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SUMMARYAR can be detected in HCC and the AR status might be a prognostic parameter that provides additional predictive information on survival, therefore hormonal manipulation has been the basis of a number of trials directed at HCC. On this basis, we conducted a phase II clinical trial to investigate the role of LHRH therapy in patients with unresectable HCC.This study aimed to evaluate the efficacy of LHRH agonist at a dose of 11.25 mg I.M. injection in HCC patients, detect androgen receptor status in malignant liver tissues and its relation to response to hormonal therapy. Fifty male patients with unresectable hepatocellular carcinoma were included in this study and all patients were subjected to history and clinical examination, routine laboratory investigations, radiological studies and special investigations to asses serum testosterone level before and after treatment, androgen receptor status by immunohistochemistry before treatment.Assessment of androgen receptor status by immunohistochemistry revealed AR+ve tumors in 16 patients (32%), andAR-ve tumors in 34 patients (68%).Leuprolide acetate 11.25mg is a potent agonist analogue of LHRH which, when chronically administered, inhibits gonadotropin secretion and suppresses of ovarian and testicular steroiodogenesis. Its effect on tumoral growth in 50 male patients with unresectable hepatocellular carcinoma was studied and showed stationary disease in 43 patients (86%), and progressive disease in 7 patients (14%), but none of the patients actually achieved at least partial response to treatment, none the less complete response. The drug was generally well tolerated, no serious side effects or toxic deaths occurred.There were no significant changes in AFP level or tumor size (before& after treatment) for either patient groups (AR+ve & AR-ve), while there was a significant reduction in the testosterone level after treatment compared to that before treatment, and that was evident in both AR +ve& -ve patients.The 1-year overall survival for all patients was 43% and median survival was 11 month. The 1-year over Survival for patients with AR –ve (47%) was higher than that for AR+ve patients (42%); however, not statistically significant (p=0.079).Both Child’s-Pugh class & performance status had a significant impact on survival; 1-year over survival for patients with Child’s-Pugh A (48%), had a significantly superior survival than those with Child’s-Pugh B (33%) (P=0.0001); and the 1-year over survival for patients with performance status 1, 2, 3 were (58%, 48%, 0 %, respectively) (p=0.001).CONCLUSIONTheoretically, anti-androgen therapy may be an attractive approach to patients with HCC; however, this may not be the case on the ground of reality as only 32% of our patients had AR +ve tumors; although there was a significant reduction in the testosterone level in response to leuprolide acetate, none of the patients achieved subjective regression in tumor size; and a substantial number of patients in whom stable disease was achieved had AR –ve tumors.Faced with the lack of curative therapeutic options for patients with advanced HCC, we can not conclude that anti-androgen therapy is of no benefit at all as 86% of the patients had a stable disease; but whether this stability could be attributed to anti-androgen therapy or to the relatively slow growth rate of the tumor will need a longer follow up of our patients and further studies on a larger scale of patients as well.Owing to the heterogeneous nature of HCC and the diversity of etiologic agents responsible for its occurrence, what may work for one patient may not work for another. So, we hope that the future studies directed to the better understanding of the molecular biology of HCC may identify the key molecular event(s) responsible for the initiation and/or progression of the disease; thus allowing treatment to be tailored on individual basis.
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