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The benefits of immunochemotherapy with a penicillin-treated, lyophilized preparation of Streptococcus pyogenes, OK-432 (Picibanil), were reassessed in patients with resected non-small-cell lung cancer through a meta-analysis based on data from 1,520 patients enrolled in 11 randomized clinical trials. All 11 trials were started before 1991, and the subjects had been followed up for at least 5 years after surgery and randomization. In these trials, standard chemotherapy was compared with the same therapy plus OK-432. The endpoint of interest was overall survival, and analysis was based on intent-to-treat population without patient exclusion. Data were analyzed using the Mantel-Haenszel method. The 5-year survival rate for all eligible patients in the 11 trials was 51.2% in the immunochemotherapy group versus 43.7% in the chemotherapy group. The odds ratio (OR) for overall survival was 0.70 (95% CI = 0.56-0.87, p = 0.0010). Analysis of four trials in which central randomization was performed also reconfirmed a significantly longer survival time for the immunochemotherapy group (OR = 0.66, 95% CI = 0.44-1.00, p = 0.049). Based on these results of meta-analysis, it is postulated that postoperative adjuvant immunochemotherapy using OK-432 might improve the survival of patients after resection of non-small-cell lung cancer.

In this study, we defined a solitary lung nodle in the same histology which could be traced its' origin from carcinoma in situ or was found over than two years' follow up as a second primary lung cancer. These cases were excluded. Eighteen cases underwent second surgery for intrathoracic recurrence. Fourteen cases were male and four cases were female. Their ages ranged from 23 to 75 (average 59.6) years. The histology were adenocarcinoma in 9 cases, squamouscarcinoma in 7, adenosquamous carcinoma in 1, large cell carcinoma in 1. The initial surgical procedures were lobectomy in 17, partial resection in 1. The initial stage were I in 13, II in 2, IIIA in 1. Pulmonary recurrence were found in 10, bronchial stump recurrence were found in 4, pulmonary hilus lymph node recurrence were found in 2, mediastinal lymph node recurrence were found in 2, pulmonary stump recurrence was found in 1. The second surgical procedures were completion pneumonectomy in 7, completion lobectomy in 1, lobectomy with segmentectomy in 1, segmentectomy or partial resection in 7, mediastinal dissection in 2. The overall 5-year survival rate of the patients with recurrence after reoperation was 31.8%. An aggressive surgical approach for recurrent lung cancer should be recommended.

Ninety seven patients with metastatic lung tumors were treated surgically in our department. Second pulmonary resections were performed in 13 patients. They consists of 9 males and 4 females, their age ranged from 12 to 75 years old (average 54.4 years old). Tumors originate from sarcoma in 5 cases, laryngeal cancer, colorectal cancer, renal cell cancer in 2 cases respectively, oral cavity cancer and transitional cell cancer in 1 case respectively. No second pulmonary resection was performed in patients with metastatic lung tumors originating from lung cancer or breast cancer, because they metastatize not only lung but also general organs. No second pulmonary resection was required in patients with testicular tumor and choriocarcinoma, because chemotherapy take good effect on them.

Our studies of the degradation and the phosphorylation of 5-fluorouracil (5-FU) in normal and tumor lung tissues from 10 cases of lung cancer have shown that the phosphorylation of 5-FU in the tumor tissues was about 2- to 3-fold higher than that in normal tissues, and that the degradation of 5-FU in tumor tissues was nearly 6-fold higher than that in normal tissues. BOF-A2 is an anti-neoplastic agent newly synthesized from 1-ethoxymethyl-5-FU and 3-cyano-2,6-dihydroxypyridine (CNDP). The inhibitory effect of CNDP on the degradation of 5-FU in the tumor tissues was potent (IC50 3.9 x 10(-9) M). Thus, BOF-A2 exerts its anti-neoplastic effect on tumors by potentiating the action of 5-FU through inhibition of 5-FU degradation by the CNDP moiety.

In this study, we evaluated 15 surgically treated cases of lung cancer with scalene node metastasis. Eleven males and 4 females with ages ranging from 41 years to 78 years (average 59.1 years) were examined. Seven cases was in the right upper lobe, 3 in the left upper lobe, 2 in the right lower lobe, 2 in the left lower lobe, 1 in the middle lobe. Adenocarcinomas were found in 9 cases squamous cell carcinomas were in 4 cases and large cell carcinomas were in 2 cases. Two cases was in T 1, 7 in T 2, 2 in T 3, 4 in T 4. In all cases, lobectomy was performed. Five year survival rate was 14.3% as determined by the Kaplan-Meier method. Average survival period was 26.6 months. Three cases survived over 3 years including one case survived over 10 years.

In this study, we evaluated 16 surgically treated cases of metastatic lung tumors originating from renal cell carcinoma. Ten males and 6 females with ages ranging from 31 years to 74 years (average 60.8 years) were examined. Five cases had solitary metastasis, 4 had ipsilateral multiple metastasis, and 7 had bilateral metastasis. The average number of lung metastatic legion was 3.3. Disease free intervals ranged from 0 to 120 months (average 22.6 months). Tumor doubling time calculated in only 8 cases, ranged from 36 to 510 days (average 126 days). In 8 cases, tumor doubling time could not be calculated because tumor growth was too slow. Partial resection or segmental resection was performed in 14 cases, 8 with ipsilateral and 6 with bilateral lung metastasis. Lobectomy was performed in only two cases. Five year survival rate was 43% as determined by the Kaplan-Meier method. We believe that such cases possessing a slow tumor growth rate have a better survival rate.

We conducted a prospectively controlled study of adjuvant immunochemotherapy for resectable lung cancer in 37 cases of the control group, in 34 cases of levamisole group and in 40 cases of OK-432 group. No significant difference was noted in patient characteristics of age, sex, histological type, stage, cure rate, etc. The survival rates were calculated by Kaplan and Meier method. Survival curves were measured by generalized Wilcoxon test and Cox-Mantel test. When the levamisole group and the control group were compared in terms of survival rate, a significant increase of survival curves of patients treated with levamisole was observed in surgicopathological stage III + IV and relative curative operation groups (p less than 0.05). The survival rate of levamisole group was higher than that of OK-432 group in patients of surgicopathological stage III and III + IV (p less than 0.05). There was no statistically significant difference between OK-432 group and the control group, when in survival rates.

It is well known that UFT has significant therapeutic effects against experimental and clinical cancers at the primary sites. In this experiment, we studied the inhibitory effect of UFT on the lung metastasis of spontaneously developed rat mammary carcinoma (SST-2) after surgical excision of the primary site. In comparison of UFT-treated (15 or 30 mg/kg/day) with 5-FU-treated (9.7 or 19.5 mg/kg/day) groups, UFT was more effective than 5-FU in the antitumor activity and the inhibitory effect of lung metastasis with/without surgical excision of the primary sites. Rats (5-10 rats per group) were inoculated s.c. with 1 x 10(6) SST-2 cells and administered with UFT orally (15, 30 or 60 mg/kg/day) starting the day after tumor inoculation for 30 days. The therapeutic effect of UFT was studied by the growth rate of primary tumor and the numbers of metastatic colonies in the lung 35 days after tumor inoculation, comparing the UFT-treated with control groups. UFT administration at the doses of 30 or 60 mg/kg/day markedly inhibited the growth of the primary tumors and the number of metastatic lung colonies decreased, compared with that of the control group. However, in the group of rats treated at the dose of 60 mg/kg/day, 60% of rats died from the side effects of UFT such as weight loss, hemorrhage etc. In all groups in which the primary tumors were surgically excised 20 days after tumor inoculation and then treated with UFT (15, 20 or 30 mg/kg/day), we observed marked prolongation of survival period and inhibition of lung metastasis as well. Furthermore, we studied the effect of combination therapy of UFT and lentinan (1 mg/kg/day i.p.) on the metastasis of SST-2 cells after surgical excision of the primary sites. It was more effective than UFT alone. Thus, it is clear that UFT is an effective anticancer drug to inhibit metastasis of tumors in the lung after surgical excision of primary tumor.

A 37-year-old female, who had undergone a left standard mastectomy in May, 1983 for breast cancer, was treated with Tamoxifen and FT-207 postoperatively. The patient had no further evidence of disease until two and one-half years later, when a routine chest film showed a single, half-rounded density 6.5 cm in diameter in the hilus of her left lung. Bestrabucil, the benzoate of an estradiol-chlorambucil conjugate, was administered p.o. at a daily dose of 200 mg for four weeks. Thereafter, the tumor greatly decreased in size to 3.0 cm in diameter. When a left upper lobectomy was performed, the tumor was found to be necrotic tissue. Microscopically, a small cancer nest similar to the primary breast carcinoma was observed in the center of the necrosis. The necrotic tissue was surrounded with cellular infiltrate, markedly consisting of histiocytes.