Investigator initiated clinical trial of remdesivir for the treatment of COVID-19 in Japan.

Coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) originating in Wuhan, China, has spread globally very rapidly. The number of COVID-19 patients increased in Japan from late March to early April 2020. Since COVID-19 treatment methods with antiviral drugs were not established in March 2020, clinical trials began at a rapid pace worldwide. We participated in a global investigator-initiated clinical trial of the antiviral drug remdesivir. It took approximately two months to prepare for and start patient enrollment, 26 days to enroll all patients in Japan, and 32 days from the end of enrollment to the release of the first report, a fairly quick response overall. In the course of this clinical trial, we found some of the critical issues related to conducting an infectious disease clinical trial in Japan need to be addressed and tackled to support a rapid response. These included such things as the necessity of a research network to promote clinical research, a framework for a rapid review system of clinical trial notification, and better cooperation with outsourced teams. Furthermore, for Japan to take the lead in global collaborative research and development in the field of infectious diseases, it is necessary to develop further human resources and organization on a national basis. It is indispensable for Japan to establish a clinical trial system at the national level to prepare for future emerging and re-emerging infectious diseases.

[A three-week regimen of S-1 monotherapy reduced gastrointestinal toxicity and maintained efficacy in patients with gemcitabine-refractory advanced pancreatic cancer].

S-1 administration for 28 consecutive days followed by 14 days of rest (6-week cycle) is often chosen as second-line chemotherapy for advanced pancreatic cancer (PC), but it causes gastrointestinal toxicity. In comparison, in gastric cancer or head and neck cancer, S-1 administration for 14 consecutive days followed by a 7-day rest period (3-week cycle) reduced gastrointestinal toxicity. This study retrospectively evaluated the efficacy and safety of a 3-week S-1 schedule compared to a 6-week schedule in patients with gemcitabine (GEM)-refractory advanced PC. Fifty-seven patients were treated with the 6- week S-1 schedule and 68 patients were treated with the 3-week S-1 schedule. There were no statistical differences in overall survival (p=0.13) and progression-free survival (p=0.190). With regard to adverse events, the rates of nausea (p<0.01) and vomiting (p=0.04) were lower with the 3-week schedule than with the 6-week schedule. Thus, S-1 therapy with a 3- week schedule as second-line chemotherapy in patients with GEM-refractory advanced PC was associated with reduced gastrointestinal toxicity and similar efficacy, when compared to a 6-week schedule.

Efficacy of prophylactic minocycline treatment for skin toxicities induced by erlotinib plus gemcitabine in patients with advanced pancreatic cancer: a retrospective study.

BACKGROUND: Erlotinib has been reported as being associated with a high incidence of skin toxicities such as acneiform rash, paronychia, and xerosis. OBJECTIVE: The aim of this study was to evaluate the efficacy of prophylactic minocycline treatment for the skin toxicities induced by erlotinib as compared with deferred minocycline treatment in patients with pancreatic cancer treated with erlotinib plus gemcitabine. METHODS: A total of 96 patients were studied retrospectively, of whom 44 received prophylactic minocycline between August 2012 and June 2013 and 52 received deferred minocycline treatment between August 2011 and July 2012 at the National Cancer Center Hospital East, Kashiwa, Japan. In the prophylactic minocycline group, 200 mg/day oral minocycline was prophylactically administered during the treatment period. RESULTS: The incidence rate of acneiform rash and xerosis of any grade during the first 6 weeks of treatment was significantly reduced in the prophylactic minocycline group compared with the deferred minocycline treatment group (47.7 vs. 80.8%, p<0.001; 2.3 vs. 19.2%, p=0.01). Multivariate analysis identified prophylactic minocycline as a significant independent factor associated with the incidence of acneiform rash and xerosis of any severity (odds ratio [OR] 0.16, 95% confidence interval [CI] 0.06-0.46, p<0.001; OR 0.11, 95% CI 0.01-0.90, p=0.04). CONCLUSION: Prophylactic minocycline appears to be useful for the management of erlotinib-related acneiform rash and xerosis during chemotherapy in patients with advanced pancreatic cancer.