[5-Fluorouracil and alpha-2a interferon in patients with hormone-refractory prostate cancer].

BACKGROUND: Hormone-refractory metastatic prostate cancer remains a disease for were limited therapeutic options are available. Therefore, the establishment of newly, more effective chemotherapy is expected. Experimental data suggest that PC-3, a human hormone refractory prostate cancer cell line, showed a 2-fold increase in 5-Fluorouracil (5FU) sensitivity in the presence of alpha-2a Interferon (IFN alpha 2a) at 100 IU/ml, compared to that without IFN alpha 2a. Based on this data, we treated 11 patients with 5FU and IFN alpha 2a in order to determine the clinical response and toxicity of this combination chemotherapy. METHODS: One course of this combination chemotherapy consisted of a continuous intravenous infusion of 5FU at 600 mg/m2/day for 5 days (D1-D5) with IFN alpha 2a 3 million units (MU) intramuscularly 3 times weekly (D1, D3, D5) followed by a bolus injection of 5FU at 600 mg/m2 and IFN alpha 2a at 3 MU/day on D15 and D22. RESULTS: Based on the Response Criteria for Prostate cancer Treatment, one of 9 patients with bony metastasis had partial response, 2 patients with nodal disease on the CT scan obtained partial response. Six of 11 patients had more than 50% decrease in post-therapy prostatic antigen levels, 3 of whom obtained complete response. Significant myelosuppression did not occur. There were no chemotherapy-related deaths. CONCLUSION: These results suggest that the combination of 5FU and IFN alpha 2a, although preliminary, is an active regimen against hormone-refractory metastatic prostate cancer.

Suppression of cold-induced thermogenesis in full-term pregnant rats.

1. Thermoregulation against cold exposure was studied in rats during pregnancy and early lactation, and compared with that of virgin rats. 2. When exposed to 0 degrees C for 60 min, rats which were within 24-48 h of parturition (pre-1-day rats) and those within 24 h of parturition (pre-0-day rats) showed significantly larger falls of colonic temperature (Tco) than virgin rats. The temperature decrease was greatest in the pre-0-day rats, being 4.1 +/- 0.4 degrees C (mean +/- S.E.M.) at the end of cold exposure, compared with a decrease of 1.7 +/- 0.3 degrees C in the virgin rats. The tail skin temperature fell to 0 degrees C during cooling in all virgin rats and in pregnant rats at each gestational stage. 3. During cold exposure at 10 degrees C for 30 min, pre-0-day rats also showed significantly larger falls in Tco (1.8 +/- 0.6 degrees C) than virgin (0.4 +/- 0.2 degrees C), pre-1-week (0.8 +/- 0.3 degrees C), post-0-day (0.3 +/- 0.3 degrees C) or post-1-week rats (0.4 +/- 0.3 degrees C). Although body weights in pre-0-day rats were far larger than those in virgin rats, the increase in oxygen consumption per animal during cold exposure was 50% lower in pre-0-day rats (2.2 +/- 0.5 ml/min) than in virgin rats (5.3 +/- 0.3 ml/min). There was no difference in basal oxygen consumption per animal between the late pregnant and virgin rats. 4. Within 24 h after parturition, both the decrease of Tco and the increase of oxygen consumption during cold exposure returned to the values observed in virgin rats. 5. The present results demonstrate clearly that cold-induced thermogenesis is significantly suppressed in rats at a late stage of pregnancy.