Tisman Glenn, Garcia April
Whittier Cancer Research Building, 13025 Bailey Street, Whittier, CA 90601, USA.
J Med Case Rep. 2011 Aug 25;5:413. doi: 10.1186/1752-1947-5-413.
This is the first report of possible direct stimulation of hormone-resistant prostate cancer or interference of docetaxel cytotoxicity of prostate cancer in a patient with biochemical relapse of prostatic-specific antigen. This observation is of clinical and metabolic importance, especially at a time when more than 80 countries have fortified food supplies with folic acid and some contemplate further fortification with vitamin B12.
Our patient is a 71-year-old Caucasian man who had been diagnosed in 1997 with prostate cancer, stage T1c, and Gleason score 3+4 = 7. His primary treatment included intermittent androgen deprivation therapy including leuprolide + bicalutamide + deutasteride, ketoconazole + hydrocortisone, nilandrone and flutamide to resistance defined as biochemical relapse of PSA. While undergoing docetaxel therapy to treat a continually increasing prostate-specific antigen level, withdrawal of 10 daily doses of a supplement containing 500 μg of vitamin B12 as cyanocobalamin, as well as 400 μg of folic acid as pteroylglutamic acid and 400 μg of L-5-methyltetrahydrofolate for a combined total of 800 μg of mixed folates, was associated with a return to a normal serum prostatic-specific antigen level.
This case report illustrates the importance of the effects of supplements containing large amounts of folic acid, L-5-methyltetrahydrofolate, and cyanocobalamin on the metabolism of prostate cancer cells directly and/or B vitamin interference with docetaxel efficacy. Physicians caring for patients with prostate cancer undergoing watchful waiting, hormone therapy, and/or chemotherapy should consider the possible acceleration of tumor growth and/or metastasis and the development of drug resistance associated with supplement ingestion. We describe several pathways of metabolic and epigenetic interactions that could affect the observed changes in serum levels of prostate-specific antigen.
这是关于一名前列腺特异性抗原生化复发患者中可能直接刺激激素抵抗性前列腺癌或干扰多西他赛对前列腺癌细胞毒性作用的首例报告。这一观察结果具有临床和代谢方面的重要意义,尤其是在超过80个国家已在食品供应中强化添加叶酸且一些国家考虑进一步强化添加维生素B12的当下。
我们的患者是一名71岁的白种男性,于1997年被诊断为前列腺癌,T1c期, Gleason评分3 + 4 = 7。他的初始治疗包括间歇性雄激素剥夺疗法,使用亮丙瑞林 + 比卡鲁胺 + 度他雄胺、酮康唑 + 氢化可的松、尼鲁米特和氟他胺,直至出现定义为PSA生化复发的耐药情况。在接受多西他赛治疗以应对持续升高的前列腺特异性抗原水平时,停用了每日10剂含有500μg氰钴胺形式维生素B12、400μg蝶酰谷氨酸形式叶酸以及400μg L - 5 - 甲基四氢叶酸(混合叶酸总量为800μg)的补充剂,随后血清前列腺特异性抗原水平恢复正常。
本病例报告说明了含有大量叶酸、L - 5 - 甲基四氢叶酸和氰钴胺的补充剂对前列腺癌细胞代谢的直接影响以及/或者B族维生素对多西他赛疗效的干扰的重要性。照料接受观察等待、激素治疗和/或化疗的前列腺癌患者的医生应考虑补充剂摄入可能加速肿瘤生长和/或转移以及产生耐药性的情况。我们描述了几种可能影响观察到的前列腺特异性抗原血清水平变化的代谢和表观遗传相互作用途径。