Effect of Levofloxacin on the Efficacy and Adverse Events in Intravesical Bacillus Calmette-Guerin Treatment for Bladder Cancer: Results of a Randomized, Prospective, Multicenter Study.

BACKGROUND: Although bacillus Calmette-Guerin (BCG) is a standard treatment for high-risk non-muscle-invasive bladder cancer (NMIBC), a high rate of adverse events with a variety of grades remains a difficulty. OBJECTIVE: In this randomized, prospective, multicenter study, we examined whether levofloxacin, given after each intravesical instillation of BCG, could improve its tolerance in patients with intermediate- to high-risk urothelial carcinoma of the bladder without compromising its efficacy. DESIGN, SETTING, AND PARTICIPANTS: Overall, 106 Japanese patients (85 men and 21 women; age: median, 69.5 yr) with primary or recurrent NMIBC were randomized after transurethral resection to induce treatment with intravesical BCG plus levofloxacin (group 1) or BCG alone (group 2). INTERVENTION: Patients who underwent intravesical instillation of BCG were randomized with or without levofloxacin administration. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Adverse events were assessed using the National Cancer Institute-Common Toxicity Criteria version 3.0. Cumulative incidence functions and Kaplan-Meier methods were applied to estimate survival outcomes. RESULTS AND LIMITATIONS: There was no significant difference in baseline characteristics between the groups. The completion rate of group 1 (85.5%) was not significantly lower than that of group 2 (76.5%; p = 0.321). There was no significant difference in the completion rate of patients with pollakisuria, painful micturition, gross hematuria, fever elevation, and others between the groups. The incidence of adverse events in patients with high-grade pollakisuria (7.3% vs 25.4%, p = 0.041) and fever (0% vs 9.1%, p = 0.034) was significantly lower in group 1. The 5-yr progression-free and cancer-specific survival rates were significantly better in group 1. CONCLUSIONS: Prophylactic levofloxacin administration may reduce the severity of adverse events and contribute to better outcomes from BCG intravesical therapy in patients with NMIBC. PATIENT SUMMARY: Levofloxacin administration seems to be a safe and effective therapy for non-muscle-invasive bladder cancer patients treated with bacillus Calmette-Guerin intravesical therapy.

Clinical implication of vascular endothelial growth factor T-460C polymorphism in the risk and progression of prostate cancer.

Vascular endothelial growth factor (VEGF), one of the most potent angiogenic factors, is suggested to play a crucial role in tumor neovascularization and is associated with tumor progression and metastasis in prostate cancer. This study evaluated the significance of the VEGF T-460C polymorphism in the risk and the progression of prostate cancer. In a case-control experiment, 270 patients with prostate cancer and 252 male controls were investigated to assess the association of the VEGF T-460C polymorphism with the risk of prostate cancer. Prostate-specific antigen (PSA) recurrence in 95 patients who underwent radical prostatectomy and survival in 99 patients with metastases at diagnosis were analyzed to evaluate the influence of the polymorphism in cancer progression. The CC and TC genotypes of the polymorphism were associated with significantly higher rates of PSA recurrence after radical prostatectomy than the TT genotype and were independent predictors of PSA recurrence (P=0.011) in a multivariate analysis. In contrast, metastatic prostate cancer patients with the TT genotype showed significantly worse survival as compared to the CC and TC genotypes. In a multivariate analysis, the TT genotype was an independent predictor of cancer-specific survival (P=0.006). The VEGF T-460C polymorphism may have a substantial impact on both PSA recurrence after radical prostatectomy and survival in advanced prostate cancer. The molecular mechanisms of the polymorphism on the differing status in prostate cancer should be elucidated in further studies.

Impact of IGF-I and CYP19 gene polymorphisms on the survival of patients with metastatic prostate cancer.

PURPOSE: The prognosis of metastatic prostate cancer significantly differs among individuals. While various clinical and biochemical prognostic factors for survival have been suggested, the progression and response to treatment of those patients may also be defined by host genetic factors. In this study, we evaluated genetic polymorphisms as prognostic predictors of metastatic prostate cancer. PATIENTS AND METHODS: One hundred eleven prostate cancer patients with bone metastasis at the diagnosis were enrolled in this study. Thirteen genetic polymorphisms were genotyped using polymerase chain reaction-restriction fragment length polymorphism or an automated sequencer with a genotyping software. RESULTS: Among the polymorphisms, the long allele (over 18 [CA] repeats) of insulin-like growth factor-I (IGF-I) and the long allele (over seven [TTTA] repeats) of cytochrome P450 (CYP) 19 were significantly associated with a worse cancer-specific survival (P = .016 and .025 by logrank test, respectively). The presence of the long allele of either the IGF-I or CYP19 polymorphisms was an independent risk factor for death (P = .019 or .026, respectively). Furthermore, the presence of the long allele of both the IGF-I and CYP19 polymorphisms was a stronger predictor for survival (P = .001). CONCLUSION: The prognosis of metastatic prostate cancer patients is suggested to be influenced by intrinsic genetic factors. The IGF-I (CA) repeat and CYP19 (TTTA) repeat polymorphisms may be novel predictors in prostate cancer patients with bone metastasis at the diagnosis.

[Two cases of urothelial cancer responsive to high-dose-intensity methotrexate vinblastine doxorubicin and cisplatin (M-VAC) therapy].

We report two cases of metastatic urothelial cancer treated with high-dose-intensity (HD) methotrexate vinblastine, doxorubicin and cisplatin (MVAC). After HD-MVAC, the size of primary and lymph node tumors decreased by 57-67% as compared with the standard M-VAC therapy. By shortening the dose interval, HD-MVAC may increase the anti-tumor effect without increasing side effects.