Relationship between expression of vascular endothelial growth factor in tumor tissue from gastric cancers and chemotherapy effects: comparison between S-1 alone and the combination of S-1 plus CDDP.
BACKGROUND
We have reported that vascular endothelial growth factor (VEGF) expression in gastric cancers might be a selective marker between 5-fluorouracil (5-FU) and a combination of 5-FU plus cisplatin (CDDP). In this study, the relationship between VEGF expression and effects of S-1 with and without CDDP is investigated.


METHODS
The subjects were 44 patients treated with S-1 (40 mg/m2, twice daily, days 1-28, repeated every 6 weeks) and 24 patients treated with S-1 plus CDDP (S-1 40 mg/m2, twice daily, days 1-21, CDDP, 60 or 70 mg/m2, day 8, repeated every 5 weeks). VEGF expression in pretreatment endoscopic biopsy samples was assessed immunohistochemically.


RESULTS
Median survival times (MST) of the patients treated with S-1 and S-1 plus CDDP were 344 and 388 days. Among evaluable patients, the response rates of patients with VEGF (+) and (-) tumors to S-1 were 40% (6/15) and 54% (13/24), and to S-1 plus CDDP, 79% (15/19) and 80% (4/5). While the survival of patients with VEGF (-) tumors was slightly longer than those with VEGF (+) tumors in the S-1 group (MST, 425 versus 308 days, P = 0.42), patients with VEGF (+) tumors survived remarkably longer than those with VEGF (-) tumors in the S-1 plus CDDP group (MST, 570 versus 333 days, P = 0.19).


CONCLUSIONS
Similarly to our previous study, it is suggested that the effects of adding CDDP to S-1 might be more remarkable in gastric cancer patients with VEGF (+) tumors than in those with VEGF (-) tumors. These results should be confirmed in a large phase III study.
Boku
Narikazu
N
Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Sunto, Shizuoka, Japan. n.boku@scchr.jp.
Ohtsu
Atsushi
A
Nagashima
Fumio
F
Shirao
Kuniaki
K
Koizumi
Wasaburo
W
D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D002945:Cisplatin / Q000008:administration & dosage; D004338:Drug Combinations; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D010094:Oxonic Acid / Q000008:administration & dosage*; D013274:Stomach Neoplasms / Q000737:chemistry* / Q000188:drug therapy* / Q000401:mortality; D005641:Tegafur / Q000008:administration & dosage*; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis*
D000964:Antimetabolites, Antineoplastic; D014408:Biomarkers, Tumor; D004338:Drug Combinations; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D002945:Cisplatin; D005472:Fluorouracil