Gastrointestinal Oncology Division

Introduction
The clinical subjects treated in the Gastro-intestinal Oncology Division are cases of early and advanced esophageal cancers as well as cases of gastric and colorectal cancers with distant metastasis. Although chemotherapy for gastrointestinal cancers has been developed, its efficacy in general is insufficient. Therefore, we are trying to investigate and establish new modalities of chemotherapy treatment for these patients

Routine Activities　
The staff of the division consists of five medical oncologists and five residents. All members of our division discuss the treatment for each patient weekly. Inter-group meetings with each surgical division (the Esophageal, Gastric, and Colorectal Surgery Divisions) and the Radiation Oncology Division are held weekly to decide treatment strategies for each individual case or to discuss the future strategy for the disease. Palliative care to improve the physical and psychological aspects of the patients quality of life is another important theme discussed in staff meetings. Anesthesiologists and psycho-oncologists join in and advise us on how to care for the patients during their palliative stage.
In 2001, we treated 1,242 hospitalized patients (663 of whom were newly diagnosed). Of these patients, 188 were entered in protocol studies.

Research Activities
A phase II study was designed to evaluate the efficacy and toxicity of 3 hourly-interval sequential methotrexate (MTX) and 5-fluorouracil (5-FU) with leucovorin (LV) rescue in the treatment of patients with metastatic colorectal cancer. Objective response rate was 36% (15/42). The median survival for all patients was 378 days. The hematological toxicity was mild with no grade 3/4 leukopenia. The major non-hematological toxicity was diarrhea (1 grade 4, 4 grade 3). This treatment is an active regimen in patients with metastatic colorectal cancer. The treatment showed mild toxicity and was fully administered on an out-patient basis (Y. Matsumura).
A phase II study of paclitaxel by three-hour infusion for advanced gastric cancer with short premedication for prophylaxis against paclitaxel-associated hypersensitivity reaction was conducted to determine the antitumor activity and toxicity. Objective response rate was 23% (14/60). Seven of 26 (27%) previously treated patients developed a PR. The study treatment was well tolerated. Paclitaxel is both an active and safe treatment for gastric cancer. Paclitaxel appears to be non-cross resistant to other active agents for gastric cancer (Y. Yamada).

Clinical Trials
We carried out clinical trials in collaboration with the Surgery and Radiation Oncology Divisions at the National Cancer Center Hospital and other institutes..
1. Esophageal Cancer:
A phase II study of the new agent Taxotere against metastatic disease, and a phase I/II study of concurrent low dose FP (low dose 5-FU + low dose CDDP) and radiotherapy against T4 disease finished in 2001. A phase II study of 5-FU plus nedaplatin as a first-line chemotherapy (JCOG 9905), and a phase II study of nedaplatin plus VDS as a second-line chemotherapy against metastatic disease are ongoing. A phase I/II study of concurrent chemotherapy and radiotherapy (5-FU + nedaplatin + radiation (JCOG9908)) against T4 disease, and a phase II study of concurrent chemotherapy (5-FU+CDDP) and radiotherapy against Stage II and III cancers (JCOG 9906) are ongoing. Also, a phase III study of preoperative versus postoperative chemotherapy (5-FU+CDDP) (JCOG 9907) is ongoing.
2 Gastric Cancer:
A phase II study of S1 as second-line chemo-therapy against metastatic disease was completed in 2001. A randomized phase II study of the new agents Iressa, a tyrosine kinase inhibitor of EGF receptor, was also completed in 2001. A phase III study of three arms (5-FU/ CPT-11+CDDP/ S1) has been started in 2000 (JCOG 9912) and is presently ongoing. Also, a phase I/II study of S1+CPT-11 is ongoing. On the basis of results from a phase II study of methotrexate plus 5-FU (JCOG 9603) in patients with malignant ascites, the next phase III study of this combination against peritoneal dissemination (JCOG 0106) will be started in 2002. Also, a phase II study of CPT-11 + MMC as second-line chemotherapy against metastatic disease will be started in 2002.
3. Colorectal Cancer:
A phase I/II study of CPT-11 + 5-FU + Leucovorin is ongoing. On the basis of the results of previous phase I study of Oxaliplatin, a phase II study of Oxaliplatin as second-line chemotherapy is ongoing and a phase I/II study of Oxaliplatin + 5-FU+ Leucovorin as first-line chemotherapy will be started in 2002. A phase I/II study of the combination of intrahepatic arterial infusion of 5-FU and intravenous CPT-11 is planed. Also, a phase III study of adjuvant chemotherapy (5FU/LV vs UFT/LV) after surgery will be started in 2002.
4. Others:
A comparative study in the prevention of CPT-11-induced emesis was completed in 2001. A phase I study of low-dose, protracted infusion of 5-FU plus leucovorin via the central vein using an ambulatory pump against colorectal and gastric cancer is ongoing. Also, a phase I study of the new agent NK-911 (Adriamycinencapsulated polymeric micelle) is ongoing. A phase I study of MCC-465 (Adriamycin-encapsulated liposomes conjugated with monoclonal antibody against a cell surface molecule of gastrointestinal cancers) was completed in 2001. And another phase I study of weekly MCC-465 will be started in 2002. A phase II study of STI571 (inhibitor of the tyrosine kinase activity of c-kit) against gastrointestinal stromal tumors (GIST) will be started in 2002. A pharmacogenomic study regarding some enzymes involved in 5-FU metabolism will be started in 2002.

K. SHIRAO

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