Phase I clinical and pharmacokinetic study of RAD001 (everolimus) administered daily to Japanese patients with advanced solid tumors.
OBJECTIVE
To determine the pharmacokinetics and safety of RAD001 (everolimus) in Japanese patients with advanced solid tumors.


METHODS
An open-label, non-randomized, dose-escalation Phase I study of RAD001 administered continuously once daily in a 28-day cycle was performed. The study had a '3 + 3' design, with three patients recruited to each of three successive cohorts treated with RAD001 at 2.5, 5.0 or 10.0 mg/day.


RESULTS
The pharmacokinetics of RAD001 in Japanese patients were similar to those previously determined in Caucasians. The drug safety profile was consistent with that of a mammalian target of rapamycin inhibitor. No dose-limiting toxicities were observed. One patient with esophageal cancer and one with gastric cancer treated with RAD001 at 10 mg/day showed marked tumor responses.


CONCLUSIONS
Treatment of Japanese cancer patients with RAD001 may be undertaken with the expectation that previously determined pharmacokinetic and safety profiles apply. The drug may hold promise for treatment of esophageal and gastric cancer.
Okamoto
Isamu
I
Department of Medical Oncology, Kinki University School of Medicine, 377-2 Ohno-higashi, Osaka-Sayama, Osaka 589-8511, Japan. chi-okamoto@dotd.med.kindai.ac.jp
Doi
Toshihiko
T
Ohtsu
Atsushi
A
Miyazaki
Masaki
M
Tsuya
Asuka
A
Kurei
Katsutoshi
K
Kobayashi
Ken
K
Nakagawa
Kazuhiko
K
D000368:Aged; D044466:Asian People; D015179:Colorectal Neoplasms / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004938:Esophageal Neoplasms / Q000188:drug therapy; D000068338:Everolimus; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary*; D008175:Lung Neoplasms / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009369:Neoplasms / Q000188:drug therapy*; D020123:Sirolimus / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D013274:Stomach Neoplasms / Q000188:drug therapy; D016019:Survival Analysis; D013964:Thyroid Neoplasms / Q000188:drug therapy; D016896:Treatment Outcome
D007166:Immunosuppressive Agents; D000068338:Everolimus; D020123:Sirolimus