Simms M S, Scholfield D P, Jacobs E, Michaeli D, Broome P, Humphreys J E, Bishop M C
Department of Urology, City Hospital, Nottingham, UK.
Br J Cancer. 2000 Aug;83(4):443-6. doi: 10.1054/bjoc.2000.1315.
D17DT consists of the GnRH decapeptide linked to diphtheria toxoid. The aim of this pilot study was to assess the tolerance of D17DT and the production of anti-GnRH antibodies from two doses, 30 and 100 microg, in patients with locally advanced prostate cancer. Twelve patients with histologically proven prostate cancer in whom hormonal therapy was indicated were recruited. Patients received either 30 or 100 microg given intramuscularly on three separate occasions over six weeks. Patients were followed up and blood was taken for estimation of serum testosterone, PSA and anti-GnRH antibody titre. Overall the drug was well tolerated. In 5 patients a significant reduction in serum testosterone and PSA was seen. Castrate levels of testosterone were achieved in 4 and maintained for up to 9 months. Patients with the highest antibody titre had the best response in terms of testosterone suppression. This study shows that it is possible to immunize a patient with prostate cancer against GnRH to induce castrate levels of testosterone. This state appears to be reversible. This novel form of immunotherapy may have advantages over conventional forms of hormonal therapy and further studies are warranted in order to try and increase the proportion of responders.
D17DT由与白喉类毒素相连的促性腺激素释放激素（GnRH）十肽组成。这项初步研究的目的是评估局部晚期前列腺癌患者对D17DT的耐受性以及30微克和100微克两种剂量的D17DT所诱导的抗GnRH抗体的产生情况。招募了12名经组织学证实患有前列腺癌且需要进行激素治疗的患者。患者在六周内分三次接受30微克或100微克的肌肉注射。对患者进行随访，并采集血液以评估血清睾酮、前列腺特异性抗原（PSA）和抗GnRH抗体滴度。总体而言，该药物耐受性良好。5名患者的血清睾酮和PSA显著降低。4名患者达到了去势水平的睾酮，并维持了长达9个月。抗体滴度最高的患者在睾酮抑制方面反应最佳。这项研究表明，对前列腺癌患者进行GnRH免疫接种以诱导去势水平的睾酮是可行的。这种状态似乎是可逆的。这种新型免疫疗法可能比传统激素疗法具有优势，有必要进行进一步研究以尝试提高反应者的比例。
