A multicenter, randomized phase II study of the second-line maximum androgen blockade with an alternative antiandrogen combined with tegafur-uracil (UFT) for prostate cancer with relapse after initial hormonal therapy.

Abstract

4624 Background: Some reports have shown that the second-line maximum androgen blockade with an alternative antiandrogen (2nd MAB) is still effective. However 2ndMAB has relatively low PSA response rate. We sought to determine whether the combination therapy of 2nd MAB and UFT would be even more effective and to correlate the treatment efficacy with mRNA expressions of the enzymes that are related to 5-FU metabolism. Methods: Patients who were histologically confirmed with prostate cancer and who relapsed after initial hormonal therapy were included in this study. All patients were randomly allocated into two groups, 2nd MAB (group A) or 2nd MAB combined with UFT (group B). mRNA expressions of four enzymes including thymidylate synthase (TS), dihydropyrimidine dehydrogenase, orotate phosphoribosyl transferase, thymidine phosphorylase in prostate cancer cells obtained by laser capture microdissection were measured by real time RT-PCR. The primary endpoint was PSA response rate as defined as ≥ 50% decrease from the baseline. The secondary endpoints included progression-free survival (PFS), adverse events (AEs) and the correlation of treatment efficacy with mRNA expressions of the four enzymes. Results: Fifty two patients were enrolled in this study. Median age was 77 (47-92) years old. PSA response rate in group B (61.5%) tended to be higher than that in group A (34.6%) (p=0.095). The median percent PSA changes from baseline at 12 weeks were -8.4% in group A and -70.2% in group B. Group B (15.9 months) had significantly longer median PFS than group A (6.4 months) (p=0.0137). Prostate biopsy specimens were available in 49 patients for mRNA measurement. In group B, those with low TS (81.8%) tended to have higher PSA response rate than those with high TS (46.2%). In addition, among the patients with low TS, group B had significantly longer PFS than group A (p=0.0175). There were no severe AEs in both groups. Conclusions: After relapse with initial hormonal therapy, an alternative antiandrogen (2nd MAB) along with UFT is an effective and well-tolerated treatment option.