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BACKGROUND/PURPOSE: Twenty-two institutes have organized Keio University Prostate Cancer Study Group to study clinical efficacy and safety of Leuprolide acetate (Leuplin) for the treatment of advanced prostate cancer (clinical stage D1 and D2). Cotreatment of Leuplin and Estramustine phosphate disodium (Estracyt) has been performed to investigate its clinical efficacy. MATERIALS AND METHODS: One hundred and two cases of advanced prostate cancer were treated either with Leuplin alone (group I), Leuplin and Estracyt (group II) or Estracyt alone (group III). After 12 weeks treatment, clinical effects against subjective symptoms (pain, voiding difficulty, performance status and body weight), serum testosterone level, tumor size and serum PSA level were examined to investigate short-term effect of each treatment. The treatment had been continued for 24 months and the treatment effects including progression free survival and overall survival were analyzed. RESULTS: Clinical efficacy after 12 weeks treatment were examined among 97 cases (group I; 35 cases, group II; 36 cases, group III; 26 cases). The background of those patients in each group was statistically equal. Treatment effects against subjective symptoms and serum testosterone level statistically revealed no significant difference among 3 groups. Treatment effects against primary tumor, bone metastatic lesion, lymphnode metastatic lesion and serum PSA level were investigated and anti-tumor effect was characterized by total efficacy rate (complete remission rate plus partial remission rate) of each treatment group. Treatment efficacy rates for each lesion and PSA demonstrated no statistical difference among 3 treatment groups. Total efficacy rate of group I, II and III were 88.2%, 84.0% and 78.3%, respectively, which statistically revealed no significant difference. Total efficacy rate of each group after completing 24 months treatment was; group I 80.0%, group II 55.6% and group III 83.3%, which statistically showed no significant difference among 3 treatment groups. The median day for progression free survival of group I, II and III were 661, 731 and 517, respectively. The overall survival rate of group I, II and III after completing 24 months treatment were 77.5%, 83.0% and 72.4%, respectively. Both progression free survival rates and overall survival rates revealed no significant difference among 3 groups. Side effects during 24 months treatment were seen in 8.6% of group I, 47.2% of group II and 26.9% of group III, and these occurrence rates were significantly different among the groups (p = 0.0013). CONCLUSION: Although number of the cases had not been able to continue the treatment for their side effects, the statistical characterization demonstrated that cotreatment of Leuplin and Estracyt had no greater treatment effect than monotreatment of each drug.

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Ample evidence confirms that certain cancer cells have the capacity to produce multiple peptides as growth factors and that expression of their receptor may act in tumour cell paracrine and/or autocrine loop mechanisms, either by extracellular release of the growth factor or by the tumour itself. To study the possibility of an autocrine growth mechanism in bladder carcinoma, we investigated the ability of various bladder carcinoma cell lines to proliferate in serum-free medium. A rat bladder carcinoma cell line, BC47, demonstrated exponential and density-dependent growth in serum-free medium. Furthermore, conditioned medium from BC47 cells induced growth-stimulating activity for BC47 cells themselves. Purification and further characterization of this activity was performed by chromatographic methods, SDS-PAGE and N-terminal amino acid analysis. Finally, we have identified that a transferrin-like 70-kDa protein is found to be the main growth-promoting factor in this conditioned medium. In addition, specific antibodies against transferrin and the transferrin-receptor inhibit the in vitro growth of this cell line. Our data suggest that this transferrin-like factor possibly acts as an autocrine growth factor for cancer cells.

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Between 1980 and 1985, 17 patients with advanced urothelial carcinoma and 13 with metastatic prostatic carcinoma refractory to hormonal therapy were treated with a combination chemotherapy of cyclophosphamide (CPM), adriamycin (ADM) and cis-diammine-dichloroplatinum (CDDP) to evaluate its antitumor effect and toxicity. ADM (1 mg/kg) on day 1, CPM (2 mg/kg) on days 2 through 5 and CDDP (1.5 mg/kg) on days 6 and 7 were administered every 3 weeks. Of the 17 patients with urothelial carcinoma, 13 were eligible for evaluation. One patient achieved CR with a disease-free interval lasting for 29 months, one showed PR (duration of response 2 months), 4 NC and 7 PD, with an overall response rate of 15% (2/13). Of the 13 patients with prostatic carcinoma, 11 could be evaluated. No patients achieved CR, one had PR (duration of response 5 months), 2 NC and 8 PD, with an overall response rate of 9% (1/11). No statistically significant difference in survival was noted between responders (CR + PR) and non-responders (NC + PD) to the combination chemotherapy, irrespective of whether they had metastatic urothelial or prostatic carcinoma. Myelosuppression was frequently noted, with sepsis occurring in one patient. No mortality attributable directly to this regimen was noted.

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A case of gastric cancer which contained a part of choriocarcinoma was reported in this study. The patient was a 64-year-old man, who was operated on with the diagnosis of gastric cancer in the prepyloric region. The postoperative histological examination revealed that typical choriocarcinoma was noted in a part of the adenocarcinoma, which occupied almost the entire portion of the surgical specimen. In addition, the precise localization of human chorionic gonadotropin (hCG) in the portion of choriocarcinoma was proved by the indirect immunoperoxidase stain (PAP method). The patient showed the gynecomastia clinically. The concentration of postoperative serum hCG was elevated and testicular abnormality was not noted clinically.

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