Santini Daniele, Vincenzi Bruno, Massacesi Cristian, Picardi Antonio, Gentilucci Umberto Vespasiani, Esposito Vincenzo, Liuzzi Giuseppina, La Cesa Annalisa, Rocci Laura, Marcucci Fabiana, Montesarchio Vincenzo, Groeger Angela M, Bonsignori Maurizio, Tonini Giuseppe
Medical Oncology, Center for Biomedical Research (CIR), Laboratory of Internal Medicine and Hepatology, Campus Bio-Medico University, Rome, Italy.
Anticancer Res. 2003 Nov-Dec;23(6D):5173-9.
Liver toxicity can be observed during treatment with most chemotherapic agents, and represents one of the principal causes of dose reduction or chemotherapy delays. S-Adenosylmethionine (AdoMet) plays a critical role in the synthesis of polyamines and provides cysteine for the production of glutathione (GSH), the major endogenous hepatoprotective agent. Our study was aimed at assessing the protective effect of AdoMet supplementation in cancer chemotherapy-induced liver toxicity.
Fifty cancer patients who developed, for the first time, anticancer chemotherapy-induced liver toxicity were studied. Enrolled patients received oral AdoMet supplementation.
AST, ALT and LDH levels recorded at the moment of the recognition of liver toxicity were significantly reduced after one week of AdoMet therapy (respectively p: 0.009, 0.0005 and 0.012). AST, ALT and LDH decrease was confirmed after two weeks of treatment. Furthermore, the effect on these enzyme levels persisted in the following chemotherapy courses, permitting our patients to perform the scheduled chemotherapy courses with a minimal number of dose reductions or administration delays. The efficacy of AdoMet supplementation was not influenced by the presence of liver metastases, and no appreciable side-effects were recognized.
The results of our study clearly demonstrate a protective effect of AdoMet in cancer chemotherapy-induced liver toxicity. Further large phase III studies are required to assess the real clinical benefit associated with AdoMet supplementation.
在大多数化疗药物治疗期间均可观察到肝毒性，这是导致剂量减少或化疗延迟的主要原因之一。S-腺苷甲硫氨酸（AdoMet）在多胺合成中起关键作用，并为谷胱甘肽（GSH，主要的内源性肝脏保护剂）的产生提供半胱氨酸。我们的研究旨在评估补充AdoMet对癌症化疗所致肝毒性的保护作用。
对首次发生抗癌化疗所致肝毒性的50例癌症患者进行了研究。入选患者接受口服AdoMet补充治疗。
在认识到肝毒性时记录的AST、ALT和LDH水平在AdoMet治疗1周后显著降低（分别为p：0.009、0.0005和0.012）。治疗2周后，AST、ALT和LDH的降低得到证实。此外，在随后的化疗疗程中，对这些酶水平的影响持续存在，使我们的患者能够以最少的剂量减少或给药延迟完成预定的化疗疗程。补充AdoMet的疗效不受肝转移的影响，且未发现明显的副作用。
我们的研究结果清楚地证明了AdoMet对癌症化疗所致肝毒性具有保护作用。需要进一步进行大规模的III期研究来评估补充AdoMet的实际临床益处。
