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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
All authors: National Cancer Center Hospital, Tokyo, Japan.
Hidenori
H
Mizugaki
All authors: National Cancer Center Hospital, Tokyo, Japan. nbryamam@ncc.go.jp.
Noboru
N
Yamamoto
All authors: National Cancer Center Hospital, Tokyo, Japan.
Yutaka
Y
Fujiwara
All authors: National Cancer Center Hospital, Tokyo, Japan.
Hiroshi
H
Nokihara
All authors: National Cancer Center Hospital, Tokyo, Japan.
Yasuhide
Y
Yamada
All authors: National Cancer Center Hospital, Tokyo, Japan.
Tomohide
T
Tamura
D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002173:Cancer Care Facilities; D017321:Clinical Trials, Phase I as Topic; D017277:Drug Approval; D005260:Female; D006801:Humans; D038622:Internationality; D007564:Japan; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D011379:Prognosis; D012189:Retrospective Studies; D016896:Treatment Outcome; D055815:Young Adult
D000970:Antineoplastic Agents