PURPOSE Pazopanib is an oral angiogenesis inhibitor targeting vascular endothelial growth factor receptor, platelet-derived growth factor receptor, and c-Kit. This randomized, double-blind, placebo-controlled phase III study evaluated efficacy and safety of pazopanib monotherapy in treatment-naive and cytokine-pretreated patients with advanced renal cell carcinoma (RCC). PATIENTS AND METHODS Adult patients with measurable, locally advanced, and/or metastatic RCC were randomly assigned 2:1 to receive oral pazopanib or placebo. The primary end point was progression-free survival (PFS). Secondary end points included overall survival, tumor response rate (Response Evaluation Criteria in Solid Tumors), and safety. Radiographic assessments of tumors were independently reviewed. Results Of 435 patients enrolled, 233 were treatment naive (54%) and 202 were cytokine pretreated (46%). PFS was significantly prolonged with pazopanib compared with placebo in the overall study population (median, PFS 9.2 v 4.2 months; hazard ratio [HR], 0.46; 95% CI, 0.34 to 0.62; P < .0001), the treatment-naive subpopulation (median PFS 11.1 v 2.8 months; HR, 0.40; 95% CI, 0.27 to 0.60; P < .0001), and the cytokine-pretreated subpopulation (median PFS, 7.4 v 4.2 months; HR, 0.54; 95% CI, 0.35 to 0.84; P < .001). The objective response rate was 30% with pazopanib compared with 3% with placebo (P < .001). The median duration of response was longer than 1 year. The most common adverse events were diarrhea, hypertension, hair color changes, nausea, anorexia, and vomiting. There was no evidence of clinically important differences in quality of life for pazopanib versus placebo. CONCLUSION Pazopanib demonstrated significant improvement in PFS and tumor response compared with placebo in treatment-naive and cytokine-pretreated patients with advanced and/or metastatic RCC.

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The nadir PSA level after hormone therapy may be the most accurate factor predicting the progression to hormone refractory prostate cancer and is an independent prognostic factor for survival. Furthermore, a lower limit for the nadir PSA level of 1.1 ng./ml. gives optimal sensitivity and specificity.

The rising rates of prostate cancer in South Korea cannot be attributed entirely to PSA screening due to the low PSA screening prevalence; this trend is most likely related to increased westernization among Koreans. Interdisciplinary epidemiological studies incorporating the collection of biological samples are needed to clarify the extent to which lifestyle and genetic factors contribute to the observed racial disparity.

OBJECTIVES To investigate the roles of glutathione and glutathione‐S‐transferase (GST) in cisplatin‐resistance mechanisms in human bladder cancer, by using glutathione‐depleting or GST‐blocking agents. MATERIALS AND METHODS Cisplatin‐resistant human bladder cancer cell lines were established by continuous exposure of T24 cells to increasing concentrations of cisplatin. Buthionine sulphoximine (BSO), ethacrynic acid and indomethacin were used to deplete glutathione or block GST. Intracellular glutathione content, GST activity and cisplatin cytotoxicity were determined after exposing parental and drug‐resistant cell lines to these agents. RESULTS Intracellular glutathione content and GST activity were significantly decreased, and cisplatin cytotoxicity significantly enhanced, in both parental and resistant cell lines by glutathione‐depleting or GST‐blocking agents. However, the resistance of cisplatin‐resistant cell lines did not fully recover to that of the parental cells with combined BSO and indomethacin. CONCLUSIONS Both increased glutathione content and GST activity are significant in the cisplatin resistance of human bladder tumour cells. Because BSO, ethacrynic acid and indomethacin caused a partial recovery of resistance in the cisplatin‐resistant cell line, further studies are needed to investigate their efficacy for treating patients with metastatic bladder carcinoma resistant to cisplatin.