Bacillus Calmette-Guérin versus gemcitabine for intravesical therapy in high-risk superficial bladder cancer: a randomised prospective study.
ABSTRACT To evaluate the safety, tolerability and efficacy of adjuvant intravesical gemcitabine versus bacillus Calmette-Guérin (BCG) in the treatment of high-risk superficial bladder cancer.
64 patients with high-risk superficial bladder cancer (pT1 and/or G3 and/or CIS) were assigned to interventions (gemcitabine or BCG) in a randomised controlled trial. All the patients were evaluated for recurrence and progression rates (primary endpoint) and safety and tolerability (secondary endpoint).
The two groups were comparable in terms of baseline characteristics. Tolerability was better for gemcitabine, whereas the BCG group experienced the need for delayed treatment or withdrawal in 12.5% of cases. At a mean follow-up of 44 months, the recurrence rate in patients treated with BCG was 28.1%; the recurrence rate in patients who received gemcitabine was 53.1% (p = 0.037). Time to recurrence was shorter in patients treated with BCG (25.6 vs. 39.4 months, p = 0.042). No patients developed disease progression.
Gemcitabine is significantly inferior to BCG, but given its favourable toxicity profile, it may be useful for patients intolerant to or otherwise unable to receive BCG.
- SourceAvailable from: Anja Mehnert[Show abstract] [Hide abstract]
ABSTRACT: PURPOSE: BCG and intravesical chemotherapy represent viable adjuvant options in intermediate-risk non-muscle-invasive bladder cancer (NMIBC). Although BCG is perceived as less tolerable than intravesical chemotherapy, no comparative studies have addressed quality of life (QoL) issues. We compared QoL of NMIBC patients who received either adjuvant intravesical gemcitabine or 1/3 dose BCG. MATERIAL AND METHODS: our multicenter, prospective, randomised, phase II study included 120 intermediate-risk NMIBC; 88 remained assessable at 1-year follow-up. Only one patient was withdrawn because of adverse events. 61 patients received gemcitabine 2000 mg/50 cc weekly for 6 weeks (maintenance monthly for one year), while 59 BCG Connaught 1/3 dose weekly for 6 weeks (maintenance 3 weekly instillations at 3, 6 and 12 months). QoL was measured by EORTC QlQ-C30 and BLS-24 questionnaires. Group differences were calculated using analysis of variance (ANOVA/MANOVA). RESULTS: treatment was well-tolerated in both groups, although local and systemic side-effects were more frequent in the BCG-arm. Multivariable analyses showed no significant differences between the two groups in all QoL dimensions. No significant changes over time in QoL domains were detected for both BCG and gemcitabine patients, except for Physical Functioning, which significantly decreased in both groups (p 0.002). No significant differences were detected in terms of recurrence and progression between the two groups at 1 year follow-up. CONCLUSIONS: while a higher rate of side effects, albeit mild to moderate, was detected with 1/3 dose BCG as compared to gemcitabine, our study failed to show significant differences between the two drugs in terms of QoL.The Journal of urology 03/2013; · 3.75 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Approximately 70% of newly diagnosed bladder tumors are non-muscle invasive bladder cancer (NMIBC). NMIBC accounts for approximately 80% of total bladder cancer cases. Bacillus Calmette-Guérin (BCG) instillation and maintenance is considered as the standard adjuvant treatment for superficial bladder cancer. A number of randomized studies have focused on the benefit of maintenance therapy following initial BCG induction. To provide further insights into the effect of intravesical instillation on recurrence in patients with NMIBC, we analyzed this relationship by conducting an updated detailed meta-analysis. Evidence suggested that adjuvant intravesical BCG with maintenance treatment is significantly effective for the prophylaxis of tumor recurrence in patients with NMIBC.Frontiers of medicine. 05/2014;
- [Show abstract] [Hide abstract]
ABSTRACT: B7-H4 is a recently identified member of the B7 family considered to negatively regulate the immune response, and has been associated with the occurrence and development of certain types of tumor. However, little is known regarding the importance of human B7-H4 expression in bladder urothelial carcinoma. In the present study, B7-H4 expression in the tissues and sera of patients with bladder urothelial carcinoma was investigated, along with the clinical significance. In addition, the effects of activated T-lymphocyte in vitro cytotoxicity in the BIU-87 bladder cancer cell line following the blockade of the B7-H4 signaling pathway were also analyzed. The results showed that in normal bladder tissues, B7-H4 was not detected, but in the bladder urothelial carcinoma tissue samples, B7-H4 was detected in 24/49 (49.0%) specimens. Additionally, positive B7-H4 expression was significantly associated with increased TNM stage and pathological grade (P<0.05). Compared with the healthy control group, the serum-B7-H4 (sB7-H4) concentrations in the patients were also significantly increased (P<0.05). The sB7-H4 concentrations in cases with high-grade histology were significantly higher than those in patients with low-grade histology (P<0.05). Following the blockade of the B7-H4 antigen in BIU-87 cells, the cytotoxic activity of activated T cells against such BIU-87 cells was significantly enhanced compared with that against the control BIU-87 cells. This occurred in a T cell density-dependent and blocking antibody dose-dependent manner. These observations suggest that B7-H4 is involved in tumor occurrence, and the development and immune escape of bladder urothelial carcinoma cells. Therefore, B7-H4 may be an important target in the diagnosis and/or treatment of bladder urothelial carcinoma.Oncology letters 12/2014; 8(6):2527-2534. · 0.24 Impact Factor