Twenty-two patients with malignant lymphoma and its allied diseases, consisting of 6 with Hodgkin's disease, 10 with non-Hodgkin's's diffuse lymphoma, 4 with leukemic lymphosarcoma and 2 with immunoblastic lymphadenopathy, were entered into this study. The treatment schedule was intravenous drip infusion of the drug, at a dose of 2.3 to 5.4 mg/kg (150 mg to 300 mg/day), for consecutive 4 to 14 days. The total dose given ranged from 1050 to 2500 mg. Four of the 6 patients with Hodgkin's disease and 5 of the 10 patients with non-Hodgkin's diffuse lymphoma showed a good response. The response started from 3 to 7 days after beginning of BH-AC administration and remission induced by BH-AC persisted for 4 weeks. Clinical toxicities such as anorexia, nausea and vomiting were very mild, but hematological toxicities such as thrombocytopenia, leukopenia, and anemia were frequent especially in the patients who were totally given more than 2100 mg. This study suggested that malignant lymphoma responded definitely to single administration of BH-AC and that BH-AC might be a new useful drug for multi-combined chemotherapy of malignant lymphoma.

Eighteen previously untreated patients with squamous cell carcinoma of the lung were treated with a combination of a new bleomycin derivative, peplomycin and esquinon (PQ). One patient achieved a complete response (5.5%) and 5 patients a partial response (27.8%). Overall response rate was 33.3%. Median survival time of 6 patients with complete and partial response was 54 weeks and that of 12 patients with no change and progressive disease was 15 weeks. Toxicities included nausea and/or vomiting in 89%, fever in 61%, interstitial pneumonitis in 28% and leukopenia in 17%. PQ regimen appears to be effective in the treatment of squamous cell carcinoma of the lung.

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.

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.

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.

Prostaglandin D2 was found to have a potent cytotoxic effect on L1210 leukemia culture cells. When Prostaglandin D2 was added to the culture medium, at the concentration of over 5 micrograms/ml growth of L1210 cells was almost completely inhibited. IC50 of Prostaglandin D2 for L1210 cell was 2.4 micrograms/ml. Cells exposed this agent showed remarkable change in its cytoplasm with many vacuoles and lysis of cells were observed at the concentration over 5 micrograms/ml.

We have developed OMF treatment which is consisting of endoscopical injection of OK-432 into the perilesional area of cancer, intraarterial or intravenous injection of mitomycin C by one shot and oral administration of 5-FU, and applied it to the patients with preoperative gastric cancer to whom remarkable macroscopic effects were obtained. We determined its efficacy by establishing a response criteria. Although there were no excellent results, the clinical results were rated as good in 5 lesions (50%) and as fair in 5 lesions (50%) out of 10 lesions in 9 cases. In none of the cases, the treatment was ineffective.

Sakata, et al. has already reported that the combination therapy of mitomycin-C, carboquone, 5-fluorouracil and OK-432 (MQF-OK therapy) which had established from animal experiments, was exceedingly effective for inoperable human gastric cancer. In this paper, the effectiveness of MQF-OK therapy for inoperable gastric cancer was compared with that of MFC therapy. To perform this controlled study, a "large area" co-operative study group of cancer chemotherapy, composed of 14 institutions in Aomori and a part of Akita prefectures, was organized. From April 1977 to April 1980, patients were registered and 61 cases were evaluable; 31 out of 61 were treated with MQF-OK therapy (MQF-OK group) and the others with MFC group. The background of the cases, such as sex, age etc, was not different significantly between two groups statistically. According to the response criteria of Japan Society for Cancer Therapy, 18 cases out of 31 cases of MQF-OK group and 9 of 30 cases of MFC group showed "improvement." According to Karnofsky's criteria 17 cases of MQF-OK group and 8 of MFC group showed effectiveness more than I-A, respectively. There was a statistical significance between the two groups (P less than 0.001). By Kaplan-Meier's method, the MQF-OK group survived longer than the MFC group (P = 0.05). The complications, such as leukocytopenia, thrombocytopenia or gastrointestinal complaints, were more frequently found in MQF-OK-432 group than in MFC group (P less than 0.05). But these complications decreased or resolved spontaneously 1 to 4 weeks after the administration of MQF-OK therapy. On these results, MQF-OK therapy was considered excellent method for treatment of inoperable gastric cancer and will be furthermore attempted against other cancers.

The malignant ovarian cancer cells removed on operation were cultured and exposed to the anticancer drug (either 5-fluorouracil or mitomycin C) for 30 minutes or 24 hours respectively. The activity of the LDH and LDH isozyme in the culture medium was measured. Also the activity of the LDH and its isozyme was determined in the patients undergoing chemotherapy with either 5-fluorouracil or mitomycin C. The results are summarized as follows: 1) The LDH isozyme pattern of the culture medium prior to exposure of malignant cells to the anticancer drugs was classified into 2 types i.e., M type which is characterized by a predominance of LDH4,5 (referred hereinafter to as group M) and H type with a predominance of LDH1,2 (referred to as group H). 2) Of 11 cases studied, 7 were classified as group M and 4 were categorized as group H. there was no distinct relationship between histological type and LDH isozyme pattern. 3) In the group with exposure to anticancer drugs the total LDH activity in both group H and group M was lower than in the control group. Control specimens in group H showed increased total LDH activity. 4) The H/M ratio based on subunits of LDH isozyme was virtually unchanged by exposure to anticancer drugs in group M, while rapidly lowered by the same treatment in group H. 5) The death rate of malignant cells as estimated by dye exclusion methods was higher with exposure to anticancer drugs than without it. 6) The serum LDH was more markedly lowered after treatment in group H than in group M. However, there was no substantial difference between the two groups in M/H ratio before and after treatment.