Gastrointestinal
Oncology
Introduction
The Gastrointestinal Oncology Division currently focuses on chemotherapy with or without radiation therapy against gastrointestinal malignancies. We take care of many patients practically, and participate in various clinical studies to develop new or standard treatments prospectively. We also investigate the relationship among clinicopathological features, biological characteristics, and clinical outcomes of each treatment for the purpose of developing treatment-oriented diagnoses, stratification, or individualization of treatment. We are going to validate our strategy in a prospective study.
Routine Activities
We participate in many clinical studies. The number of inpatients we treat has increased yearly, with more than one hundred patients with esophageal cancer treated with chemotherapy (with or without radiation) in 1999. We also identify candidates for outpatient-based chemotherapy, and more than 60 patients receive chemotherapy at the outpatient department every week. The average hospital stay of patients treated with chemotherapy or palliative therapy was as short as 17.8 (median, 11) days. Despite the large number of patients we see, we have had no treatment-related deaths among outpatients. The most appropriate treatment for each patient is determined in case conferences held by the medical, surgical, radiation oncology, and diagnostic radiology staff, and all treatments are initiated with patients・informed consent.
New Developments
1. Esophageal Cancer
We have been performing concurrent chemo-therapy (CDDP + 5-FU) and radiation therapy (FP-R) against both advanced (T4) and resectable (T1-3) esophageal cancer without distant metastasis. We reported on a retrospective comparison between FP-R and surgical resection against resectable (T2-3) esophageal cancer at the annual meeting of the Japan Society for Cancer Therapy in 1999. Thirty-nine patients were treated with FP-R, and 40 received surgical resection in these stages. Although there were more patients with T3 and/or N1 in FP-R than in surgery, FP-R resulted in similar survival rates as surgical resection (4-year survival rates: FP-R 46%, surgery 40%), with better quality of life. A phase II study of FP-R against resectable esophageal cancer will be initiated in the Japan Clinical Oncology Group (JCOG) in 2000. Based on the result of a phase I/II study of nedaplatin + 5-FU against metastatic diseases, a phase I/II study of nedaplatin + 5-FU along with radiation therapy against advanced (T4) esophageal cancer has been initiated. A phase II study of 254-S + VDS against recurrent esophageal cancer after FP-R was started in 1999, and it showed an objective response of 27% (4/15) in the interim analysis. We are also planning a phase II study of Taxotere as treatment against metastatic esophageal cancer.
2. Gastric Cancer
From the
results of a phase III study (JCOG9205) of 5-FU alone vs 5-FU + CDDP vs UFT
+ MMC, 5-FU alone was still recognized as a reference arm against advanced
gastric cancer. A phase III study of 5-FU vs CPT-11 + CDDP vs S-1 in advanced
gastric cancer patients without severe peritoneal dissemi-nation and another
phase III study of 5-FU vs MTX + 5-FU in patients with severe peritoneal dissemi-nation
will be initiated in JCOG in 2000. In retrospective analysis of a combination
chemo-therapy of CPT-11 + CDDP, patients with intestinal type carcinoma showed
longer survival rates than did those with diffuse type carcinoma (MST:intestinal
14 months, diffuse 9 months). In a late phase II study of Taxol, the response
rate was higher than 20% in 60 patients, regardless of prior chemotherapy.
A phase I/II study of CDDP + Taxotere determined the recommended dose at 60mg/m2
of Taxotere and 80mg/m2 of CDDP, and a phase II part is now underway.
We reported that MTX + 5-FU has palliative effects for patients with
DIC and with bowel obstruction by peritoneal dissemination.
We have been investigating the significance and utility of biological markers related to chemo-sensitivity. Vascular endothelial growth factor (VEGF) had an impact on the chemoresponse of CPT-11 + CDDP, and among 55 patients treated with this therapy 25 patients with intestinal type carcinoma who had two or three biological phenotypes out of VEGF (+), p53 (-), and bcl-2 (-) showed remarkably prolonged survival (MST: 545 days). The significance of thymidylate synthase (TS) and dehydropyrimidine dihydrogenase (DPD) in gastric cancer patients treated with S-1 was presented at an ASCO meeting. In patients treated with MTX + 5-FU, 26 patients with Bak (-) survived significantly longer than did those with Bak (+). We are going to confirm these results in the next phase III studies in JCOG.
3. Colorectal Cancer
A phase II study of sequential CPT-11 + 5-FU (JCOG9703) has been completed with a response rate of 45% (18/40). Accrual for a phase I study of oxaliplatin has been completed, and a recommended dose will be determined soon. A phase II study of UFT + oral leucovorine, which is the first bridging study between Japan and the United States, will also be completed soon. In the previous phase II study of S-1 in colorectal cancer, the response rate was 35% (22/62), and another phase II study of S-1 has been initiated. In the patients with metastatic colorectal cancer treated with continuous infusion of low-dose 5-fluorouracil (FU), patients with high TS expression showed a lower response rate than did patients with a low TS expression.
4. Gastric Lymphoma
A multi-institutional prospective study of stomach preservation treatment including eradication of H. pylori, radiation, and chemotherapy against localized gastric lymphoma has been initiated.
|
Average
Hospital Stay (Days) in GI Oncology Division (1994-1999) |
|||||||
|
1994 |
1995 |
1996 |
1997 |
1998 |
1999 |
||
|
All
patients |
35.0 |
36.7 |
23.9 |
17.8 |
15.2 |
16.7 |
|
|
(15) |
(19) |
(10) |
(8) |
(8) |
(9) |
||
|
Chemotherapy
or palliation cases |
44.8 |
44.4 |
28.6 |
19.9 |
16.8 |
17.8 |
|
|
(25) |
(31) |
(16) |
(11) |
(9) |
(11) |
||
|
( ): median (days) |
|||||||
|
Number
of Patients in GI Oncology Divisoin (1994-1999) |
||||||||
|
1994 |
1995 |
1996 |
1997 |
1998 |
1999 |
|||
|
Total
no. of inpatients |
369 |
394 |
625 |
737 |
953 |
1059 |
||
|
No.
of new referrals |
181 |
191 |
259 |
313 |
346 |
360 |
||
|
Endoscopic
Treatment |
50 |
46 |
66 |
102 |
119 |
91 |
||
|
Chemotherapy
cases |
122 |
141 |
191 |
219 |
223 |
269 |
||
|
Esophageal |
31 |
33 |
56 |
79 |
73 |
106 |
||
|
Gastric |
65 |
69 |
78 |
71 |
91 |
77 |
||
|
Colorectal |
26 |
39 |
57 |
69 |
57 |
86 |
||
|
Clinical
Study in GI Oncology Division 1999 |
|||
|
Organ |
Regimen |
Phase |
No. of pts |
|
Esophagus |
Nedaplatin
+ VDS |
II |
5 |
|
Stomach |
Taxol |
II |
8 |
|
CDDP+TXT |
II |
7 |
|
|
CDDP+S1 |
I/II |
4 |
|
|
Colorectal |
CPT-11+5-FU |
II |
13 |
|
UFT-LV |
II |
13 |
|
|
Oxaliplatin |
I |
4 |
|
|
S-1 |
II |
1 |
|
|
Gastric
ML |
non-surgery |
II |
1 |
|
Total |
55 |
||
|
VDS:
vindesin, TXT: decetaxel, LV: leucovorine, ML: malignant lymphoma |
|||
|
Esopaheal
Cancer Treated with Definitive Chemotherapy (1992-1998) |
|||
|
Clinical Stage |
n |
MST(month) |
3-yr survival rate (%) |
|
I |
10 |
not reached |
83 |
|
II |
19 |
not reached |
53 |
|
III |
51 |
14 |
33 |
|
IV* |
35 |
12 |
22 |
|
47
patients with T4 were included
in stage III and IV. |
|||
|
*:
Excluding M1b |
|||
(N. BOKU)
