Table of Contents
Routine Activities
The staff provide both outpatient- and inpatient services, including chemotherapy and endoscopic examination and treatment for gastrointestinal malignancies. Various case conferences on gastrointestinal malignancies are held every evening. The number of new referrals with esophageal and colorectal cancer has shown a remarkable annual increase, while that of gastric cancer has been stable. In 1996, inpatient chemotherapy was moved to the outpatient department or short term admission-based in as many cases as possible. Thus, in 1997, the period of each admission was dramatically shortened to an average of 18 days for all inpatients and 20 days for those given chemotherapy or palliative therapy. We are also exploring the clinical application of recently developed molecular research on endoscopic biopsy materials. These techniques are used to study the biological behavior of the tumors with the future aim of individualized treatment.
New Developments
A phase II trial of concurrent chemotherapy (5FU+CDDP) and radiotherapy with prophylactic G-CSF support for T4/M1 LYM esophageal cancer was completed, with a CR rate of 37% (13/35). An analysis of the 50 patients enrolled in this study and the previous pilot study without G-CSF revealed a CR rate of 34% (17/50) and a response rate of 86% (43/50), with one- and three-year survivals of 43% and 22%, respectively. In a multivariate analysis of survival including clinical background and immunohistochemical staining of 5 markers associated with chemosensitivity in pretreatment biopsy specimens, non-T4 was the best prognostic factor, followed by macroscopic type (type 2) and p53 positivity.
Another 39 patients with T1-3/N0-1 diseases given chemoradiation therapy because of complications or refusal of surgery were added to the retrospective analysis of response and survival. In a total of 89 patients given chemoradiotherapy, there were 7 T1, 4 T2, 46 T3 and 32 T4 diseases, and 7, 10, 39 and 33 in UICC clinical stages I, IIA, III and IV, respectively. CR rates according to T factors were 100%, 65%, and 31% for T1-2, T3 and T4, respectively. Three treatment-related deaths (3%) occurred during the study period. With a median follow-up period of 28 months, overall three-year survivals according to T-factors were, 77, 100, 51, and 12% for T1-4 diseases, respectively. These survivals were apparently comparable to those of radical surgery in Japan. We are now conducting a prospective multi-institutional phase II study of definitive chemoradiation therapy for stage II-III carcinoma of the esophagus.
A randomized phase III trial of the Japan Clinical Oncology Group (JCOG), comparing 5FU alone with UFT+MMC and 5FU+CDDP for metastatic gastric cancer, was completed this year. The final result will be reported in 1998. Some promising results were obtained in the late phase II trials. S-1, a new oral fluoropyrimidine, showed excellent activity with a response rate of 49% and a combination of CDDP and CPT-11 resulted in a response rate of 58% for chemotherapy-na•ve patients, with a few CR cases of both being included. These treatments will be evaluated in a future phase III trial. Numerous attempts to predict chemosensitivity and patient survival have been performed using biopsy materials. In gastric carcinoma treated with 5FU+CDDP, overexpression of vascular endothelial growth factor (VEGF) predicts a significantly better response, as confirmed in patients enrolled in the CDDP+CPT-11 trial. These approaches will be reconfirmed using biopsy materials from patients registered in the above phase III trials in 1998.
For gastric lymphoma, a retrospective analysis of 54 cases was completed this year. Based on the results, a prospective non-surgical approach consisting of eradication, irradiation and chemotherapy has been initiated according to clinical stage and histologic classification.
A total of 95 chemotherapy-na•ve colorectal carcinoma patients treated with chemotherapy was analyzed retrospectively. The overall response rate was 22 % and median survival of the 95 with metastatic disease was 10 months. These data will serve as controls for ongoing and future biologically-based strategies.
Statistics
| 1994 | 1995 | 1996 | 1997 | |
| Total no. of inpatients | 369 | 394 | 625 | 737 |
| No. of new referrals | 181 | 191 | 259 | 313 |
| EMR* cases | 50 | 46 | 66 | 102 |
| Chemotherapy cases | 122 | 141 | 191 | 219 |
| Esophageal | 31 | 33 | 56 | 79 |
| Gastric | 65 | 69 | 78 | 71 |
| Colorectal | 26 | 39 | 57 | 69 |
| 1994 | 1995 | 1996 | 1997 | |
| All inpatients | 35.0 (15) | 36.7 (19) | 23.9 (10) | 17.8 (8) |
| Chemotherapy or palliaton cases | 44.8 (25) | 44.4 (31) | 28.6 (16) | 19.9 (11) |
| T stage | No. of pts. | CR rate (%) | 3-yr survivl (%) | |
| Cause specific | Overall | |||
| T1 | 7 | 100 | 100 | 77 |
| T2 | 4 | 100 | 100 | 100 |
| T3 | 46 | 65 | 56 | 51 |
| T4 | 32 | 31 | 13 | 12 |
( A. Ohtsu)