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A 65-year-old man was referred to our hospital because of weight loss. Endoscopic examination and computed tomography (CT) revealed an advanced gastric cancer with multiple abdominal lymph node swellings. Distal partial gastrectomy was performed but lymph node resection was not done, since it was not thought to be curative. Adjuvant chemotherapy was performed for 4 courses with a regimen of ADM 20 mg/m2 day 1, CDDP 50 mg/m2 day 1, ETP 100 mg/day days 3-7, 5-FU 600 mg/m2 every other day on days 3-29. After 3 courses of ACVF therapy, the patient's serum CEA and SCC level normalized and the lymph node metastases became undetectable by CT scan. No severe side effects were observed at any time during the administration of these medications. In this case, serum SCC level was elevated even though histologic examination did not reveal squamous cell carcinoma but poorly differentiated adenocarcinoma. On immunohistochemical analysis, these tissues were stained diffusely with CEA, locally with AE1 + 3, and partially with PAS or Alcian blue. We speculate that this tumor could have developed the potency of SCC secretions without structural change into squamous metaplasia.

A multicenter co-operative late phase II study of raltitrexed (ZD1694), a specific thymidylate synthase (TS) inhibitor, was conducted in chemotherapy-naive patients with advanced colorectal cancer. Raltitrexed was infused intravenously over 15 minutes once every three weeks. Between April 1996 and September 1998, 61 patients were enrolled and 58 were eligible. Fourteen patients experienced a partial response (PR), 22 no change (NC), 20 progressive disease (PD) and 2 no evaluable (NE). The overall response rate was 24.1% (95% CI: 13.9-37.2%). Responses were seen in lung (22.7%), liver (22.9%) and deep lymph nodes (10.0%). Median survival was 11.6 months. Grade 3 or 4 toxicities were: leukopenia (13.8%), neutropenia (24.1%), hemoglobin decrease (15.5%), FBC decrease (6.9%), hematocrit decrease (6.9%), thrombocytopenia (6.9%), transient SGPT increase (6.9%), nausea/vomiting (20.7%), anorexia (15.5%), and asthenia (6.9%). These adverse reactions were considered to be manageable. Only one death was associated with drug treatment. These results suggest that raltitrexed provides an effective and convenient treatment for patients with advanced and previously untreated colorectal cancer.

For patients with unresectable gastric cancer registered between July 1994 and September 1995, the following dosage regimen was examined: a drip infusion of cisplatin (CDDP) at 7 mg/m2/day for 5 consecutive days and 2-day withdrawal a week for 3 weeks with concomitant sustained drip infusion of 5-FU at 300 mg/m2/day for 21 days. The whole cycle was repeated again after 2-week withdrawal. The antitumor effect was seen in 39.4% among 33 cases. With respect to histological classification, there was no difference in appearance of the effect between the moderately differentiated type at 62.5% and the low-differentiated type at 42.9%. The cases which became resectable after the administration included those in which the tumor disappeared completely in the resected specimens. As adverse reactions encountered in the cases above Grade 3, anorexia, nausea and vomiting and diarrhea were seen as clinical symptoms in 10, 5.3 and 11.8%, respectively. As laboratory test values, decrease in hemoglobin, leukocytopenia and thrombocytopenia were seen in 16.7, 15.8 and 5%, respectively, while renal or liver dysfunction did not occur. This dosage regimen was considered useful for unresectable advanced gastric cancer, although myelosuppression should be watched carefully.

Three patients with chemotherapeutically pretreated metastatic gastric cancer were given MAC-VD therapy combining MMC, ADM, CDDP, Etoposide (VP-16) and 5'-DFUR. All were evaluable for their responses. Patients ranged in age from 49 to 61 years. Performance status scale (P.S.) grade 0 was two cases; and P.S. grade 1 was one case. The overall response rate, CR+PR, was 0+2/3 (66.7%). The response rate in the primary lesions was 0%, against 66.7% (2/3) in the liver, 100% (1/1) in the spleen, 100% (1/1) in the lung, and 0% in the abdominal lymph node metastasis. The chief manifestations of toxicity were hematologic, such as leukocytopenia, anemia and thrombocytopenia in 100% of the cases. Non-hematologic toxicity was seen in alopecia in 66.7%, diarrhea in 33.3%, fever in 33.3%, and pigmentation in 33.3%. Severe toxicity was not observed. From these data, the administration of MAC-VD therapy was considered tolerable and these data suggested that this therapy could be given as a second-line chemotherapy when initial treatment failed to obtain a response after a partial response.

We organized a cooperative research group consisting of 10 institutions and UFTPM therapy was given patients with unresectable and postoperatively relapsed stomach cancer. As the result, 20 cases were registered and the ratio of PR according to the criteria of stomach cancer chemotherapy was 4 out of 17 complete cases (23.5%), excluding 3 incomplete cases. The efficacy for the cases treated with more than 2 courses was 36.4% (4/11) and that for cases with 3 courses was 75% (3/4). One case with 3 courses was resectable and the cancer cells disappeared. Adverse effects of grade 3 or more according to the WHO criteria were observed in 20% of the cases.

A co-study was conducted on treatment with high dose 5'DFUR+MMC in order to determine its effectiveness as a systemic chemotherapy in patients with advanced and recurrent colorectal cancers. The treatment schedule included 5'-DFUR given orally at a dose of 1,600 mg/body/day for five consecutive days, a two-day discontinuation, then repeated medication with the above, and MMC injected intravenously at a dose of 6 mg/m2 once every four weeks. One course consisted of four weeks, and courses were repeated as long as tolerated by the patients. Twenty-nine patients were registered for the study and 28 cases were perfectly capable of anti-tumor responses. The response rate was 25.5%, including: CR, 2; PR, 5; NC, 11; and PD, 10 cases. Responding cases were found in metastases to the lung, cervical lymph node and abdominal wall. Response rate was especially high in pulmonary metastases at 41.7% (5/12 cases). The slight side effects were mostly gastrointestinal in nature and did not necessitate drug discontinuance. The results suggest that treatment with high dose 5'-DFUR+MMC is useful for advanced and recurrent colorectal cancers, especially those with pulmonary metastases.

Outpatients with advanced and recurrent breast cancer were treated by a combination therapy of the following drugs: doxifluridine (5'-DFUR) orally administered at a dose of 1200 mg/day; cyclophosphamide (CPA) orally given at dose of 100 mg/day; and tamoxifen (TAM) orally given at dose of 20 mg daily. 5'-DFUR and CPA were administered on consecutive days 1-14, then discontinued for 14 days. The response rate was 44.8% including five CR and eight PR out of 29 complete cases. As for response cases in terms of the subject lesions, corresponding cases were chiefly found in soft tissue and the lung. As for the response rate with or without pretreatment, cases previously treated showed a higher response rate such as 42.9% indicating that the present therapy was effective in pretreatment cases. The main side effect was leukopenia, but not so severe. Few cases with diarrhea were found. Based on the above findings, the present treatment is conceivably a highly useful therapy, on an outpatient basis, for advanced and recurrent breast cancer, especially metastatic lesions of soft tissue and the lung.

We studied the endoscopic features in 6 cases of advanced gastric cancer responded to chemotherapy. Patient characteristics were as follows. [table; see text] Age 43-77 (mean 63 years old) Endoscopic type Mean duration of PR was 26.6 weeks. The process of the improvement of primary lesion as judged by endoscopic findings were as follows. Firstly getting flat of wall, secondly reduction in size of ulcer, and lastly changing into scar. Number of reported cases including our case No. 6 which are diagnosed as scar endoscopically after chemotherapy and are operated successfully has been increasing. Most of them showed scar macroscopically with wide and irregular surface. Especially our case No. 6 showed keloidal scar. In these cases, the histological improvement into grade 2-3 was observed in scared tissue. Sooner or later, such a process of endoscopic improvement was observed 4-8 weeks after initiation of chemotherapy. Unless the endoscopic improvement was observed 8 weeks after initiation, regimen of chemotherapy should be changed into others.

Twenty-five patients with advanced gastric cancer were treated with a combination chemotherapy. The levels of serum CEA, CA 19-9, TPA and CA 125 were measured before and during chemotherapy (4 and 8 weeks). One complete and 10 partial responses were obtained, and the response rate was 44%. Pretreatment positive rates of these four tumor markers were all more than 60%, and the positive rate of combination assay was 96%. The mean percent changes of these four tumor markers were similar and correlated well with the response to chemotherapy. There was a significant correlation between tumor reduction and decrease of serum CEA in the responders with measurable lesions. These results suggest that the measurement of changes of serum tumor markers may be useful for monitoring the response to chemotherapy in patients with gastric cancer. It also may be useful to determine early the effectiveness of the treatment.

Eighteen patients with progressive/locally recurrent cancer of the stomach were given therapy with MMC, ADM, CDDP, Etoposide (VP-16), and 5'DFUR (MAC-VD therapy). Drugs were administered intravenously with MMC 10 mg/m2, ADM 20 mg/m2, and CDDP 50 mg/m2 on day 1; orally with etoposide 100 mg/day for five consecutive days from day 3; and orally with 5'DFUR 600 mg/day for three weeks from day 3 followed by discontinuation for one subsequent week. This drug regimen was one course of the treatment and repeated as far as possible. There were 16 evaluable cases; the sex distribution was ten males and six females. Patients ranged in age from 43 to 78 years. P.S. 1 was two cases; 2 ten cases; and 3 four cases. The overall response rate, CR + PR, was 1 + 7/16 (50%), while this rate for primary disease was 2 + 5/16 (43.8%). Of the two CR cases, one primary lesion became operable and CR was demonstrated histologically. The overall response rates, CR + PR, for metastatic lesions were 1 + 3/9 (44.4%) for the liver; 0 + 1/4 (25.0%) for the abdominal lymph nodes; 0 + 1/2 (50.0%) for the superficial lymph nodes; 0 + 1/2 (50.0%) for the bones; and 0 + 1/1 (100%) for the lung. The median duration of the response was 3.7 months (range between 1.5 and 8.2+) and the median duration of survival 5.1+ months (range between 2.2+ and 13.3+). At the same time, the hematological side effects of both leukocytopenia and hypohemoglobinemia were seen in 43.8% of the cases. Non-hematological side effects included alopecia in 18.8% and nausea/vomiting in 12.5%. There was no case of discontinuation due to side effects. It was concluded that the therapy with MMC, ADM, CDDP, etoposide and 5'DFUR (MAC-VD therapy) proved to be a very promising drug regimen in the treatment of stomach cancer with high rates of response and is expected to be a step forward in the establishment of interdisciplinary treatment.

Unlabelled: An SF-SP Tegafur spansule preparation was administered to 26 patients with advanced cancer (24 evaluable), and the clinical effectiveness and toxicity were studied. In most of cases, daily dosages of 800 mg were administered in two parts, in a few cases, daily dosages of 1,000 mg or 1,200 mg were given. Clinical effectiveness: The evaluation of effectiveness was based on the Koyama-Saito group criteria. Of the 24 evaluable cases, PR was observed in 3 cases of gastric cancer, one of colon cancer, and one of liver cancer, a total of 5 cases (20.8%). In these 5 cases the daily dosage was 800 mg, and the median duration of PR was 51 days., Toxicity: TOXICITY was observed in 3 (11.5%) of the 26 cases.

Discussed is a 62-year-old male who was admitted to hospital for an examination of the stomach. Physical examination and associated laboratory data uncovered no unusual results. On barium ingestion, however, an X-ray revealed an oval shaped filling defect at the greater curvature of the antrum. Further, endoscopic examination revealed half of a globular tumor with a surface redness and bridging folds radiating from the tumor. Examination of a biopsied specimen led to the determination of a glomus tumor and the patient underwent an operation. On operation, a well circumscribed submucosal tumor, 1.5 x 1.5 x 1.5 cm in size, with lobulation was found in the antral submucosal region, this tumor extending to the subserosa. A histopathological study of this neoplasm revealed that it consisted of irregular, swollen, blood vessel lumens lined with flattened endothelial cells, with surrounding aggregates of glomus cells forming lobules. In addition to this case, 52 cases of glomus tumors reported in the Japanese literature are discussed.

5'-DFUR was administered orally to advanced or recurrent cancer patients at a daily dosage of 600-1200 mg divided into 3 or 4 times a day. Out of 13 evaluable cases 2PR, 2MR, 4NC and 5PD were observed, response rate was 15.4%. PR were obtained in one gastric cancer case and one breast cancer case. Side effects were observed in 6 cases out of 14 cases (42.9%) and major adverse reaction was gastro-intestinal toxicities such as anorexia, nausea-vomiting and diarrhea. Two leukocytopenia and one erythrocytopenia were observed. This study indicated that 5'-DFUR would be useful as a new anticancer agent.

Since June 1984, 23 cases of progressive or recurrent breast cancers were treated with combination chemotherapy of VAM-UFT consisting of vincristine, adriamycin, mitomycin C and UFT. Clinical effects of VAM-UFT therapy were 3 CR, 12 PR, and the response rate was 65.2%. Its effective interval was 3 months. But the patients treated with over 4 cycles of VAM-UFT therapy showed an 85% response rate, with a 5-month effective interval. In each patient's background, a shorter disease free interval tended to be more highly effective, but other factors were not significant. Scirrhous carcinoma of pathology evidenced slightly high response rate. Compared with the survival time of patients treated with under 3 cycles and over 4 cycles of this therapy, the latter was significantly longer. Toxicity involved leukocytopenia (74%), thrombocytopenia (22%), anemia (30%), alopecia (91%), nausea and vomiting (87%) and stomatitis (35%), but cases in which the treatment was stopped were not observed. Therefore VAM-UFT therapy had a highly therapeutic effect, reflected in an 85% response rate, for progressive or recurrent breast cancers.