Is gemcitabine an option in BCG-refractory nonmuscle-invasive bladder cancer? A single-arm prospective trial.

The objective of this study was to evaluate intravesical gemcitabine in high-risk nonmuscle-invasive bladder cancer (NMIBC) refractory to bacillus Calmette-Guérin (BCG). This was a prospective multicentre single-arm trial. Eligible patients were those with high-risk NMIBC refractory to BCG therapy, for which radical cystectomy was indicated but not conducted because of patient refusal or ineligibility. Patients received intravesical gemcitabine twice weekly at a dose of 2000 mg/50 ml for 6 weeks, and then weekly for 3 weeks at 3, 6, and 12 months. Outcome measures were recurrence rate, time to first recurrence, progression rate and complications. Twenty patients were enrolled and included in the analysis. Median follow-up was 15.2 months. Fifty-five percent (11 patients) developed disease recurrence. Mean time to the first recurrence was 3.5 months and 45% (five patients) of recurring patients had disease progression. Overall, treatment was well tolerated. Urinary symptoms represented the primary adverse events. The role of gemcitabine used as second-line treatment in high-risk BCG-refractory NMIBC patients who refused or were unsuitable for radical cystectomy remains to be defined. Further clinical research in this area is needed.

Phase II study of sorafenib in patients with sunitinib-refractory metastatic renal cell cancer.

PURPOSE: No previous prospective trials have been reported with sorafenib in patients with sunitinib-refractory metastatic renal cell cancer (MRCC). We conducted a multicenter study to determine the activity and tolerability of sorafenib as second-line therapy after sunitinib progression in MRCC. PATIENTS AND METHODS: Between January 2006 and September 2008, 52 patients were enrolled onto this single-arm phase II study. All patients received sorafenib 400 mg orally twice a day until disease progression or intolerable toxicity. The primary end point was objective response rate (complete or partial response) evaluated every 8 weeks by use of the Response Evaluation Criteria in Solid Tumors; secondary end points were toxicity, time to progression (TTP), and overall survival (OS). RESULTS: All patients were included in response and safety analyses. Partial responses were observed in 9.6% of patients (five of 52 patients; 95% CI, 5% to 17%) after two cycles. Grade 1 to 2 fatigue, diarrhea, nausea/vomiting, rash, and neutropenia were the most common side effects, noted in 16 (30.8%), 19 (36.5%), 20 (38.5%), 19 (36.5%), and 20 patients (38.5%), respectively. The most common grade 3 toxicity was diarrhea, noted in six patients (11.5%). Median TTP was 16 weeks (range, 8 to 40 weeks), and median OS was 32 weeks (range, 16 to 64 weeks). CONCLUSION: Although well tolerated, sorafenib shows limited efficacy in sunitinib-refractory MRCC. Further randomized trials comparing sorafenib with other drugs that target different biologic pathways are needed to define the best second-line treatment option in these patients.