Gastrointestinal Oncology

Introduction
The Gastrointestinal Oncology Division currently focuses on chemotherapy with or without radiation therapy against gastrointestinal malignancies. We treat many patients, and participate in various clinical studies to develop a new or standard treatment prospectively. We also investigate the relationship among clinicopathological features, biological characteristics and clinical outcomes of each treatment for the purpose of developing treatment-oriented diagnosis and stratification or individualization of treatment.

Routine Activities 
We participate in many clinical studies. The number of inpatients has been increasing year by year. We provide outpatient-based chemotherapy for suitable candidates including new patients. Thus, more than 20 patients receive chemotherapy everyday. The average hospital stay of patients treated with chemotherapy or palliative therapy was as short as 13.5 (median, 8) days. The most appropriate treatments for all patients are determined in case conferences consisting of medical, surgical, radiation oncologists, and diagnostic radiologists, and are initiated after obtaining patients' informed consent.

New Developments
1. Esophageal Cancer
A phase II study of chemoradiotherapy (CRT) with 5-FU + CDDP + RT for stage II/III esophageal cancer has been completed (JCOG 9906). A phase I/II study of nedaplatin + 5-FU + RT for T4 disease (JCOG 9908-DI) also has been completed and we will report the results of this study on annual meeting of ASCO in 2003.
A phase II study of Docetaxel for metastatic esophageal cancer, has been completed and showed a response rate of 20.8% using RECIST criteria and 25% by traditional WHO criteria. Docetaxel has modest activity for esophageal cancer and there were no major differences in response rates between RECIST and WHO criteria (ASCO #661). A phase II study of nedaplatin + 5-FU (JCOG9905) as first-line chemotherapy has been finished and a phase II study of nedaplatin + VDS as second-line chemotherapy is underway.
We reported long-term survival and toxicity after definitive CRT for 139 esophageal cancer patients. Median survival time and 5-year survival of 67 patients with potentially resectable stage (T1-3NanyM0) were 44 months and 48%, in 72 patients of unresectable stage (T4/M1a), those were 11 month and 13%, respectively. While definitive CRT showed favorlable survival, late cardiopulmonary toxicities were noted in the longer follow-up(ASCO#573).
2. Gastric Cancer
A phase III study, 5-FU vs CPT-11 + CDDP vs S-1, in advanced gastric cancer patients (JCOG9912) is presently ongoing. A phase III study of 5-FU vs MTX+5-FU against patients with peritoneal dissemination (JCOG0106) has been started. Also, a phase II study of CPT-11+MMC (JCOG0109) as second line chemotherapy against metastatic disease refractory to 5-FU has been started in 2002.
We investigated relationship between biological markers and treatment effects, and reported significance of vascular endothelial growth factor (VEGF) in gastric cancer patients treated with S-1 with/without CDDP. In S-1+CDDP, VEGF(+) patients showed longer survival than VEGF(-) patients (ASCO #606).
3. Colorectal Cancer
We reported the results of pharmacokinetics and pharmacodynamics comparing American and Japanese patients in the phase II study of UFT + oral leucovorine (LV), which is the first bridging study between Japan and the United States. In this study, incidence of grade 3 or higher diarrhea were different among races (Caucasian 9/31> Hispanic 1/4> Oriental 4/44> African-American 0/10) and there seemed to be a racial difference in tolerability of gastrointestinal toxicity(ASCO #330).
A phase II study of oxaliplatin (1-OHP) as second-line chemotherapy has been completed. Subsequently, a phase I/II study of 1-OHP+5-FU+1-LV for chemonaive metastatic colorectal cancer has determined the recommended dose and it has moved to the phase II step. A phase I/II study of the combination of intrahepatic arterial infusion of 5-FU and intravenous CPT-11, a phase II study of Capecitabine as first-line chemotherapy and a phase III study of adjuvant chemotherapy (5-FU/LV vs UFT/LV) after surgery will be started in 2003.
4. Gastric Lymphoma
A multi-institutional prospective study of stomach preserving treatment including eradication of H. pylori, radiation and chemotherapy against localized gastric lymphoma is now underway. Patient accrual to the feasibility study of chemo-radiotherapy for aggressive lymphoma has been completed.
5. Others
A phase II study of STI571 against gastrointestinal stromal tumors (GIST) has been initiated in 2002 and patient accrual has been completed.

A. OHTSU
K. MERA

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