Gastrointestinal Oncology
Introduction
The Gastrointestinal Oncology Division participate in various clinical studies to develop new or standard treatments, and investigate the relationship among clinicopathological features, biological characteristics and clinical outcomes for developing treatment-oriented diagnosis, stratification or individualization.
Routine Activities
We perform short term admission based or outpatient based chemotherapy, and in some patients chemotherapy is initiated at the outpatient department. Thus, more than 60 patients receive chemotherapy at the infusion center every week, and the average hospital stay was 16.8 (median, 9) days.
The treatment for all patients is discussed in conferences consisting of surgeons, diagnostic radiologists, and radiation oncologists, and is initiated with the patients' informed consent. For example, when a patient with esophageal cancer is diagnosed to be in an operable stage, information on surgical resection and chemoradiation therapy is explained by the surgeons and by us separately, and a treatment is decided by the patient. In 1998, 24 of 46 (52%) patients with resectable esophageal cancer received chemoradiation therapy and 22 (48%) underwent surgical resection.
New Developments
1. Esophageal Cancer
Against no-organ metastatic esophageal cancer, concurrent chemotherapy (CDDP+5-FU) and radiation therapy (FP-R) are performed. The validity of our criteria of anti-tumor effects (CR) against primary lesions and lymph node metastasis was confirmed. Malignant fistula to bronchus and/or mediastinum were closed in 17 of 24 (71%) patients after FP-R. As late adverse reactions, pleural and pericardiac effusion were observed in 8 (11%) and 7 (10%) of 71 patients after FP-R. The 3-year survival rates of the patients with T1-2, T3, T4 esophageal cancer were 91% (n=11), 49% (n=44), and 14% (n=35). these results of fp-r against operable esophageal cancer appeared to be comparable to those of surgical resection. we are planning a phase ii study of fp-r against operable esophageal cancer in Japan Clinical Oncology Group (JCOG). In the pilot study of nedaplatin (254-S)+VDS against recurrent esophageal cancer after FP-R, the response rate in the metastatic measurable lesions was 40% (6/15), and we are planning a phase II study. Phase I/II study of 254S+5-FU against metastatic or recurrent esophageal cancer was completed and a phase II study will be initiated in JCOG.
2. Gastric Cancer
The results of the phase III study (JCOG9205), 5-FU alone (FU) vs 5-FU+CDDP (FP) vs UFT+MMC (UFTM), against advanced gastric cancer were analyzed in 1998, which showed no survival benefit for FP and UFTM compared to FU. In the phase II study of CPT-11+CDDP, the response rate was 59% (17/29) and the median survival time (MST) was 322 days. In the two phase II studies of S-1, the response rates were 49% (25/51) and 40% (20/50), and MSTs were 250 and 207 days. We have treated gastric cancer patients having measurable metastatic lesions with CPT-11+CDDP and those having peritoneal dissemination with MTX+5-FU, which resulted in MSTs of 383 days and 298 days, respectively. From these results, we are planning two phase III studies in JCOG, FU vs MTX-5-FU, and FU vs CPT-11+CDDP vs S-1, in advanced gastric cancer patients with and without severe peritoneal dissemination, respectively. We validated the significance of biological markers, among the patients enrolled in the phase III study (JCOG9205). Vascular endothelical growth factor (VEGF) might be useful for selecting the chemotherapy regimen, FP or FU. VEGF was also implicated to antitumor effects of CPT-11+CDDP. In the early phase II study of taxol, the response rate was 20% in 15 patients, and a late phase II study is ongoing. A phase I/II study of CDDP+taxotere is now underway.
3. Colorectal Cancer
In the phase II of S-1 against colorectal cancer the response rate was 35% (22/62) and MST was 12 months. A phase II study of sequential CPT-11+5-FU at the recommended dose and schedule by our previous phase I/II study is ongoing. A phase I/II study of UFT+oral leucovorine, which is the first bridging study between the United States and Japan, has been initiated. Among the patients with poorly differentiated adenocarcinoma, responders survived longer than non-responders, whereas there was no difference in survival between the two with evidence that all seven 2-year survivors were non-responders among well or moderately differentiated adenocarcinomas. We are investigating the relation between antitumor effects, survival, and biological markers in respect to chemosensitivity and cell cycle regulation.
4. Gastric Lymphoma
We are planning a prospective study of stomach preserving treatment including eradication of H. pylori, radiation and chemotherapy against localized gastric lymphoma. In 1998, a retrospective study was done to standardize the diagnostic criteria in histology of MALT lymphoma and to consider the new protocol. This study will be initiated in 1999.
Statistics
| 1994 | 1995 | 1996 | 1997 | 1998 | |
| Total no. of inpatients | 369 | 394 | 625 | 737 | 953 |
| No. of new referrals | 181 | 191 | 259 | 313 | 346 |
| EMR cases | 50 | 46 | 66 | 102 | 119 |
| Chemotherapy cases | 122 | 141 | 191 | 219 | 223 |
| Esophageal | 31 | 33 | 56 | 79 | 73 |
| Gastric | 65 | 69 | 78 | 71 | 91 |
| Colorectal | 26 | 39 | 57 | 69 | 57 |
| 1994 | 1995 | 1996 | 1997 | 1998 | |
| All patients | 35.0 (15) | 36.7 (19) | 23.9 (10) | 17.8 (8) | 15.2 (8) |
| Chemotherapy or palliation cases | 44.8 (25) | 44.4 (31) | 28.6 (16) | 19.9 (11) | 16.8 (9) |
| Clinical stage | n | CR rate (%) | MST (month) |
| T1,2 | 11 | 100 | 44 |
| T3 | 44 | 68 | 30 |
| T4 | 35 | 26 | 8 |
| Treatment | n | Response rate | MST (month) |
| CPT-11+CDDP* | 40 | 50 | 13 |
| MTX+5FU** | 46 | 45*** | 10 |
*For patients with measurable metastatic lesions.
**For patients with peritoneal dissemination.
***In 31 patients having measurable or evaluable lesions.
(N. Boku)
