Lissoni Paolo, Rovelli Franco, Frassineti Andrea, Fumagalli Luca, Malysheva Ola, Conti Ario, Maestroni Georges
Division of Radiation Oncology, S.Gerardo Hospital, Monza (Milan), Italy. FAX +39 039 233 3414.
Neuro Endocrinol Lett. 2000;21(4):319-323.
The recent advances in psycho-neuro-endocrino-immunology have demonstrated the existence of several endogenous neuroendocrine substances, capable of affecting both tumor growth and host anticancer immune defenses. The pineal gland would represent one of the most important organs releasing antiproliferative and immunostimulating substances, the most known of them is melatonin (MLT). However, MLT would not be the only pineal indole provided by antitumor activity. Other pineal indoles, namely 5-methoxytryptamine (5-MTT), would play antitumor effects, by either inhibiting cancer cell proliferation or stimulating the anticancer immunity. Preliminary data have shown that MLT may deserve antitumor activity in the treatment of human neoplasms, whereas at present there are no clear data about 5-MTT. In an attempt to obtain some preliminary data about the anticancer properties of 5-MTT in humans, we have evaluated the efficacy of MLT plus 5-MTT in untreatable advanced cancer patients progressing on MLT alone. METHODS: The study included 73 untreatable advanced solid tumor patients, who had progressed after two months of MLT therapy alone. According to tumor histotype, patients were randomized to receive MLT alone (20 mg/day orally in the evening) or MLT plus 5-MTT (1 mg at noon orally), every day for at least two months. The clinical response was evaluated according to WHO criteria. RESULTS: A partial response (PR) occurred in two patients treated with MLT + 5-MTT and in none of the patients receiving MLT alone. A stable disease (SD) was achieved in only 2/37 patients on MLT therapy alone, and in 8/36 patients receiving MLT plus 5-MTT. Therefore, the percent of non-progressing patients (SD + PR) obtained with MLT plus 5-MTT was significantly higher than that obtained with MLT alone. Moreover, the relief of asthenia and depressant symptoms was significantly higher in patients concomitantly treated with 5-MTT. DISCUSSION: This preliminary study would suggest that the concomitant administration of the less known pineal indole 5-MTT, also provided by antiproliferative and immunomodulating effects, may further amplify the oncostatic activity of the pineal hormone MLT in the palliative and curative therapy of advanced untreatable human solid neoplasms.
心理神经内分泌免疫学的最新进展表明，存在几种内源性神经内分泌物质，它们能够影响肿瘤生长和宿主的抗癌免疫防御。松果体可能是释放抗增殖和免疫刺激物质的最重要器官之一，其中最知名的是褪黑素（MLT）。然而，MLT并非唯一具有抗肿瘤活性的松果体吲哚。其他松果体吲哚，即5-甲氧基色胺（5-MTT），可通过抑制癌细胞增殖或刺激抗癌免疫发挥抗肿瘤作用。初步数据表明，MLT在人类肿瘤治疗中可能具有抗肿瘤活性，而目前关于5-MTT尚无明确数据。为了获得一些关于5-MTT在人类抗癌特性的初步数据，我们评估了MLT加5-MTT对仅接受MLT治疗但病情进展的不可治疗的晚期癌症患者的疗效。方法：该研究纳入了73例不可治疗的晚期实体瘤患者，这些患者在仅接受两个月的MLT治疗后病情进展。根据肿瘤组织类型，患者被随机分为两组，一组单独接受MLT（每晚口服20mg/天），另一组接受MLT加5-MTT（中午口服1mg），每天治疗至少两个月。根据世界卫生组织标准评估临床反应。结果：接受MLT + 5-MTT治疗的两名患者出现部分缓解（PR），而单独接受MLT治疗的患者无一出现部分缓解。仅接受MLT治疗的37例患者中只有2例病情稳定（SD），接受MLT加5-MTT治疗的36例患者中有8例病情稳定。因此，MLT加5-MTT治疗获得的病情无进展患者（SD + PR）百分比显著高于单独使用MLT治疗的患者。此外，同时接受5-MTT治疗的患者乏力和抑郁症状的缓解程度明显更高。讨论：这项初步研究表明，同时给予较少为人所知的松果体吲哚5-MTT（其也具有抗增殖和免疫调节作用），可能会进一步增强松果体激素MLT在晚期不可治疗的人类实体瘤姑息和治愈治疗中的抑癌活性。
