Current Status of Single-Agent Phase I Trials in Japan: Toward Globalization

In Japan, phase I trials, except first-in-human trials, are usually initiated from approximately 50% of the maximum-tolerated dose (MTD) or maximum administered dose (MAD) determined during the initial phase I trials in North America and Europe (the West). However, the key findings of phase I trials in Japan and the West, such as dose-limiting toxicity (DLT) profiles and MTD or MAD levels, have not been compared.

We retrospectively analyzed data for patients enrolled onto single-agent phase I trials at the National Cancer Center Hospital between 1995 and 2012. DLT profiles, MTDs, and MADs of single-agent phase I trials in Japan were compared with those from trials in the West that were obtained from the literature.

A total of 777 patients were enrolled onto 54 single-agent phase I trials, including five first-in-human trials. DLTs were observed in 11.1% of the patients. Importantly, 66.4% of the DLTs were observed within a dose range (80% to 120%) similar to those reported for the trials in the West. The majority of MTDs or MADs could be considered similar between patients, and 80.3% of the drugs had similar MTDs or MADs in the West.

The toxicity profiles of single-agent phase I agents determined from trials conducted in Japan were comparable to those obtained from trials in the West. We believe that phase I trials in Japan could be conducted over timelines similar to those in the West, allowing for global or parallel phase I clinical trials.