外源性褪黑素对肿瘤辅助治疗效果的Meta分析_《中国循证医学杂志》

作者：

 徐维平 ¹ , 王伟迪 ¹ , 徐婷娟 ¹ , 魏伟 ² , 孙志刚 ³ , 胡世莲 ¹ , 严光 ¹

1. 安徽省立医院（合肥?230001）；2. 安徽医科大学临床药理研究所（合肥?230032）；3. 河北省石家庄市第六医院（石家庄?050051）;

关键词：

褪黑素肿瘤辅助治疗 Meta分析系统评价

DOI：

10.7507/1672-2531.20110119

视频：

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摘要 全文 图表 视频 参考文献 施引文献 补充材料

目的　系统评价肿瘤患者进行化疗或放疗时，采用褪黑素进行辅助治疗的有效性和安全性。
方法　计算机检索MEDLINE（1980～2010.1）、Cochrane图书馆（2009年第4期）、万方数据库（1980～2010.1）、VIP（1980～2010.1）、CNKI（1980～2010.1）、ELSEVIER ScienceDirect（SDOS）（1980～2010.1）、Nature（1980～2010.1）以及在研临床试验数据库（www.clinicaltrials.gov和www.controlled-trials.com），纳入研究外源性褪黑素辅助治疗肿瘤效果的随机对照试验，由两位研究者进行资料提取和质量评价后，采用Stata 10.1软件进行Meta分析。
结果　共纳入8个RCT。Meta分析结果显示：褪黑素能显著提高肿瘤患者的疾病缓解率［RR=1.98，95% CI（1.52，2.58）］及1年生存率［RR=1.90，95%CI（1.28，2.83）］，同时能显著减轻化疗或放疗对骨髓抑制的毒性作用［RR=0.12，95%CI（0.06，0.27）］；治疗期间未见褪黑素相关不良反应的报道。
结论　当前证据显示，褪黑素作为肿瘤的辅助治疗药物，对提高患者疾病缓解率、减轻化疗放疗的毒性、延长患者的寿命具有一定作用。受纳入研究质量限制，上述结论尚需开展更多高质量研究验证。

引用本文： 徐维平,王伟迪,徐婷娟,魏伟,孙志刚,胡世莲,严光. 外源性褪黑素对肿瘤辅助治疗效果的Meta分析. 中国循证医学杂志, 2011, 11(6): 681-686. doi: 10.7507/1672-2531.20110119 复制

1.	1 Blask DE. Melatonin, sleep disturbance and cancer risk. Sleep Med Rev , 2009, 13(4): 257-264.
2.	Pacchierotti C, Iapichino S, Bossini L, et al . Melatonin in psychiatric disorders: a review on the melatonin involvement in psychiatry. Front Neuroendocrinol , 2001, 22(1): 18-32.
3.	de Castro-Silva C, de Bruin VM, Cunha GM, et al . Melatonin improves sleep and reduces nitrite in the exhaled breath condensate in cystic fibrosis--a randomized, double-blind placebo-controlled study. J Pineal Res , 2010, 48(1): 65-71.
4.	Sainz RM, Reiter RJ, Tan DX, et al . Critical role of glutathione in melatonin enhancement of tumor necrosis factor and ionizing radiation-induced apoptosis in prostate cancer cells in vitro. J Pineal Res , 2008, 45(3): 258-270.
5.	Korkmaz A, Tamura H, Manchester LC, et al . Combination of melatonin and a peroxisome proliferator-activated receptor-gamma agonist induces apoptosis in a breast cancer cell line. J Pineal Res , 2009, 46(1): 115-116.
6.	Pizarro JG, Yeste-Velasco M, Esparza JL, et al . The antiproliferative activity of melatonin in B65 rat dopaminergic neuroblastoma cells is related to the downregulation of cell cycle-related genes. J Pineal Res , 2008, 45(1): 8-16.
7.	Leon-Blanco MM, Guerrero JM, Reiter RJ, et al . Melatonin inhibits telomerase activity in the MCF-7 tumor cell line both in vivo and in vitro. J Pineal Res , 2003, 35(3): 204-11.
8.	Dauchy RT, Blask DE, Dauchy EM, et al . Antineoplastic effects of melatonin on a rare malignancy of mesenchymal origin: melatonin receptor-mediated inhibition of signal transduction, linoleic acid metabolism and growth in tissue-isolated human leiomyosarcoma xenografts. J Pineal Res , 2009, 47(1): 32-42.
9.	D. Moher, A. Liberati, J. Tetzlaff, et al . Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. Journal of Clinical Epidemiology , 2009, 62(10): 1006-1012.
10.	Jadad AR, Moore RA, Carroll D, et al . Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials , 1996, 17(1): 1-12.
11.	Lissoni P, Barni S, Mandalà M, et al . Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status. Eur J Cancer , 1999, 35(12): 1688-1692.
12.	Lissoni P, Tancini G, Barni S, et al . Treatment of cancer chemotherapy-induced toxicity with the pineal hormone melatonin. Support Care Cancer , 1997, 5(2): 126-129.
13.	Lissoni P, Chilelli M, Villa S, et al . Five years survival in metastatic non-small cell lung cancer patients treated with chemotherapy alone or chemotherapy and melatonin: a randomized trial. J Pineal Res , 2003, 35(1): 12-15.
14.	晏建军, 沈锋, 王葵, 等. 褪黑素对中晚期肝癌肝动脉化疗栓塞的协同和保护作用. 第二军医大学学报, 2001, 22(9): 858-861.
15.	Lissoni P, Paolorossi F, Ardizzoia A, et al . A randomized study of chemotherapy with cisplatin plus etoposide versus chemoendocrine therapy with cisplatin, etoposide and the pineal hormone melatonin as a first-line treatment of advanced non-small cell lung cancer patients in a poor clinical state. J Pineal Res , 1997, 23(1): 15-19.
16.	Lissoni P. Biochemotherapy with immunomodulating pineal hormones other than melatonin: 5-methoxytryptamine as a new oncostatic pineal agent. Pathol Biol (Paris) , 2007, 55(3-4): 198-200.
17.	Lissoni P, Meregalli S, Nosetto L, et al . Increased survival time in brain glioblastomas by a radioneuroendocrine strategy with radiotherapy plus melatonin compared to radiotherapy alone. Oncology , 1996, 53(1): 43-46.
18.	Cerea G, Vaghi M, Ardizzoia A, et al . Biomodulation of cancer chemotherapy for metastatic colorectal cancer: a randomized study of weekly low-dose irinotecan alone versus irinotecan plus the oncostatic pineal hormone melatonin in metastatic colorectal cancer patients progressing on 5-fluorouracil-containing combinations. Anticancer Res , 2003, 23(2C): 1951-1954.
19.	Cucina A, Proietti S, D'Anselmi F, et al . Evidence for a biphasic apoptotic pathway induced by melatonin in MCF-7 breast cancer cells. J Pineal Res , 2009, 46(2): 172-180.
20.	Joo SS, Yoo YM. Melatonin induces apoptotic death in LNCaP cells via p38 and JNK pathways: therapeutic implications for prostate cancer. J Pineal Res , 2009, 47(1): 8-14.
21.	Watanabe M, Kobayashi Y, Takahashi N, et al . Expression of melatonin receptor (MT1) and interaction between melatonin and estrogen in endometrial cancer cell line. J Obstet Gynaecol Res , 2008, 34(4): 567-573.
22.	Martín-Renedo J, Mauriz JL, Jorquera F, et al . Melatonin induces cell cycle arrest and apoptosis in hepatocarcinoma HepG2 cell line. J Pineal Res , 2008, 45(4): 532-540.
23.	Lissoni P, Barni S, Ardizzoia A, et al . A randomized study with the pineal hormone melatonin versus supportive care alone in patients with brain metastases due to solid neoplasms. Cancer , 1994, 73(3): 699-701.
24.	蒋旭琴, 韩志君, 梅晓冬. 褪黑素对免疫系统的调节作用及其应用研究进展. 细胞与分子免疫学杂志, 2007, 23(11): 1091-1093.
25.	Mills E, Wu P, Seely D, et al . Melatonin in the treatment of cancer: a systematic review of randomized controlled trials and meta-analysis. J Pineal Res , 2005, 39(4): 360-366.

1. 1 Blask DE. Melatonin, sleep disturbance and cancer risk. Sleep Med Rev , 2009, 13(4): 257-264.
2. Pacchierotti C, Iapichino S, Bossini L, et al . Melatonin in psychiatric disorders: a review on the melatonin involvement in psychiatry. Front Neuroendocrinol , 2001, 22(1): 18-32.
3. de Castro-Silva C, de Bruin VM, Cunha GM, et al . Melatonin improves sleep and reduces nitrite in the exhaled breath condensate in cystic fibrosis--a randomized, double-blind placebo-controlled study. J Pineal Res , 2010, 48(1): 65-71.
4. Sainz RM, Reiter RJ, Tan DX, et al . Critical role of glutathione in melatonin enhancement of tumor necrosis factor and ionizing radiation-induced apoptosis in prostate cancer cells in vitro. J Pineal Res , 2008, 45(3): 258-270.
5. Korkmaz A, Tamura H, Manchester LC, et al . Combination of melatonin and a peroxisome proliferator-activated receptor-gamma agonist induces apoptosis in a breast cancer cell line. J Pineal Res , 2009, 46(1): 115-116.
6. Pizarro JG, Yeste-Velasco M, Esparza JL, et al . The antiproliferative activity of melatonin in B65 rat dopaminergic neuroblastoma cells is related to the downregulation of cell cycle-related genes. J Pineal Res , 2008, 45(1): 8-16.
7. Leon-Blanco MM, Guerrero JM, Reiter RJ, et al . Melatonin inhibits telomerase activity in the MCF-7 tumor cell line both in vivo and in vitro. J Pineal Res , 2003, 35(3): 204-11.
8. Dauchy RT, Blask DE, Dauchy EM, et al . Antineoplastic effects of melatonin on a rare malignancy of mesenchymal origin: melatonin receptor-mediated inhibition of signal transduction, linoleic acid metabolism and growth in tissue-isolated human leiomyosarcoma xenografts. J Pineal Res , 2009, 47(1): 32-42.
9. D. Moher, A. Liberati, J. Tetzlaff, et al . Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. Journal of Clinical Epidemiology , 2009, 62(10): 1006-1012.
10. Jadad AR, Moore RA, Carroll D, et al . Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials , 1996, 17(1): 1-12.
11. Lissoni P, Barni S, Mandalà M, et al . Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status. Eur J Cancer , 1999, 35(12): 1688-1692.
12. Lissoni P, Tancini G, Barni S, et al . Treatment of cancer chemotherapy-induced toxicity with the pineal hormone melatonin. Support Care Cancer , 1997, 5(2): 126-129.
13. Lissoni P, Chilelli M, Villa S, et al . Five years survival in metastatic non-small cell lung cancer patients treated with chemotherapy alone or chemotherapy and melatonin: a randomized trial. J Pineal Res , 2003, 35(1): 12-15.
14. 晏建军, 沈锋, 王葵, 等. 褪黑素对中晚期肝癌肝动脉化疗栓塞的协同和保护作用. 第二军医大学学报, 2001, 22(9): 858-861.
15. Lissoni P, Paolorossi F, Ardizzoia A, et al . A randomized study of chemotherapy with cisplatin plus etoposide versus chemoendocrine therapy with cisplatin, etoposide and the pineal hormone melatonin as a first-line treatment of advanced non-small cell lung cancer patients in a poor clinical state. J Pineal Res , 1997, 23(1): 15-19.
16. Lissoni P. Biochemotherapy with immunomodulating pineal hormones other than melatonin: 5-methoxytryptamine as a new oncostatic pineal agent. Pathol Biol (Paris) , 2007, 55(3-4): 198-200.
17. Lissoni P, Meregalli S, Nosetto L, et al . Increased survival time in brain glioblastomas by a radioneuroendocrine strategy with radiotherapy plus melatonin compared to radiotherapy alone. Oncology , 1996, 53(1): 43-46.
18. Cerea G, Vaghi M, Ardizzoia A, et al . Biomodulation of cancer chemotherapy for metastatic colorectal cancer: a randomized study of weekly low-dose irinotecan alone versus irinotecan plus the oncostatic pineal hormone melatonin in metastatic colorectal cancer patients progressing on 5-fluorouracil-containing combinations. Anticancer Res , 2003, 23(2C): 1951-1954.
19. Cucina A, Proietti S, D'Anselmi F, et al . Evidence for a biphasic apoptotic pathway induced by melatonin in MCF-7 breast cancer cells. J Pineal Res , 2009, 46(2): 172-180.
20. Joo SS, Yoo YM. Melatonin induces apoptotic death in LNCaP cells via p38 and JNK pathways: therapeutic implications for prostate cancer. J Pineal Res , 2009, 47(1): 8-14.
21. Watanabe M, Kobayashi Y, Takahashi N, et al . Expression of melatonin receptor (MT1) and interaction between melatonin and estrogen in endometrial cancer cell line. J Obstet Gynaecol Res , 2008, 34(4): 567-573.
22. Martín-Renedo J, Mauriz JL, Jorquera F, et al . Melatonin induces cell cycle arrest and apoptosis in hepatocarcinoma HepG2 cell line. J Pineal Res , 2008, 45(4): 532-540.
23. Lissoni P, Barni S, Ardizzoia A, et al . A randomized study with the pineal hormone melatonin versus supportive care alone in patients with brain metastases due to solid neoplasms. Cancer , 1994, 73(3): 699-701.
24. 蒋旭琴, 韩志君, 梅晓冬. 褪黑素对免疫系统的调节作用及其应用研究进展. 细胞与分子免疫学杂志, 2007, 23(11): 1091-1093.
25. Mills E, Wu P, Seely D, et al . Melatonin in the treatment of cancer: a systematic review of randomized controlled trials and meta-analysis. J Pineal Res , 2005, 39(4): 360-366.

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外源性褪黑素对肿瘤辅助治疗效果的Meta分析

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《中国循证医学杂志》

外源性褪黑素对肿瘤辅助治疗效果的Meta分析

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