From the results of the 1st and 2nd screening as to the antitumor effect of organosilica compounds, two compounds, namely, SDK-50 (2-piperidinoethyl-phenyldimethyl-silane) and SDK-47 (3-N-2-propenylamino) propyltrimethyl-silane were selected. These two compounds were further tested by using the solid form cancer of Ehrlich, sarcoma-180 and Lewis lung carcinoma in mice and moreover the rats bearing ascites hepatomas. AH-13, 130, 272, 44, 66F, 66, 7974, 41-C, 60-C and 109A. From the summarized data, it may be said that the effect of SDK-50 is relatively superior to SDK-47. In addition of the inhibitory effect on cancer cells, it was found that SDK-50 possesses an activating effect of delayed type hypersensitivity. This effect of SDK-50 was equivalent to PSK or SPG.

Experimental chemotherapy has been studying with choriocarcinoma in nude mice transplanted from drug resistant patients. The following results: 1) the combined therapy with MTX and ACD was not always effective and in place of one of them, the combination of CPM was effective 2) addition of VCR was effective; were obtained. These results were applied to two patients in clinic. 1) The first patient failed to obtain complete remission by the course of ACD, MTX + ACD, and MTX + ACD + CPM (MAC) therapy. Then the combination therapy with ACD + CPM made her HCG titer regressed to negative immediately. She is free from disease now. 2) The HCG titer and pulmonary metastasis of the second patient showed resistance to MAC therapy, CHAMOMA therapy, and the combined therapy with MTX. The combination chemotherapy with ACD + CPM + VCR made her HCG titer become to regressed and the pulmonary metastasis reduce to 1/4 in size. The clinical application of the results from experimental chemotherapy was defined to be possible. The experimental model will contribute to establish the schedule of the rational chemotherapy for drug-resistant choriocarcinoma.

Therapeutic effect of p-aminobenzoic acid-N-xyloside Na (K-247) were studied. Eleven patients with a variety of solid tumors were treated with K-247 alone. K-247 was given orally 800mg daily for 4 weeks. As for side effect of the drug, only mild gastritis was observed in a few patients. Partial response (over 25% reduction of tumor size) with a median duration of two months was observed in 3 patients. These cases were metastatic tumor of lung from the carcinoma of thyroid, metastatic tumors of lung from the carcinoma of kidney, and mediastinal tumor. In eight patients the response was classified as no change and in one patient there was progressive disease. Thus K-247 has some therapeutic activity in patients with solid tumor. Combination therapy of irradiation and administration of K-247 were also studied. In twelve patients received the combination therapy, partial response was observed in 7 patients with complete response in 3 patients. In some patients it seems that the effect of irradiation was enhanced by K-247 administration. To confirm this observation, randomized controlled trial is required.

Five patients with malignant pleural effusion were treated with intrapleural administration of ACNU. Three of 5 patients showed cytologically negative in the pleural fluid and the fluid was eliminated in two patients. In 5 patients, 200 mg of ACNU was injected into the pleural space and pharmacokinetic behavior was studied. The clearance curves of ACNU in pleural fluid were described by either one-compartment model or two-compartment model. The mean half life of slow phase was 0.75 hour. These results indicate that ACNU disappears rapidly from the pleural space after the intrapleural administration. The effect of ACNU on the pleura was studied histologically in rabbits. At a dose of 3mg per kg body weight, the mesothelial cells were swelling and small areas of cellular desquamation appeared over the pleural surface. With increase in dosage, these findings were more pronounced and in the submesothelial tissue there was edema as well as cellular infiltration. In rabbits given two injections with interval of one week, the pleura showed a stronger reaction than that produced by single injection.

A new combination chemotherapy(VEPA) was applied to 9 patients with advanced and/or non-resectable primary gastric lymphoma. Among 6 patients with measurable disease, there were 3 (50%) complete responses and 1 (17%) incomplete response. None of 3 patients with lymph node and/or anastomosis involvements at the gastrectomy have relapsed after 13 months to 32 months. Complications during chemotherapy with VEPA were mild myelosuppression and gastrointestinal disturbances, and severe alopecia. Only one paralytic ileus with vincristine occurred, but no cardiotoxicities with adriamycin were observed. This study indicates that VEPA therapy is effective in the patients with primary gastric lymphoma.

AMSA, an acridine derivative with significant antitumor activity in experimental tumors, was administered to 17 patients with advanced tumors refractory to standard chemotherapies. A phase I study was undertaken in 10 patients with solid tumors and lymphomas. Dose-limiting toxicity was myelosuppression. With a median dose of 90 mg/m2 (75-148 mg/m2), median lowest WBC count was 1,000/mm3 (100-3,200) on day 11 and its recovery up to 4,000/mm3 was seen on day 21, while lowest platelet count was 42 X 10(3)/mm3 (7-300 X 10(3) on day 12 and its recovery up to 100 X 10(3)/mm3 was on day 20. Non-hematological toxicities were nausea (39%), vomiting (11%) and phlebitis (17%) in 18 courses of therapy. The result indicated that the recommended dose schedule for a phase II evaluation was 90 mg/m2, every three weeks. Therapeutic activity was observed in patients with non-Hodgkin's lymphoma (one partial response and two minor responses out of four). Two out of five breast, one ovarian, and one melanoma patients showed stable diseases. Five leukemic patients (three AMLs, one MoL, and one blastic CML) were treated with AMSA, and in these cases cytoreduction of peripheral and bone marrow blasts was seen, but it was not adequate to induce remission. Further clinical trials with this agent are warranted, especially in patients with acute leukemia, lymphoma and breast cancer.

Forty-six cases with hematological malignancies were treated with vindesine sulfate (VDS); a new semisynthetic vinca alkaloid. Six cases with ALL, 5 cases CML in blastic crisis, 3 Hodgkin's disease (HD) and 4 non-Hodgkin's lymphoma (NHL) were treated with VDS alone. Five out of 6 cases ALL, 2 out of 5 CML in blastic crisis were induced into partial remission with VDS alone. All of 3 HD, and 4 NHL were induced in complete remission (CR) or partial remission (PR). Out of 5 cases AML in CR who received VDS as the maintenance therapy in combination with cyclophosphamide, 6-MP and prednisone, one case relapsed during the treatment, but other four cases maintained CR for 4 to 24 months. One case of APL in relapse, which was treated with VDS and 6-MP, reinduced into CR after one month. Out of 16 cases with malignant lymphoma treated by combination chemotherapy including VDS, eleven cases entered in CR or PR. Out of four cases in which the disease became refractory to vincristine (VCR) or vinblastine (VLB) clinically, two achieved PR. VDS was administered intravenously with 3 mg/body/week. When undesirable effect such as leucocytopenia was observed, the dose was reduced to 2-2.5 mg/body/week or 3 mg/body/2 weeks or month. Neurotoxicity (i.e. Paresthesia 21.7%), alopecia (21.7%), leucocytopenia (19.6%), constipation (10.9%) and fever (6.5%) were main side effects of VDS. The neurotoxicity of VDS, however, seemed far less intensive than VCR.

General discussions on the drug resistance of cancer cells were made from various points of view: (1) drug resistance as an unhereditary phenotype, (2) changes in the cell population during drug treatment, (3) acquired resistance and natural resistance, (4) general concepts on biochemical and pharmacological mechanisms for drug resistance, (5) common mechanism for concurrent resistance to DNA-intercalators and vinca-alkaloids, and (6) collateral sensitivity on a cellular basis.

NK-631 (Peplomycin) has an anti-tumor spectrum, equivalent to or higher than its analogue bleomycin and low toxicities to the lungs. Fourteen patients with advanced non-Hodgkin's lymphoma received NK-631 10 to 30 mg once or twice a week. As the results, there were 57.1% response rate of all patients. The response rate according to the immunologic classification were 100%(6/6 cases) for patients with non-T cell lymphoma and 25%(2/8 cases) for patients with T-cell lymphoma. On the other hand, we observed some toxicities such as transient fever in 64.3%, G-I tract symptoms in 21.4%, skin toxicities in 21.4% and pulmonary fibrosis in one case. This agent is considered to be one of the useful agents to non-Hodgkin's lymphoma especially non-T cell lymphoma.

The antitumor activity of mitoxantrone, a new anthraquinone derivative, was examined on 11 cell lines of ascitic hepatoma in Donryu rats. The antitumor effect of mitoxantrone was slightly weaker than other anthracycline agents. However, since the balance of antitumor effect and toxicity shows a somewhat different pattern between man and rat, it is inappropriate to conclude the value of this agent from our present test alone. The real effectiveness in man will become apparent only when this agent is used human tumors.

The present study was aimed at investigating the efficacy of a new oral anticancer agent, HCFU, that is, (1-hexylcarbamoyl-5-fluorouracil), against 14 cases of unresectable gastric cancers which were confirmed by the laparotomy. The daily dose was 600mg and given continuously as long as the patients could take the drug orally. The efficacy was examined by X-ray photographs according to the criteria for the judgement of direct effect of the chemotherapy for solid malignant tumor. For the diffuse invasive type of gastric cancer, the changes in the X-ray finding such as stiffness and poor elasticity of gastric wall and malignant relief were also taken into consideration for the judgement. Among 9 patients, in whom the efficacy was measurable, two cases showed "partial response (PR)", two cases were diagnosed as "no change (NC)" and other 5 cases were diagnosed as "progressive disease (PD)". Among 2 partial responders, 1 case showed 85.3% decrease of the tumor size on the X-ray film and the other, who had diffuse invasive gastric cancer, showed much improvement on the X-ray film described above. The survival was around 5 months in "progressive disease" group. On the other hand, the patients with the good response to HCFU such as PR patients and NC patients could obtain a relatively longer survival period.