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Streptococcal agent OK-432 was administered a t maintenance levels with conventional inductive chemotherapeutic agents to stage 111 and I V lung cancer patients. Survival rates were longer in patients treated with OK-432 than in patients treated without OK-432. An enhancement of lymphocyte blastogenic activity and a delayed PPD skin reaction were found i n patients treated by OK-432. A low grade fever was present as a side effect of this agent in some patients. T h e results suggest that OK-432 may be a useful immunotherapeutic agent i n combination with induction chemotherapy in reducing host damage in advanced stages of lung cancer. Cancer 37:2201-2203. 1976. KAMOTO ET AL.'s8 DEVELOPED STREPTOCOC-0 cal agent OK-432 and suggested that this agent destroyed cancer cells. This drug has been shown to have a positive effect in a limited number of patients with leukemia and car-cinoma but no conclusions could be drawn as to the relationship between dose and effect.*Vs Our previous studies4~5~"J have suggested that OK-432 may have a mild anticancer response but the principal effect of this agent appeared to be on cell-mediated action and on reticuloendothelial function, and n o effect was observed on humoral immunity. I n our earlier studies485 tumor cells were implanted in mice pretreated with OK-432. Host resistance to implanted tumors continued after drug administration for at least 1 week. I n these mice, pretreatment with OK-432 accompanied by concomitant treatment with either cyclophosphamide or irradiation resulted in reduced survival time compared with pre-treatment by OK-432 alone. T h e length of host survival appeared to be related directly

In order to evaluate the preventive efficacy, safety and usefulness of mesna (Sodium 2-mercaptoethane sulfonate) against ifosfamide-induced urinary disorders, a placebo-controlled double-blind comparative study was performed. Ifosfamide was administered by intravenous drip infusion at a daily dose of 2 g/m2 for 5 consecutive days, and mesna was intravenously administered at 20% of the ifosfamide dose, three times daily for 5 consecutive days. The results obtained are as follows. (a) Of 101 accrued patients, 91 patients were evaluated consisting of 45 for the mesna group and 46 for the placebo group. There was no intergroup difference in the number of the evaluated cases and patient characteristics. (b) Micturition pain and feeling of residual urine graded as moderate or severe were not observed for the mesna group, but were observed for the placebo group with incidences of 19.6% (9/46) for micturition pain and 15.2% (7/46) for feeling of residual urine; the intergroup differences in the appearance of these urinary symptoms were statistically significant (P = 0.0003 for micturition pain; P = 0.0009 for feeling of residual urine). The incidence of hematuria graded as moderate or severe was 6.7% (3/45) in the mesna group, which was significantly lower than the 32.6% (15/46) in the placebo group (P = 0.0008). (c) No side-effect attributable to mesna was observed. (d) A judgment of "useful" was obtained in 80.0% (36/45) of the patients treated with mesna, which was significantly higher than the 34.8% (16/46) of the patients treated with placebo (P = near 0). On the basis of the above results, we conclude that the preventive efficacy, safety and usefulness of mesna against ifosfamide-induced urinary disorders have been well demonstrated in this study.

Weinvestigated the changes in cellular components and neutrophil chemotactic factors in pleural fluid from 19 lung cancer patients who received intrapleural injection of OK-432 to treat malignant pleurisy. Not only neutrophil chemotactic activity (NCA) but also neutrophil count and percentage were increased significantly at 6 hours after OK-432injection. The neutrophil count was significantly correlated with NCAlevel. The levels of C5a and IL-8 in pleural fluid were increased significantly after OK-432 injection. The increased IL-8 level was associated with a increase of both NCAand neutrophil count. OK-432 treatment also induced a marked increase of IL-lfi and IL-6 in pleural fluid. Thus, intrapleural injection of OK-432 induced production of neutrophil chemotactic factors (IL-8 and C5a) and cytokines (IL-lfi and IL-6), which eventually attracted neutrophils into the pleural space. These observations suggest that neutrophil migration mediated by these factors and cytokines may contribute to the sclerosing effects of OK-432 treatment. (Internal Medicine 34: 352-356, 1995)

Background. Small cell lung cancer (SCLC) is highly sensitive to chemotherapy. Despite the introduction of intensive combination chemotherapy, long‐term disease‐free survivors are still rare. The emergence of drug‐resistant tumor cells during chemotherapy is presumed to be the major cause of poor outcome. Methods. A pilot Phase II study of hybrid chemotherapy for patients with SCLC was conducted between October 1986 and March 1988. Dose and schedule for each drug in the regimen were as follows: cyclophosphamide, 700 mg/m2 intravenously (IV), day 1; doxorubicin, 30 mg/m2 IV, day 1; vincristine, 1.4 mg/m2 IV, day 1; cisplatin, 60 mg/m2 IV, day 8; and etoposide, 100 mg/m2 IV, days 8 and 9. Courses were repeated every 4 weeks for up to six cycles. Patients with limited disease (LD) received chest irradiation of 5000 cGy when a maximal response was achieved. Only patients with LD who achieved a complete response (CR) received prophylactic cranial irradiation of 3000 cGy. Results. Thirty‐six patients were enrolled and fully evaluated for tumor response and toxicity. All 20 patients with LD responded to the regimen, and 14 (70%) of those achieved a CR. Of 16 patients with extensive disease (ED), 7 CR and 7 partial responses were noted, indicating an overall response rate of 88%. The median survival time was 23.6 months for patients with LD and 12.6 months for those with ED. Myelosuppression was the major toxicity, but it was generally well tolerated. Conclusions. These results indicate that the hybrid regimen is a highly active one for the treatment of patients with SCLC and warrants additional clinical trials.