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.

On reversing the persistence of memory: hematopoietic stem cell transplant for autoimmune disease in the first ten years.

There has been a remarkable history in the treatment of patients with autoimmune disease in the last century. Prior to the development of newer NSAIDs and corticosteroids, the care of patients with autoimmune disease was limited to aspirin and generally homeopathic therapies such as paraffin. In the last 30 years, the introduction and acceptance of cytotoxic drugs such as methotrexate and cyclophosphamide have greatly advanced the treatment of patients with severe autoimmune diseases. However, the use and dose escalation of cytotoxic agents in severely ill patients is limited by toxicity and the potential for secondary malignancies that correlate with cumulative lifetime dosing. As hematopoietic stem cell transplant grew to become an established procedure for certain malignancies, reports of remission of coexistent autoimmune diseases began to emerge. Animal data subsequently supported a role for hematopoietic stem cell transplants for the primary indication of autoimmune diseases. On the basis of these reports, clinical trials of hematopoietic stem cell transplants for the primary indication of autoimmune disease were initiated in the late 1990s. We review the data from a decade of experience that has now accumulated for this novel approach to the management of autoimmunity.