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Japanese Journal of Clinical Oncology Advance Access originally published online on November 22, 2005
Japanese Journal of Clinical Oncology 2005 35(12):714-719; doi:10.1093/jjco/hyi194
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© 2005 Foundation for Promotion of Cancer Research

Biological Markers as a Predictor for Response and Prognosis of Unresectable Gastric Cancer Patients Treated with Irinotecan and Cisplatin

Fumio Nagashima1, Narikazu Boku1, Atsushi Ohtsu1, Shigeaki Yoshida1, Takahiro Hasebe2, Atsushi Ochiai2, Yu Sakata3, Hiroshi Saito4, Yoshinori Miyata5, Ichinosuke Hyodo6 and Masahiko Ando7

1 Division of Digestive Endoscopy and Gastrointestinal Oncology, National Cancer Center Hospital East, 2 Pathology Division, National Cancer Center Research Institute East, Kashiwa, Chiba, 3 Department of Internal Medicine, Misawa City Hospital, Aomori, 4 Department of Medicine, Yamagata Prefectural Central Hospital, Yamagata, 5 Department of Medicine, Saku General Hospital, Nagano, 6 Department of Internal Medicine, National Shikoku Cancer Center, Matsuyama and 7 Health Service, Kyoto University, Kyoto, Japan

For reprints and all correspondence: Fumio Nagashima, MD, Department of Clinical Oncology, Saitama Medical School, 38 Morohongo, Moroyamama, Iruma-gun, Saitama, 350-0495, Japan. E-mail: fnagashi{at}saitama-med.ac.jp

Received June 23, 2005; accepted October 9, 2005

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/m2, Days 1 and 15) and cisplatin (80 mg/m2, 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.

Key Words: gastric cancer • chemotherapy • p53 • bcl-2 • VEGF


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