Drug use investigation on the safety and efficacy of tigecycline in Japan (all-case post-marketing surveillance).

INTRODUCTION: We conducted a drug use investigation to investigate the safety and efficacy of tigecycline, which has been approved for clinical use for the treatment of multidrug-resistant gram-negative infections in Japan. METHODS: This was an open-label, observational, multicenter cohort study that included all patients who received tigecycline. RESULTS: A total of 116 patients were registered between December 2012 and April 2016 and all of them were evaluated for safety and efficacy. Among them, 64 patients aged ≥65 years (55.2%) and five children aged <15 years (4.3%) were included. Of these patients, 47 (40.5%) met the approved indications of tigecycline. Adverse drug reactions (ADRs) were observed in 41 patients (35.3%) with a total of 74 events. Serious ADRs were observed in 15 patients (12.93%) with a total of 33 events. There were 42 deaths, and 6 of these were considered to be caused by ADRs. Among the 116 patients, 65 achieved clinical response at the end of the observation period, and the efficacy rate was 73.9%. Furthermore, 46 patients were assessed as "cure" at the test of cure visit, and the cure rate was 59.0%. The eradication rate was 47.5% at the end of the observation period. Classified by pathogenic bacteria, the eradication rate of patients infected with the approved pathogens was 54.5%. CONCLUSIONS: Tigecycline was well-tolerated, and no additional safety concerns were noted. It was effective considering that most patients had poor physical conditions. The overall benefit-risk balance of tigecycline was favorable.

Real-world use of temsirolimus in Japanese patients with unresectable or metastatic renal cell carcinoma: recent consideration based on the results of a post-marketing, all-case surveillance study.

OBJECTIVE: A prospective, observational, post-marketing surveillance was conducted to assess the safety and effectiveness of temsirolimus in patients with renal cell carcinoma in Japan. METHODS: Patients prescribed temsirolimus for advanced renal cell carcinoma were registered and received temsirolimus (25 mg weekly, intravenous infusion for 30-60 minutes) in routine clinical settings (observation period: 96 weeks). RESULTS: Among 1001 patients included in the safety analysis data set (median age, 65.0 years; men, 74.8%; Eastern Cooperative Oncology Group performance status 0 or 1, 69.6%), 778 (77.7%) reported adverse drug reactions. The most common (≥10%) all-grade adverse drug reactions were stomatitis (26.7%), interstitial lung disease (17.3%) and platelet count decreased (11.1%). The incidence rate of grade ≥3 interstitial lung disease was 4.5%. The onset of interstitial lung disease was more frequent after 4-8 weeks of treatment or in patients with lower Eastern Cooperative Oncology Group performance status (21.6% for score 0 vs 8.3% for score 4, P < 0.001). Among 654 patients in the effectiveness analysis data set, the response and clinical benefit rates were 6.7% (95% confidence interval 4.9-8.9) and 53.2% (95% confidence interval 49.3-57.1), respectively. The median progression-free survival was 18.3 weeks (95% confidence interval 16.9-21.1). CONCLUSIONS: The safety and effectiveness profile of temsirolimus observed in this study was similar to that observed in the multinational phase 3 study. The results are generalizable to the real-world scenario at the time of this research, and safety and effectiveness of temsirolimus as a subsequent anticancer therapy for renal cell carcinoma warrants further investigation. (ClinicalTrials.gov identifier NCT01210482, NCT01420601).