A phase I study of S-1 treatment with a 3 week schedule in advanced biliary cancer patients with or without hepatic dysfunction.
OBJECTIVE
A 3 week treatment schedule consisting of 2 weeks of S-1 therapy and 1 week of no therapy was introduced to reduce the toxicity and increase the convenience of combination chemotherapy. Hepatic dysfunction (HD) is common in patients with biliary tract cancer. A phase I study was conducted to assess the effects of a 3 week treatment schedule in Asian patients with or without HD.


METHODS
Forty-six patients were stratified into four groups, according to the HD criteria of the National Cancer Institute Organ Dysfunction Working Group. A three dose escalation schema was used.


RESULTS
In the normal hepatic function group, two dose-limiting toxicity (DLT) events occurred among 12 patients at the prespecified maximal dose of 100 mg/m²/day. This dose was thereby established as the maximal tolerable dose (MTD). No DLT events were observed at the predefined maximal dose of 80 mg/m²/day in the mild HD group. In the moderate HD group, two DLT events occurred among five patients treated with 80 mg/m²/day, and the MTD was defined as 70 mg/m²/day. Two of six subjects in the severe HD group experienced DLT events at doses of 60 mg/m²/day and none developed DLT events at 50 mg/m²/day.


CONCLUSIONS
The MTDs for a 3 week schedule of S-1 treatment were defined in patients with or without hepatic dysfunction. A 3 week treatment regimen of S-1 might be a platform for combination with newer cytotoxic agents or biologics.
Yoon
Dok Hyun
DH
Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Songpa-gu, Seoul, 138-736, Korea.
Lee
Hyo Jung
HJ
Hong
Yong Sang
YS
Kim
Kyu-Pyo
KP
Lee
Sung Sook
SS
Lee
Jae-Lyun
JL
Chang
Heung Moon
HM
Ryu
Min-Hee
MH
Kang
Yoon-Koo
YK
Lee
Jung Shin
JS
Kim
Tae Won
TW
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001661:Biliary Tract Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000503:physiopathology*; D008111:Liver Function Tests; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D010094:Oxonic Acid / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D005641:Tegafur / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D004338:Drug Combinations; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid