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.

It has been reported that flow cytometric analysis offers good indicators to select drugs for chemotherapy of malignant neoplasms, however, there are still few reports to try to apply these data to clinical treatment. For this purpose perturbation of cell cycle traverse which induced by several anticancer drugs was studied to determined the fundamental factors to indicate the sensitivity of each drugs. Results were: 1) Drugs showed high efficiency of accumulation of cells in SG2M phase even in low concentration; MMC, AD, CQ. 2) Drugs showed high efficiency of accumulation of cells in SG2M from low concentration high concentration; Vincristine. 3) Drugs which showed accumulation of SG2M in high concentration; ACNU, BCNU. 9L rat glioma cells treated with BCNU showed high efficiency of accumulation of cells in SG2M phase. In this cell line cytocidal effect was high. However, C6 cells which showed low accumulation in SG2M even by treatment with high concentration of BCNU revealed quite resistant to anticancer drugs from nitrosourea derivatives (ACNU, BCNU). Cytocidal effect of MMC and ACNU on C6 glioma cells was studied by colony forming efficiency assay using multicell spheroids treated with these drugs and it was discussed the correlation between percent of accumulated cells and cytocidal effect of each drug.

Effect of various anticancer drugs on in vitro survival of gynecologic tumor cells were investigated by using established cell lines derived from human ovarian adenocarcinoma (HOC-21), endometrial adenocarcinoma (HEC-1B), and cervical squamous cell carcinoma (SKG-1). As compared with other established cell lines, 1) HOC-21 cells were more sensitive to Cis-platinum, Adriamycin, and actinomycin-D. 2) HEC-1B cells were more sensitive to progesterone. 3) SKG-1 cells were more sensitive to bleomycin and mitomycin-C. These results are consistent with the clinical effects of various anticancer drugs, and established cell lines derived from various human gynecologic tumors are useful to select effective anticancer drugs in vitro.