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

Abstract

e15030 Background: Management of advanced prostate cancer with relapse after initial hormonal therapy is still challenging. Some reports have shown that the second line maximum androgen blockade with an alternative antiandrogen (2nd MAB) is still effective. However 2nd MAB has relatively low PSA response rate of about 35%. We sought to determine whether the combination therapy of 2nd MAB and UFT would be even more effective than 2nd MAB alone and also to correlate the treatment effect with the thymidylate synthase (TS) mRNA expression levels. Methods: Patients who were histologically confirmed with prostate cancer and relapsed after LH-RH analogue alone or MAB were included in this study. ECOG performance status was 0-2. All patients were randomly allocated into two groups, 2nd MAB (group A) or 2nd MAB combined with UFT orally at a dose of 260 mg/m2/day (group B) until recurrence. The primary endpoint was PSA response rate (effectiveness defined as > 50% decrease of PSA) and one of the secondary endpoint was PFS. TS mRNA expression levels in formalin fixed paraffin embedded biopsy specimens were measured by RT-PCR method. Results: Fifty three patients were enrolled in this study and clinical data for 38 patients were available so far. Median age was 76 (47-89) years. There were no severe AEs in both groups. PSA response rate in group B (70.6%) tended to be higher than that in group A (36.8%) (p=0.0543). Group B (16.1 months) had significantly longer median PFS than group A (6.4 months) (p=0.0028). Biopsy samples were available in 33 patients for TS mRNA measurement. Interestingly, among patients who were treated with 2nd MAB combined with UFT, those with low TS (88%) had higher PSA response rate than those with high TS (57%). Conclusions: After relapse with initial hormonal therapy, 2nd MAB along with UFT is an effective and well-tolerated treatment option before introducing docetaxel, especially for elderly patients with prostate cancer with low TS expression level. No significant financial relationships to disclose.