Twenty-five patients with metastatic breast cancer who had failed with combination chemotherapies including adriamycin were treated with a combination of mitomycin C, methotrexate, and vincristine (MMV). MMC 5 mg/m2, methotrexate 18 mg/m2, vincristine 0.7 mg/m2 were given i.v. on days 1 and 8, and repeated every 21 days. Seven patients (28%) experienced a partial response: 7 maintained NC and 11 failed to respond (PD). Median duration of regression was 12 weeks. Median survival time in PR patients was one year and 3 months, contrary to 6 months in patients with NC or PD. This combination was well tolerated except thrombocytopenia in 5 patients.

Among 56 patients with stomach cancer preoperative cell-mediated immunity in relation to clinical staging was studied: eight cases were subjected to a control study in order to evaluate effects of PSK on cell-mediated immune status, preoperatively and postoperatively at 1, 3, 6, 9 and 12 months. They were given MMC and FT-207, and 4 of them (the study group) received PSK in addition. Preoperative study showed that WBC count, peripheral lymphocyte and T-lymphocyte tended to show a decrease as the disease progressed, whereas there was no major change in PHA response of lymphocytes. Postoperative study on 4 control patients showed that peripheral lymphocyte and T lymphocyte decreased, and that IgG X FcR+ T cells significantly increased during postoperative period. Four patients in the study group who received PSK, however, did not show these characteristics. It thus appears that PSK is effective in activating cell, while immunity during postoperative period, possibly by counterworking suppressor cells including IgG X FcR+T cells.

Since 1976, postoperative long term immunochemotherapy (PLIC) with PSK and 5-FU Dry Syrup (5-FUDS) was performed after tumor resection in gastric and colorectal cancer patients. Successful continuation over one year of the therapy was done in 40 cases at stages III and IV (+V) in the period between January 1976 and April 1979. These cases were analyzed and following results were obtained. Two-and 3-year survival rates were 80% and 65% respectively when the total cases of one year survival was taken as 100%. However, there were recurrent or tumor-bearing patients being treated by PLIC and, if they had died within the respective years, 2-and 3-year survival rates would have been reduced to 67.5% and 32.5%, respectively. These survival rates were roughly similar as those of historical control group, in which no immuno-chemotherapy was done. Characteristic features of non-specific immunological parameters seen in the recurrent or tumor-bearing cases of relatively good clinical course were improvement in T cell percentage, reduction or stop of in IgG-FcR (+) T cell percentage and maintenance of a good nutritional condition.

In clinical practice, a number of tests are conducted to determine the immune reactivity of the patients. The principal cell in immunological surveillance against cancer has been thought to be the T cell. However, multiple immunological methods to evaluate the T cell function have failed to confirm a major role for the T cell in immunological surveillance. The role of other potential effector cells such as NK cells, K cells, macrophages and granulocytes needs more intensive investigation. In this report the effects of anticancer agents on immune effector cells were analyzed and the possibility about the development of a reliable monitoring procedure for determining a potent treatment protocol was discussed.

The long-term therapeutic results in patients with glioblastoma multiforme and malignant astrocytoma were compared between 15 cases of levamisole treated group and 18 cases of control group similar in method and time of treatment to the levamisole treated group. As the result, it was found that the prolongation of life was noted in the levamisole treated group compared with the control. In adult patients, the levamisole treated group survived significantly longer than the control group (p less than 0.05). There is, however, no significant difference of prolongation of the survival time between the levamisole treated (8 cases) and control (8 cases) groups, both which were pretreated by chemoradiotherapy using ACNU and vincristine. This paper refers also to side effects of levamisole.

A neo-adjuvant chemotherapy as a preoperative and preradiation chemotherapy was studied in 60 cases of the head and neck cancers. Out of 60, 29 cases were treated with peplomycin (PEP) and 31 with combination chemotherapies which include vincristine (VCR), methotrexate (MTX), bleomycin (BLM), mitomycin C (MMC); VCR, MTX, BLM (Mathé); VCR, MTX, BLM, 5-FU, hydrocortisone (Price-Hill A); hydoxyurea, adriamycin, BLM; VCR, MTX, PEP; cisplatin (CPDD), PEP. In the group treated with PEP, CR was achieved in one case and PR in 14 cases with a response rate of 52%. Five-year survival by Kaplan-Meier's method after all treatment was 34%. In the group treated with combination chemotherapy, CR was achieved in 5 cases and PR in 19 cases with a response rate of 77%. Three-year survival of this group was 82%. Responders to PEP as well as combination chemotherapy were more often rendered disease-free after all treatment than non-responders. We concluded that two courses of VMP therapy (VCR, MTX, PEP) would be appropriate for the outpatients with advanced stage I or stage II, meanwhile two courses of CP therapy (CPDD, PEP) was inpatients with stage III or stage IV as a neo-adjuvant chemotherapy.

The effect of peplomycin by three different treatment schedules was studied in mice bearing Ehrlich Effeit of carcinoma. continuous i.p. infusion of peplomycin via an osmotic minipump was compared to those by intermittent injection and daily injection. Equivalent total doses of the drug were administered in all three schedules. Continuous infusion for 7 days produced marked inhibition of tumor growth, which was significantly better than intermittent injection or daily injection of the same total dose. The effect of bleomycin by continuous infusion was significantly better than that by intermittent injection, but was as equally effective was daily injection. The results indicate that the continuous infusion of peplomycin is a useful treatment method.

Retinol-type vitamin A enhances cytocidal effect of several anticancer agents or radiation in in vitro as well as in vivo. We describe therapeutic effect fo a combination therapy of vitamin A and other agents which has been applied to cancer patients since 1972. We also discuss a possible role of vitamin A in the efficient synergistic effect.

Bestatin is a low toxic peptide discovered by Umezawa et al. and animal experiments have revealed that Bestatin enhances the immune response to activate the defense mechanism of the living organism, and thus suppresses the growth and metastasis of cancer. Recently we performed a phase I study of Bestatin to determine an optimal dose. Analysis of changes in immunological parameters at all the tested dosages of Bestatin led to the presumption that its optimal dose was in the low dosage ranging from 10 to 100 mg daily. Because the effects of a single administration of Bestatin on immunological parameters disappeared at day 7, 2 or 3 times administration per week or even daily seemed to be required. Hematology, hepatic and renal function tests revealed no apparent adverse reactions which were considered to be derived from Bestatin administration.

Twenty-one patients with hematopoietic malignancies including 6 previously untreated, 9 pretreated, and in relapse, 5 in complete remission and one in partial remission all were treated with PL-AC. The patients consisted of 12 acute myelocytic leukemias, 4 acute monocytic leukemias, 2 acute lymphocytic leukemias, one erythroleukemia, one malignant lymphoma and one chronic monocytic leukemia. PL-AC was given orally at a dosage of 50-1200 mg daily. Mean total dosage was 4.74 g (0.6-15.25), and the mean administration period was 3.43 days (1-122). days Responses were observed in 4 out of 9 pretreated patients by a decrease of blast cells in the peripheral blood. Partial remission was obtained in one case which lasted 8 months. Out of 5 previously untreated acute leukemias, one partial remission and 4 hematological responses were observed. The plasma concentration of Ara-C was maximal at 3 hours and was not detectable after 12 hours. Side effects observed were nausea in 5 patients vomiting in one patient and liver dysfunction in one patient. These side effects however were not so severe as to stop drug administration. PL-AC may be administered in doses ranged 150-250 mg for 2-3 weeks without any severe side effects, and with some clinical effects.

Anticancer agents, Mitomycin C and Adriamycin, were immobilized on absorbable gelatin materials, respectively with a blood clotting factor, Factor XIII and thrombin with a special technique we have developed. The materials were clinically applied as thrombotic agent in pre-operative therapeutic transcatheter arterial embolization (TAE) to 5 patients with locally advanced breast cancer. About 1 week after TAE, the regression of the primary tumor was found in 4 out of 5 patients; all patients received currative operation without any trouble. The histological examinations of the excised specimens showed remarkable degenerative changes (IIA and IIB: Shimosato's classification) of cancer cells not only in the primary tumor, but also in the metastatic regional lymph node. No complications due to the TAE were observed. These findings strongly suggest that this newly deviced materials are quite effective in pre-operative treatment for the locally advanced breast cancers.

The effectiveness of postoperative adjuvant chemotherapy on aged patients (more than 70 years old) with resectable gastric carcinoma was examined in our Department. Of the 178 patients, 75 patients received the drugs on various regimen and 103 patients had no chemotherapy a control group). No significant difference was noted in patient characteristics of age, sex and curability. In advanced gastric carcinoma such as stage III and IV, a significant increase in long-term survival after surgery was obtained with combination chemotherapy or immunochemotherapy compared with the control group (P less than 0.05). On the other hand, there was no significant difference in a survival rate of the patients with stage I and II.

The effect of post-operative adjuvant chemotherapy on the prognosis of gastric cancer patients with hepatic metastases was evaluated. Forty-two cases were classified into-following four groups: (A) no chemotherapy, (B) short-term chemotherapy (5 g of 5 FU i.v., or 1/2 FM (F') C alone), (C) long-term chemotherapy (1/2 MF (F') C plus 0.6 g of FT-207 per os), (D) long-term chemotherapy (1/2 MF (F') C plus 1.5 g/day of FT-207 per annum). Six, nine, twelve month survival rates of patients in group (D) was significantly higher than group (A). Mean survival time of each group was: (A) 4.7, (B) 5.2, (C) 5.7 and (D) 9.1 months. Correlation between the survival time and the total dose of FT-207 was observed. Total dose of FT-207 in group (D) was 129.3 g and 60.8 g in group (C). These may reflect the results that the rectal administration was more effective than the oral administration of FT-207.

In order to evaluate clinical efficacy of Lentinan (LNT), a purified polysaccharide extracted from Lentinus edodes, randomized controlled studies with envelope method have been conducted on the patients with advanced or recurrent, stomach, colo-rectal and breast cancer. Administration condition of LNT for gastrointestinal cancer was designed as the following: LNT was administered intravenously at doses of 1 mg/person/day twice a week or 2 mg/person/day once a week in combination with mitomycine C + 5-FU (MF) or tegafur (FT). Control therapy was the administration of MF or FT alone. Survival curve drawn by Kaplan-Meier's method showed that life span prolongation effect of LNT was observed with statistical significance (P less than 0.05 or P less than 0.01) by use of generalized Wilcoxon's test. Moreover, improvement of host immune responses was observed in LNT treated group, and hematological survey showed that incidence rate of abnormal value was significantly low in LNT treated group. Thus, LNT should be effective for the patients with advanced or recurrent stomach or colo-rectal cancer in combination with chemotherapeutic agents such as MF or FT. Regarding advanced or recurrent breast cancer, study is underway. LNT has been administered as an agent for supportive therapy to the patients with complete response, partial response or stable diseases which were induced by prior surgery of oophorectomy. Again, life span prolongation effect of LNT has been observed with statistical significance (P less than 0.05). This result suggests that LNT would also be effective for the patients with advanced or recurrent breast cancer as an agent for supportive therapy.

The first interim analysis on the results of a randomized controlled trial with or without Levamisole in combination with chemotherapy as an adjunct to surgery for gastric cancer was reported. The study was performed by the cooperation of 21 major hospitals in Japan. Two protocols were investigated. In Protocol A, the efficacy of combining Levamisole with Tegafur was tested and in Protocol B, Levamisole with 5-Fluorouracil. In Protocol A, the combination of Levamisole with Tegafur indicated significant elevation of survival rate in rather advanced patients such as stages III and IV or ps (+), n (+) cases. On the other hand, in Protocol B, no difference was observed between Levamisole (+) group and the control.