M
M
Kelly
W K
WK
Herr
H
H
Scher
H I
HI
Icasiano
E
E
Higgins
G
G
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D015331:Cohort Studies; D018572:Disease-Free Survival; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D043823:Taxoids; D013997:Time Factors; D014571:Urologic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery
D043823:Taxoids; D017239:Paclitaxel; D002945:Cisplatin; D007069:Ifosfamide