Phase I/II study of hepatic arterial infusion chemotherapy with gemcitabine in patients with unresectable intrahepatic cholangiocarcinoma (JIVROSG-0301).
OBJECTIVE
No established therapy exists for unresectable intrahepatic cholangiocarcinoma (ICC). We conducted a phase I/II study to ascertain the recommended dose (RD) of hepatic arterial infusion using gemcitabine (GEM) for ICC and to assess the efficacy and safety.


METHODS
For patients with unresectable ICC, GEM was administered through the hepatic artery via the port system as a 30-minute infusion on days 1, 8, and 15 every 4 weeks for 5 cycles. In phase I, dosage for levels 1, 2, and 3 was set at 600, 800, and 1000 mg/m, respectively, and was increased in 3 to 6 patients at a time. Maximum tolerated dose was defined as a dosage resulting in dose-limiting toxicity in 2 of 3 patients or 3 of 6 patients, and RD was estimated during the first cycle. In the phase II, more RD patients were added to assess tumor response and toxicity.


RESULTS
During the phase I, 16 patients were enrolled. Maximum tolerated dose was not reached. Assuming RD at 1000 mg/m, the phase II enrolled a total of 13 patients. The following Grade 3 toxicities were observed: neutropenia 20%, increased gamma-glutamyl transpeptidase 8%, increased aspartate aminotransferase 4%, increased alanine aminotransferase 4%, increased bilirubin 4%, nausea 4%, and fatigue 4%. The tumor response rate was 7.7% (complete response 0, partial response 1, stable disease 8, and progressive disease 4).


CONCLUSIONS
Whereas the toxicity of hepatic arterial infusion with 1000 mg/m GEM for ICC was tolerable, expected efficacy could not be obtained, thus suggesting only minimal activity.
Inaba
Yoshitaka
Y
Aichi Cancer Center Hospital, Nagoya, Japan. 105824@aichi-cc.jp
Arai
Yasuaki
Y
Yamaura
Hidekazu
H
Sato
Yozo
Y
Najima
Mina
M
Aramaki
Takeshi
T
Sone
Miyuki
M
Kumada
Takashi
T
Tanigawa
Noboru
N
Anai
Hiroshi
H
Yoshioka
Tetsuya
T
Ikeda
Masafumi
M
D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D001650:Bile Duct Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000601:surgery; D001653:Bile Ducts, Intrahepatic / Q000187:drug effects* / Q000473:pathology / Q000601:surgery; D018281:Cholangiocarcinoma / Q000188:drug therapy / Q000473:pathology / Q000601:surgery; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006499:Hepatic Artery; D006801:Humans; D007261:Infusions, Intra-Arterial; D008113:Liver Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000601:surgery; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D015996:Survival Rate; D016896:Treatment Outcome; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000093542:Gemcitabine