Lissoni P, Cazzaniga M, Tancini G, Scardino E, Musci R, Barni S, Maffezzini M, Meroni T, Rocco F, Conti A, Maestroni G
Division of Radiation Oncology, San Gerardo Hospital, Monza, Milan, Italy.
Eur Urol. 1997;31(2):178-81. doi: 10.1159/000474446.
Experimental and preliminary clinical studies have suggested that the pineal hormone melatonin (MLT) may stimulate hormone receptor expression on both normal and cancer cells. Moreover, MLT has appeared to inhibit the growth of some cancer cell lines, including prostate cancer, either by exerting a direct cytostatic action, or by decreasing the endogenous production of some tumor growth factors, such as prolactin (PRL) and insulin-like growth factor-1 (IGF-1). On this basis, a study was carried out to evaluate the clinical efficacy of a neuroendocrine combination consisting of the LHRH analogue triptorelin plus MLT in metastatic prostate cancer progressing on triptorelin alone.
The study including 14 consecutive metastatic prostate cancer patients with poor clinical conditions (median age: 70.5 years; median PS: 50%), refractory or resistant to a previous therapy with the LHRH analogue triptorelin alone. Triptorelin was injected i.m. at 3.75 mg every 28 days, and MLT was given orally at 20 mg/day in the evening every day until progression, starting 7 days prior to triptorelin.
A decrease in PSA serum levels greater than 50% was obtained in 8/14 (57%) patients. Moreover, PSA mean concentrations significantly decreased on therapy of triptorelin plus MLT. In addition, a normalization of platelet number was obtained in 3/5 patients with persistent thrombocytopenia prior to study. Mean serum levels of both PRL and IGF-1 significantly decreased on therapy. Finally, a survival longer than 1 year was achieved in 9/14 (64%) patients. This preliminary study would suggest that the concomitant administration of the pineal hormone MLT may overcome the clinical resistance to LHRH analogues and improve the clinical conditions in metastatic prostatic cancer patients.
实验研究和初步临床研究表明，松果体激素褪黑素（MLT）可能刺激正常细胞和癌细胞上的激素受体表达。此外，MLT似乎通过发挥直接的细胞生长抑制作用，或通过降低某些肿瘤生长因子（如催乳素（PRL）和胰岛素样生长因子-1（IGF-1））的内源性产生，来抑制包括前列腺癌在内的某些癌细胞系的生长。在此基础上，开展了一项研究，以评估由促性腺激素释放激素（LHRH）类似物曲普瑞林加MLT组成的神经内分泌联合疗法对仅接受曲普瑞林治疗后病情进展的转移性前列腺癌的临床疗效。
该研究纳入了14例连续的临床状况较差的转移性前列腺癌患者（中位年龄：70.5岁；中位体能状态：50%），这些患者对先前仅使用LHRH类似物曲普瑞林的治疗难治或耐药。曲普瑞林每28天肌肉注射3.75 mg，MLT从曲普瑞林注射前7天开始，每天晚上口服20 mg/天，直至病情进展。
14例患者中有8例（57%）血清前列腺特异性抗原（PSA）水平下降超过50%。此外，曲普瑞林加MLT治疗期间PSA平均浓度显著降低。另外，研究前5例持续性血小板减少症患者中有3例血小板数量恢复正常。治疗期间PRL和IGF-1的平均血清水平均显著降低。最后，14例患者中有9例（64%）生存期超过1年。这项初步研究表明，松果体激素MLT的联合应用可能克服对LHRH类似物的临床耐药性，并改善转移性前列腺癌患者的临床状况。
