A phase II Study of the global dose and schedule of capecitabine in Japanese patients with metastatic colorectal cancer.
BACKGROUND
Although the standard 3-week capecitabine regimen (1250 mg/m(2) twice daily for 2 weeks followed by a 1-week rest) has shown superior activity and improved safety over bolus 5-fluorouracil/leucovorin in two large randomized phase III trials in Europe and in the United States, only a 4-week regimen of capecitabine (828 mg/m(2) twice daily for 3 weeks) has been studied in Japan. Therefore, we performed a phase II study to investigate the 3-week regimen of capecitabine in Japanese patients with metastatic colorectal cancer (MCRC).


METHODS
Previously untreated patients with MCRC received oral capecitabine 1250 mg/m(2) twice daily for 2 weeks. Treatment was repeated every 3 weeks. Blood and urine samples were collected for pharmacokinetic analysis.


RESULTS
Sixty patients were enrolled. The overall response rate was 35% [95% confidence interval (CI), 23-48%], and 52% of patients had stable disease. The median time to progression was 5.5 months (95% CI, 4.2-6.7 months). The median overall survival was 20.2 months (95% CI, 16.6-27.8 months). The most frequently occurring adverse drug reaction was hand-foot syndrome (all-grade 73%; grade 3 13%). Diarrhea, anorexia, nausea and stomatitis were each seen in 37% of patients. The pharmacokinetic profiles of capecitabine and its metabolites were similar to those reported in Caucasian patients.


CONCLUSIONS
The 3-week regimen of capecitabine was effective and well tolerated in Japanese patients with MCRC as well, and could be used as the basic regimen for future combination therapies.
Hyodo
Ichinosuke
I
Division of Gastroenterology, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan. ihyodo@md.tsukuba.ac.jp
Shirao
Kuniaki
K
Doi
Toshihiko
T
Hatake
Kiyohiko
K
Arai
Yasuaki
Y
Yamaguchi
Kensei
K
Tamura
Takao
T
Takemiya
Shoji
S
Takiuchi
Hiroya
H
Nakagawa
Kazuhiko
K
Mishima
Hideyuki
H
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000069287:Capecitabine; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D004334:Drug Administration Schedule; D023381:Endpoint Determination; D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives; D006801:Humans; D008113:Liver Neoplasms / Q000556:secondary; D008175:Lung Neoplasms / Q000556:secondary; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil