A phase 3, open-label, multicenter study of a 6-month pre-mixed depot formulation of leuprolide mesylate in advanced prostate cancer patients.

OBJECTIVES: To determine the safety, efficacy and pharmacokinetic (PK) profile of a pre-mixed depot formulation of leuprolide mesylate subcutaneous injectable suspension (LMIS) 50 mg for up to 1 year of treatment for subjects with advanced prostate cancer. PATIENTS AND METHODS: In this open-label, multicenter study, prostate cancer patients with indication for androgen ablation therapy received two subcutaneous injection of LMIS 50 mg 6 months apart and were followed for an additional 6 months. Two efficacy primary end points were the percentage of subjects with a serum testosterone level ≤ 50 ng/dL by Day 28 as well as the percentage of subjects with similar testosterone suppression from Day 28 to Day 336. RESULTS: Of the 137 enrolled subjects, 15 (10.9%) subjects did not complete the study, including 5 subjects who terminated early due to an adverse event. By Day 28, 98.5% (95% confidence interval 94.8-99.8) of the subjects achieved a castrate testosterone level. At the end of the study, 97% and 95.9% of the subjects had serum testosterone level ≤ 50 ng/dL and ≤ 20 ng/dL, respectively. LMIS 50 mg significantly reduced serum prostate-specific antigen levels after its first injection and this PSA declination effect remained until the end of the study. No statistically significant change was observed in worsening bone pain or urinary symptom assessments during the study. Hot flush (48.9%) and hypertension (14.6%) were the two most common adverse events reported. CONCLUSIONS: LMIS 50 mg, administered at 6-month intervals, effectively suppressed serum testosterone level, and demonstrated a consistent safety profile.

Clinical significance of cytologic atypical squamous cells of undetermined significance.

OBJECTIVE: To analyze the screening status, clinical characteristics, and risk of invasive cervical cancer in women with cytologic atypical squamous cells of undetermined significance (ASC-US) in general populations and to make recommendations for these women. METHODS: The 95,309 women with initial cytologic ASC-US from the national cervical cancer screening database in Taiwan were divided into unscreened and screened groups based on their previous screening history. Newly diagnosed invasive cervical cancer cases in the follow-up period were retrieved for analysis. RESULTS: There were 860 cases of invasive cervical cancer during the follow-up period of 556,758 person-years, with an overall incidence rate of 154.5 cases per 100,000 person-years. The incidence was 92.3 and 257.2 cases per 100,000 person-years in the screened and unscreened groups, respectively. Previous screening history was a strong risk predictor of invasive cervical cancer (hazard ratio 2.8, 95% confidence interval 2.4-3.1, P<.001) after adjustments for age, educational status, and hospital setting. Age was also a significant risk factor for developing invasive cervical cancer in the unscreened group but not in the screened group. CONCLUSION: Women with cytologic ASC-US, especially those without a previous Pap test or older women, were more likely to develop invasive cervical cancer and should be followed up aggressively. LEVEL OF EVIDENCE: II.