A Phase II study of paclitaxel and ifosfamide for patients with advanced refractory carcinoma of the urothelium.
BACKGROUND
Cisplatin-based combination chemotherapy for patients with advanced transitional cell carcinoma (TCC) of the urothelium has limitations, and new therapies need to be evaluated.


METHODS
Ifosfamide 1.0 gm/m2 on Days 1-4 and paclitaxel 135 mg/m2 by 24-hour infusion on Day 4 were administered to 26 patients with locally unresectable or metastatic TCC. Cycles were repeated every 21 days for a maximum of 6 cycles; dose escalation was dependent on whether Grade 3 or 4 toxicities occurred.


RESULTS
There were 24 males and 2 females, with a median age of 66 years and a median Eastern Cooperative Oncology Group performance status of 0. The median number of cycles administered was 3. Twelve patients had Grade 3 or 4 hematologic toxicities, including 1 patient who died of a gastrointestinal hemorrhage while pancytopenic. There were no episodes of neutropenic fever. Two patients each had a complete response (CR) that lasted 5 and 28 months, respectively (response rate: 15%; 95% CI: 2-45%), among the 13 patients who had received prior chemotherapy. Of the 13 patients without prior chemotherapy, there were 3 with complete responses and 1 with a partial response ranging from 8 to 25+ months (RR: 30.7%; 95% CI: 9-61%).


CONCLUSIONS
The combination of ifosfamide and paclitaxel is well tolerated and can produce objective responses in patients who are chemonaïve or have had prior therapy. For previously untreated patients, the addition of ifosfamide does not appear to result in a better response rate than single agent paclitaxel; and for previously treated patients, the addition of paclitaxel does not appear to result in a better response rate than single agent ifosfamide.
Sweeney
C J
CJ
Department of Medicine, Indiana University Medical Center, Indianapolis, USA.
Williams
S D
SD
Finch
D E
DE
Bihrle
R
R
Foster
R S
RS
Collins
M
M
Fox
S
S
Roth
B J
BJ
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000473:pathology; D004334:Drug Administration Schedule; D004341:Drug Evaluation; 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; D016019:Survival Analysis; D014571:Urologic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D019459:Urothelium
D017239:Paclitaxel; D007069:Ifosfamide