The effects of chemotherapy for lung metastasis in 284 cancer patients using various anti-tumor drugs, including classic ones and modern active agents for the past 18 years, were presented. Lung metastasis for lung cancer was excluded. The response was achieved in cervical carcinoma of the uterus (17/62, 27%), endometrial carcinoma of the uterus (1/7, 14%), colorectal cancer (6/39, 15%), breast cancer (5/28, 18%) and stomach cancer (4/28, 14%). A high response was achieved in myosarcoma (5/12, 42%), testicular cancer (5/11, 45%) and also in ovarian cancer (3/10, 30%). Though there were few cases, a high response was achieved in malignant melanoma (2/3), choriocarcinoma (2/4) and esophageal cancer (1/3). In total patients the response rate was 20%. In these cases a complete response was achieved in 4 cervical cancers; one testicular cancer, ovarian cancer, esophageal cancer and renal cancer, respectively. However, the effect was temporary and no longterm survivor was observed except for one case of renal cancer treated continuously with interferon (3 X 10(6) units daily) and showing complete remission after 7 months of therapy. The effect of chemotherapy for lung metastasis was compared between nodular metastasis (NM) and lymphagiosis carcinomatosa (LC). In cervical carcinoma of the uterus, the response rate in NM (39%) was higher than in LC (11%). However, no difference was observed in breast cancer (NM 15%, LC 13%) nor in stomach cancer (NM 13%, LC 18%).

One hundred and sixty-five patients of choriocarcinoma were treated during the period from 1957 to 1979. Pulmonary metastases were found in 111 of the 165 patients. The authors found that surgical intervention for pulmonary metastasis was an extremely effective means for the patients who were not cured by chemotherapy and satisfied the criteria that we newly established for surgery. All patients satisfied the criteria achieved primary complete remission and their three years survival rate was 80%. The timing for surgery was also discussed and it was concluded that pulmonary surgery should be adopted when patient's urinary hCG values persisted at the level below 1000 iu/l for 70-80 days period.

Ninety-seven pulmonary metastatic cases in 141 osteosarcoma from 1960 to 1981 were analysed. The overall cumulative 5-year survival rate of the cases was 38.1%, whereas that of the recent 41 cases with systemic chemotherapy was 56.2%. Eighty percent of pulmonary metastases were found within one year since their first visit to our clinic. It was revealed that there were positive relationship between the doubling time of the pulmonary metastases and the post-metastatic survival (p less than 0.001), and between the period from their first visit to our clinic to metastases and the post-metastatic survival (p less than 0.001). The favorable effects of the systemic chemotherapy using adriamycin, vincristine, methotrexate and cis-platinum were recognized. The thoracotomy revealed effective and five cases are living without disease for average 80.8 months after surgery.

ACNU, GANU and MCNU, water-soluble nitrosoureas, have been evaluated in terms of influence of treatment schedule on antitumor activity in mice bearing L1210 leukemia. The results obtained were as follows: 1) ACNU produced a significant increase in life span and long-term survivors by administration on day 1 only, once every 8 days for 2 doses or once every 4 days for 3 doses, and the compound was most effective when given on day 1 only. 2) GANU produced a significant increase in life span and long-term survivors by same administration schedules as ACNU, and the compound was most effective when given every 8 days for 2 doses. 3) MCNU produced a significant increase in life span and long-term survivors by each administration including daily treatment, and the compound was most effective when given every 4 days for 3 doses. 4) ACNU and MCNU displayed the same level of activity as CCNU when the drugs were given on day 1 only. Daily treatment with MCNU was as effective as daily treatment with CCNU. Our results suggest that ACNU, GANU and MCNU should be administered by intermittent schedule as lipid-soluble nitrosoureas such as BCNU, CCNU and MeCCNU.

We analysed the effects of three different regimens for first induction therapy with 50 cases of acute nonlymphocytic leukemia in adults and reported the results of combination therapy including aclacinomycin for reinduction therapy. Results obtained were as follows: The regimens of DCMP 2 step and Cc, P were superior to DCMP in remission rate (78%, 78% and 41%), median duration of CR (8.3 months, 5.0 months and 3.5 months) and survival time (6.5 months, 11.5 months and 2 months). Cc, P regimens obtained favorable CR rate in elderly patients over 50 years of age. (Cc, P: 100%, others: 40-50%) No significant difference in survival time was observed in patients who attained CR by three different regimens. In patients treated with combination therapy including aclacinomycin, the CR rate was 89% in the 9 previously treated patients (5 relapse cases and 4 refractory leukemias): All of these patients had previously been treated with DCMP 2 step or BHAC-DMP. Daunomycin (D), Cytosine Arabinoside (C), 6-Mercaptopurine (M) and Prednisolone (P) (DCMP), DCMP 2 step and Cyclocytidine (Cc) P.

Eight esophageal squamous cell cancer patients were treated with local hyperthermochemotherapy plus ethanol in addition to bypass surgery and supraclavicular esophagostomy. Local hyperthermochemotherapy plus ethanol treatment was as follows: The esophagus was perfused for one hour using esophagostomy with warmed saline (42-44 degrees C) containing 6-10% ethanol, the overflowing saline was aspirated. Simultaneously, 15 mg Bleomycin or 10 mg Peplomycin was administered intravenously and 5 mg Bleomycin or Peplomycin was administered directly to the esophageal site. This procedure was repeated twice a week for a total of 10 to 24 times. Six of the 8 patients (75%) thus treated showed a shortening of the duration of the shadow defect in X-radiograms. In one case, the lesion was removed and the patient is doing well 9 months after the operation.

Potentiation of the cytotoxic effects of various anticancer agents by interferon on human malignant cells was examined in culture. The human neoplastic cells used were HeLa cells derived from uterine cervical cancer. The interferon was produced in human diploid fibroblasts treated with Poly I:C. Anticancer drugs examined were as follows; antibiotics (aclacinomycin, actinomycin D, adriamycin, cycloheximide, mitomycin C, peplomycin, puromycin), antimetabolites (cytosine arabinoside, 5-fluorouracil, 6-mercaptopurine, methotrexate), alkylating agents (ACNU, melphalan), and others (cisplatin, hydroxyurea, vincristine). The cytotoxic effects were determined by colony formation. Our results demonstrated that interferon potentiated significantly the cytotoxic effects of peplomycin, aclacinomycin, cisplatin, 5-fluorouracil, and adriamycin on HeLa cells. The present results indicate that a combined administration of interferon and these drugs may be effective in the treatment of human cancers.

Nineteen patients with advanced non-Hodgkin's lymphoma (NHL) (stages III and IV) receiving no prior chemotherapy were treated with a combination of cyclophosphamide, adriamycin, vincristine, bleomycin and prednisolone (CHOP-Bleo) at Saitama Cancer Center between January 1977 and February 1979. The overall complete response rate was 11 of 19 or 50%, with 8 of 13 or 62% of patients with diffuse mixed and large cell type of NHL. The median survival for all patients was 41 months. The survival curve of complete responders became flat at 41 months and was well sustained with an actuarial survival of 72%. The survival of patients with stage III was significantly better than those with stage IV (p less than 0.05), while the survival of patients with Waldeyer's ring primary was not significantly superior to patients with nodal primary. A major complication during CHOP-Bleo regimen was myelosuppression, and peripheral neuropathy and reversible interstitial pneumonitis (2 cases) were also observed.

Determinations of pregnancy-associated alpha-glycoprotein and immunosuppressive acidic protein in sera of patients have improved a detection rate of ovarian cancer in the early stage. In the clinical treatment of ovarian cancer, we employed the regimen based on results of experimental chemotherapy using heterotransplanted human tumors of the ovary. A regimen of cis-platinum, adriamycin and 5-fluorouracil combination in epithelial tumors and a regimen of cis-platinum, vinblastine and bleomycin combination in germ cell tumors may be recommended for treatment of ovarian cancer.

A concept of antitumor screening with rodent tumor models is discussed through the experience in the past 30 years, together with an introduction of a new system of antitumor screening in NCI, U.S.A., including a recently adopted mouse ovary tumor model. It is suggested that the more minute and elaborate studies of mode of action of the effect and toxicity of the antitumor drugs which are already clinically evaluated are useful to get new structures of compounds with antitumor activity into our minds. A new approach in studying drug resistance of tumor cells proposed by Ling is introduced that some of the acquired drug resistance is closely related to natural resistance of tumor cells which occurs by spontaneous mutation of the cells during proliferation.

Recurrent breast cancer can now be treated more effectively with endocrine therapy, combined with chemotherapy. Between April 1977 and March 1982, 127 breast cancer operations were performed at Kumamoto Municipal Hospital; recurrence was found in 13 cases (approx. 10%). Treatment of 7 of these cases with endocrine therapy (mainly Nolvadex, anti-estrogen) combined with chemotherapy resulted in 6 cases showing either complete response (CR) or partial response (PR). The efficacy of chemo-endocrine therapy was obvious when compared with cases without therapy. Further studies on hormone receptors and the establishment of guidelines for chemo-endocrine therapy as post-operative adjuvant therapy are justified.

Since July 1980, thirty patients with inoperable adenocarcinoma of the lung have been treated with ANV. Induction chemotherapy (Adriamycin 35 mg/m2 i.v. days 1 and 22, ACNU 2 mg/kg i.v. day 1, vindesine 2 mg/m2 i.v. days 1, and 22) was given for 2 courses (or 1 course) at 3-week intervals. Maintenance chemotherapy was performed with reduced doses and elongated intervals. Characteristics of 30 patients were as follows: 13 males and 17 females; mean age 55 (range 32-77); mean PS 1.6, prior chemotherapy 3 cases; tumor involving bone (53%), brain (20%) and cervical node (23%). Of 27 patients who received no prior chemotherapy, 2 patients were unmeasurable because of pleural effusion. After one course of induction chemotherapy, 7 out of 25 patients achieved PR (response rate: 28%), 5 MRS (20%), 10 NCS, and 3 PDS. When patients were divided into the youngers (32-59 years old, mean 47) and the older (60-77 years old, mean 67), the youngers showed apparently higher response rate (6/17, 35%) than the olders (1/8, 13%). When patients were divided into three groups by the grade of cell differentiation, response rates were 0/5 (0%) in the well differentiated group, 2/6 (33%) in the moderately differentiated group, and 5/11 (45%) in the poorly differentiated group. The median survival time for all patients was 9 months; the younger 8 months, the older 9 months, well differentiated 11 months, moderately differentiated 9 months, and poorly differentiated 7 months. Survival time of responders was not significantly (P greater than 0.05) longer than that of non-responders. Toxicities were mild: leucopenia (less than 4,000) found in 85%, thrombocytopenia (less than 100,000) in 8%, anorexia in 54%, nausea and vomiting in 39%, and alopecia in 82%.