Upfront Docetaxel with LH-RH Antagonist for Metastatic Hormone Sensitive Prostate Cancer Considering Epithelial to Mesenchymal Transition

Abstract

Objective: Upfront docetaxel use for hormone na ï ve advanced prostate cancer is reported that it successfully delayed the progression to hormone refractory stage, though the adequate methodology to obtain the maximum effect is unclear. We investigated these issues from our experiences of upfront docetaxel use with LH-RH antagonist for metastatic hormone sensitive prostate cancer, aiming at the prevention of epithelial-mesenchymal transition (EMT) for apoptosis tolerance. Patients and Methods: Of 31 stage IV new prostate cancer patients treated with upfront docetaxel and LH-RH antagonist (Degarelix), 25 patients who could be followed more than 12 months (mean 36.2 months) were analyzed. Docetaxel was used two to three courses basically 75 mg/m2 dose initializing two weeks after the induction of first Degarelix. Results: The clinical course was divided clearly to two groups according to prostate specific antigen (PSA) values. Of 25 patients, 12 patient’s PSA did not decrease below 0.1 ng/ml within 6 months (group A) and gradually rose afterwards. PSA in another 13 patients (group B) decreased below 0.1 within 6 months and kept below 0.1 during the follow up period. Although statistically not significant, the initial group A’s PSA was higher than group B’s (average 1308 and 353 ng/ml), however, number of metastasis, Gleason sum, and bone metastatic extent of disease showed no difference between them. Among group B patients, 7 cases had only upfront docetaxel and hormonal therapy, and some of these patients showed only atrophic gland and fibrotic tissue at second prostate biopsy (specimens after more than two years of therapy), suggesting complete response. Conclusion: Our study suggested that PSA value at 6 months may predict the outcome of whole therapy. Patients showing PSA less than 0.1 ng/ml at 6 months and requiring no therapy other than docetaxel and hormone may be induced to complete response. Upfront docetaxel with LH-RH antagonist may prevent EMT for obtaining apoptosis tolerance, in case the patient does not have the castration-resistant clone at the beginning of the therapy (group B).