Hercbergs Aleck, Johnson Rebecca E, Ashur-Fabian Osnat, Garfield David H, Davis Paul J
Departments of Radiation Oncology and Neuroradiology, Cleveland Clinic, Cleveland, Ohio, USA; Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel; University of Colorado Cancer Center, Aurora, Colorado, USA; ProMed Cancer Centers, Shanghai, People's Republic of China; Department of Medicine, Albany Medical College, Albany, New York, USA; The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, New York, USA
Departments of Radiation Oncology and Neuroradiology, Cleveland Clinic, Cleveland, Ohio, USA; Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel; University of Colorado Cancer Center, Aurora, Colorado, USA; ProMed Cancer Centers, Shanghai, People's Republic of China; Department of Medicine, Albany Medical College, Albany, New York, USA; The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, New York, USA.
Oncologist. 2015 Jan;20(1):72-6. doi: 10.1634/theoncologist.2014-0308. Epub 2014 Nov 19.
Clinical studies have shown that interventional lowering of serum free thyroxine (FT4) may be associated with extended survival in patients with some terminal cancers. The report of success with this approach in glioblastoma multiforme caused involvement of the author (A.H.) in the prospective consultative management of 23 end-stage solid tumor patients in whom hypothyroxinemia was induced to prolong life.
Patients were self-referred or recommended by attending physicians to the author (A.H.) and had advanced cancers of the brain, ovary, lung, pancreas, salivary gland, and breast or had mesothelioma or soft-tissue sarcoma. Hypothyroxinemia was achieved in euthyroid patients by using methimazole, with the addition of 3,3',5-triiodo-L-thyronine (L-T3) to prevent hypothyroidism and suppress endogenous thyrotropin (TSH). In patients with pre-existent primary hypothyroidism, T3 administration was substituted for T4 replacement. Serum FT4 and TSH concentrations were serially monitored to enable adjustments to drug therapy and prevent clinical hypothyroidism. Survival was measured from the date of hypothyroxinemia induction with T3 or methimazole plus T3. Outcomes were compared with the odds of death based on the Surveillance Epidemiology and End Results and American Joint Committee on Cancer databases and literature reports.
The survival time of 83% (19 of 23) of patients exceeded the 20% expected 1-year survival for this hypothyroxinemic, end-stage cancer group. The difference between actual and expected survival was significant.
Although this is an uncontrolled observational experience with frank limitations, compassionate medical induction of hypothyroxinemia should be considered for patients with advanced cancers to whom other avenues of treatment are closed.
临床研究表明,对血清游离甲状腺素(FT4)进行干预性降低可能与某些晚期癌症患者的生存期延长有关。多形性胶质母细胞瘤采用这种方法取得成功的报告,促使作者(A.H.)参与了23例晚期实体瘤患者的前瞻性咨询管理,这些患者通过诱发甲状腺功能减退来延长生命。
患者由本人转诊或经主治医生推荐给作者(A.H.),患有脑、卵巢、肺、胰腺、唾液腺和乳腺癌的晚期癌症,或患有间皮瘤或软组织肉瘤。通过使用甲巯咪唑使甲状腺功能正常的患者出现甲状腺功能减退,同时添加3,3',5-三碘-L-甲状腺原氨酸(L-T3)以预防甲状腺功能减退并抑制内源性促甲状腺激素(TSH)。对于已存在原发性甲状腺功能减退的患者,用T3替代T4替代治疗。连续监测血清FT4和TSH浓度,以便调整药物治疗并预防临床甲状腺功能减退。生存期从使用T3或甲巯咪唑加T3诱发甲状腺功能减退之日起计算。根据监测、流行病学和最终结果以及美国癌症联合委员会数据库和文献报告,将结果与死亡几率进行比较。
83%(23例中的l9例)患者的生存时间超过了该甲状腺功能减退的晚期癌症组预期1年生存率的20%。实际生存与预期生存之间的差异具有显著性。
尽管这是一项存在明显局限性的非对照观察性经验,但对于其他治疗途径均已用尽的晚期癌症患者,应考虑出于同情进行医学诱导甲状腺功能减退。