Efficacy and Safety of DA-8010, a Novel M3 Antagonist, in Patients With Overactive Bladder: A Randomized, Double-Blind Phase 2 Study / 대한배뇨장애요실금학회지

Purpose@#DA-8010 is a novel muscarinic M3 receptor antagonist with significant selectivity for bladder over salivary gland in preclinical studies. We evaluated the clinical efficacy and safety of DA-8010 in overactive bladder (OAB) patients. @*Methods@#This phase 2, randomized, double-blind, parallel-group, active reference- and placebo-controlled trial was conducted at 12 centers in South Korea (NCT03566134). Patients aged ≥19 years with OAB symptoms for ≥3 months were enrolled. Three hundred six patients (30.07% male) were randomized to 12 weeks of treatment among 4 groups; 2 experimental groups (DA-8010 2.5 or 5 mg), an active reference group (solifenacin 5 mg), and a placebo group. The change from the baseline of (=∆) 24-hour frequency at 12 weeks (primary endpoint), episodes of urgency, overall/urgency urinary incontinence, average/ maximum voided volume, nocturia, and patients’ subjective responses were analyzed. @*Results@#In the full analysis set, the mean (standard deviation) [median] values for ∆ 24-hour frequency at 12 weeks were -1.01 (2.44) [-1.33] for placebo, -1.22 (2.05) [-1.33] for DA-8010 2.5 mg, and -1.67 (2.25) [-1.67] for DA-8010 5 mg; DA-8010 5 mg showed a significant decrease compared with placebo (P=0.0413). At 4 and 8 weeks, both DA-8010 2.5 mg (P=0.0391 at 4 weeks, P=0.0335 at 8 weeks) and DA-8010 5 mg (P=0.0001 at 4 weeks, P=0.0210 at 8 weeks) showed significant decrease in ∆ 24-hour frequency compared with placebo. DA-8010 5 mg achieved a significant decrease in ∆ number of urgency episodes, compared with placebo at 4 (P=0.0278) and 8 (P=0.0092) weeks. Adverse drug reactions (ADRs) were observed in 3.95% of placebo, 6.67% of DA-8010 2.5 mg, 18.42% of DA-8010 5 mg, and 17.33% of solifenacin 5 mg groups. No serious ADRs were observed in any patient. @*Conclusions@#Both DA-8010 2.5 mg and 5 mg showed therapeutic efficacy for OAB without serious ADRs. Therefore, both dosages of DA-8010 can advance to a subsequent large-scale phase 3 trial.

Which Patients Should We Follow up beyond 5 Years after Definitive Therapy for Localized Renal Cell Carcinoma? / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Up to 10% of recurrences develop beyond 5 years after curative treatment of localized renal cell carcinoma (RCC). Clinicopathologic features were evaluated to determine which factors are associated with late recurrence. MATERIALS AND METHODS: A total of 753 patients were diagnosed with localized RCC from January 2000 to June 2008. We enrolled 225 patients who were treated surgically and had a minimal recurrence-free survival of 60 months. Patients who had recurrence beyond 5 years after nephrectomy were defined as the late recurrence group and the remaining patients as the recurrence-free group. Multivariate logistic regression analyses and the Cox proportional hazard model were used for determination of features associated with late recurrence. RESULTS: In multivariate analyses, age older than 60 (p=0.030), Fuhrman grade > or = 3 (p=0.042), and pT stage > or = pT2 (p=0.010) showed statistical association with late recurrence. The Cox proportional hazard model showed significant differences in recurrence-free survival when we classified the patients based on pT2 (p=0.007) and on patient age > or = 60 years (p=0.039). CONCLUSION: Patient age greater than 60 years, Fuhrman grade > or = 3, and tumor stage > or = pT2 are independent risk factors of recurrence more than 5 years after surgery in patients with RCC. Therefore, close lifelong follow-up is recommended for patients with these risk factors.

Factors Affecting the Time to Recurrence After Radical Nephrectomy for Localized Renal Cell Carcinoma

PURPOSE: The objective of this study was to determine the factors affecting the time to recurrence after radical nephrectomy for localized renal cell carcinoma. MATERIALS AND METHODS: We retrospectively evaluated 321 patients who received radical nephrectomies for localized renal cell carcinoma (pT1a-pT2b N0M0). Of 29 patients with disease recurrence, 9 had recurrence more than 5 years after radical nephrectomy. We evaluated the clinicopathological factors, with the use of a retrospective study design. RESULTS: Tumor necrosis was statistically different between the late recurrence group and the recurrence free group (Fisher exact test, p=0.046). Hematuria at diagnosis (chi-square test, p=0.045) was statistically significant in early recurrence. In the univariate logistic regression analysis, tumor necrosis (odds ratio [OR], 4.629; 95% confidence interval [CI], 1.106 to 19.379; p=0.036) and pT stage>1 (OR, 7.232; 95% CI, 1.727 to 30.280; p=0.007) were risk factors of late recurrence. In the multivariable logistic regression analysis, pT stage>1 (OR, 7.143; 5% CI 1.706 to 29.912, p=0.007) was associated with late recurrence. Regarding early recurrence, initial symptoms at diagnosis and pathologic T stage>1 were statistically significant in both univariate and multivariable logistic regression analysis. In terms of recurrence site, patients with late recurrence tended to have unusual metastasis sites other than lung, liver or bone (chi-square test, p=0.012). CONCLUSIONS: These data suggest that tumor necrosis may affect late disease recurrence. Patients with initial symptoms and hematuria at diagnosis are vulnerable to recurrence in a shorter period after nephrectomy. Patients with late recurrence showed a tendency to have unusual metastasis site other than lung, liver or bone.