Treatment options for muscle-invasive urothelial cancer for patients who were not eligible for cystectomy or neoadjuvant chemotherapy with methotrexate, vinblastine, doxorubicin, and cisplatin: report of Southwest Oncology Group Trial 8733.
BACKGROUND
Many patients with invasive urothelial cell cancer are poor candidates for cisplatin-based chemotherapy, and many are high risk for cystectomy. Southwest Oncology Group Trial 8733 was designed to address treatment for such patients.


METHODS
Eligible patients had primary or recurrent muscle-invasive disease with transitional cell or squamous cell histology, a performance status from 0 to 2, no extrapelvic disease, a life expectancy >3 months, and adequate hematologic function. The treating clinician assigned patients to operable or inoperable groups. All patients received 2 cycles of 5-fluorouracil (5-FU) at a dose of 1000 mg/m(2) per day x 4 starting concurrently with radiation at a dose of 200 centigrays per day x 10 each cycle. After 2 cycles, operable patients with positive biopsies underwent cystectomy, and patients with negative biopsies received a third cycle of chemoradiotherapy. Patients in the inoperable group received 3 cycles without interim biopsy.


RESULTS
Eighteen of 24 eligible patients in the operable group were evaluable for response. Five patients had a complete response (CR), 9 patients had stable disease, 1 patient had progressive disease, and 3 patients were not assessable. The median progression-free survival was 10 months (95% confidence interval [95% CI], 4-14 months), and the median overall survival was 18 months (95% CI, 7-28 months). In the inoperable group, 35 of 37 eligible patients were evaluable for response with 17 CRs (49%; 95% CI, 31%-66%). The median progression-free survival was 13 months (95% CI, 10-17 months), and the median overall survival was 20 months (95% CI, 11-53 months). There were no episodes of grade 4 toxicity.


CONCLUSIONS
In the current study, the combination of 5-FU and radiation was found to be tolerated well by patients with numerous comorbidities who could not tolerate cisplatin-based therapy or cystectomy.
Higano
Celestia S
CS
Department of Medicine, Division of Oncology, University of Washington, Seattle, Washington, USA.
Tangen
Catherine M
CM
Sakr
Wael A
WA
Faulkner
James
J
Rivkin
Saul E
SE
Meyers
Frederick J
FJ
Hussain
Maha
M
Baker
Laurence H
LH
Russell
Kenneth J
KJ
Crawford
E David
ED
D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D015653:Cystectomy; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D019042:Muscle Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*; D020360:Neoadjuvant Therapy; D011379:Prognosis; D015996:Survival Rate; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*; D014747:Vinblastine / Q000008:administration & dosage
D014747:Vinblastine; D004317:Doxorubicin; D002945:Cisplatin; D005472:Fluorouracil; D008727:Methotrexate