Immunohistochemical expression of vascular endothelial growth factor can predict response to 5-fluorouracil and cisplatin in patients with gastric adenocarcinoma.
The combination of 5-fluorouracil (5-FU) and cisplatin is used most commonly for gastric carcinoma. Recent studies have indicated that vascular endothelial growth factor (VEGF) is related to drug delivery through angiogenesis and vascular permeability. In this study, we evaluated the efficacy and toxicity of continuous infusion of 5-FU and low dose cisplatin infusion as first-line treatment in patients with unresectable gastric adenocarcinoma. We also examined the relationship between chemotherapy response and immunohistochemical expression of VEGF in the biopsy samples of gastric primary. All 30 patients enrolled in this study were assessable for response, adverse reactions, and VEGF expression. The regimen consisted of 5-FU (350 mg/m2/day every day by continuous venous infusion) and low dose cisplatin (7 mg/m2/day by drip infusion over 1 h on days 1-5 every week). This treatment was repeated weekly for 3 consecutive weeks. Four weeks after the second cycle, mesurable lesions were estimated for response. An overall response rate was 46.7% (14/30). Patients with intestinal histologic type (10/12) and good performance status ([PS], 13/18) showed good response rate (83.3%, and 72.2%, respectively) compared to patients with diffuse histologic type (4/18) and poor PS [(1/12) 22.2%, and 8. 3%, respectively]. The response rate of VEGF-positive cases and VEGF-negative cases was 75% (12/16), and 16.7% (2/14), respectively. Multivarite analysis revealed that VEGF-positive and good PS had a significant impact on chemotherapy response in this treatment. The most common garde 3 or higher toxicities were myelosuppression (30%) and diarrhea (13.3%). Continuous infusion of 5-FU and low dose cisplatin infusion is an effective treatment for patients with unresectable gastric carcinoma, and VEGF expression may be a useful predictor of chemotherapy response in this regimen.
Takiuchi
H
H
Second Department of Internal Medicine, Osaka Medical College, Osaka 569-8686, Japan.
Hirata
I
I
Kawabe
S
S
Egashira
Y
Y
Katsu
K
K
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001706:Biopsy; D002945:Cisplatin / Q000008:administration & dosage; D016228:Endothelial Growth Factors / Q000032:analysis*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007150:Immunohistochemistry; D007262:Infusions, Intravenous; D008222:Lymphokines / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D015996:Survival Rate; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D002945:Cisplatin; D005472:Fluorouracil