Biological markers as a predictor for response and prognosis of unresectable gastric cancer patients treated with irinotecan and cisplatin.
BACKGROUND
Previously we reported that immunohistochemical examination of p53, bcl-2, glutathione S-transferase-pi (GST-pi), thymidylate synthase (TS) and vascular endothelial growth factor (VEGF) in biopsy samples was a useful method for predicting clinical outcome of gastric cancer patients treated with 5-fluorouracil and cisplatin. Here, we investigated if these biological markers can predict chemoresponse and survival of unresectable gastric cancer patients treated with irinotecan and cisplatin.


METHODS
The subjects were 55 unresectable gastric cancer patients treated with irinotecan (70 mg/m(2), Days 1 and 15) and cisplatin (80 mg/m(2), Day 1). Expression of p53, bcl-2, VEGF was examined immunohistochemically in biopsy samples.


RESULTS
The overall response rate and the median survival time were 55% (30/55) and 321 days, respectively. Thirty patients with intestinal-type adenocarcinoma survived longer than 25 patients with diffuse-type (median survival time: 446, 259 days, P = 0.013). The favorable phenotypes for chemoresponse were p53-negative, bcl-2-negative and VEGF-positive, which were in accordance with previous findings. The response rate was significantly correlated with the total number of these favorable phenotypes (P = 0.043). The 39 patients having 2 or 3 favorable phenotypes (p53-negative, bcl-2-negative and VEGF-positive) survived longer than the remaining 16 patients (median survival time: 444, 259 days, P = 0.021). In the Cox model, the number of the favorable phenotypes showed a tendency to correlate with survival after adjustment for potentially prognostic factors such as histological type or performance status (P = 0.070).


CONCLUSIONS
Immunohistochemical examination of biological markers may be useful in predicting the clinical outcome of unresectable gastric cancer patients treated with irinotecan and cisplatin.
Nagashima
Fumio
F
Division of Digestive Endoscopy and Gastrointestinal Oncology, National Cancer Center Hospital East, Chiba, Japan. fnagashi@saitama-med.ac.jp
Boku
Narikazu
N
Ohtsu
Atsushi
A
Yoshida
Shigeaki
S
Hasebe
Takahiro
T
Ochiai
Atsushi
A
Sakata
Yu
Y
Saito
Hiroshi
H
Miyata
Yoshinori
Y
Hyodo
Ichinosuke
I
Ando
Masahiko
M
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D002945:Cisplatin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005260:Female; D051549:Glutathione S-Transferase pi / Q000032:analysis; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis
D014408:Biomarkers, Tumor; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D042461:Vascular Endothelial Growth Factor A; D000077146:Irinotecan; D051549:Glutathione S-Transferase pi; D002945:Cisplatin; D002166:Camptothecin