Medically induced euthyroid hypothyroxinemia may extend survival in compassionate need cancer patients: an observational study

Our plain-English summary of Medically induced euthyroid hypothyroxinemia may extend survival in compassionate need cancer patients: an observational study, by A. Hercbergs, R.E. Johnson, O. Ashur-Fabian, et al (The Oncologist, 2015).

The study

• Authors: A. Hercbergs, R.E. Johnson, O. Ashur-Fabian, D.H. Garfield, P.J. Davis
• Journal: The Oncologist
• Published: 2015;20(1):72-6
• Cited by: 68 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: 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 And Methods: 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.

Results: 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.

Conclusion: 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.

©AlphaMed Press.

In plain English

This article was not about asbestos. It reported thyroid-hormone treatment in 23 people with advanced, incurable solid tumors, one of whom had pleural mesothelioma. It was a retrospective analysis of patients advised by one author on a compassionate-need basis. Treatment lowered blood levels of the hormone thyroxine (T4) while giving another thyroid hormone, triiodothyronine (T3), to prevent an underactive thyroid. Patients had also received conventional chemotherapy or radiation, or both. Survival was compared with expected figures from cancer databases and published reports, not with a control group. Of the 23 patients, 19 (83%) survived more than 12 months and 12 (52%) more than 24 months, against an estimated 1 of 23 expected to survive 24 months. The authors reported that actual survival differed significantly from expected survival. The mesothelioma patient, a 74-year-old man, was still alive at 19 months when the study was submitted, against an expected median of 10 months. The authors described the study as uncontrolled with frank limitations. They noted small numbers per cancer type and missing functional-status data, and called for prospective controlled trials.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Retrospective, uncontrolled observational analysis of a consultative compassionate-care case series, with survival compared against expected survival from cancer databases and literature
• Who was studied: 23 patients (15 women, 8 men) with stage IV, recurrent or progressive solid tumors deemed incurable. Tumors were of the brain, ovary, lung, pancreas, salivary gland and breast, plus mesothelioma and soft-tissue sarcoma. One patient had pleural mesothelioma. Patients were at sites within and outside the U.S.
• Exposure: No asbestos exposure was studied. The intervention was medically lowering serum free thyroxine (FT4). In 12 patients this used methimazole plus L-T3. In 9 patients with pre-existing hypothyroidism, L-T3 was substituted for L-T4. Two patients were already on L-T3, and conventional treatment was not interrupted.
• Main results:
  • In all 23 patients, 19 (83%) survived more than 12 months and 12 (52%) more than 24 months, versus an estimated 1 of 23 (4.4%) expected to survive 24 months
  • The difference between actual and expected survival was reported as statistically significant (p less than .01) for the whole group (n=23), for men only (n=8) and for women only (n=15)
  • The pleural mesothelioma patient (man, 74) survived 19 months and was alive at submission; expected median survival was 10 months and the odds figure was 15%
  • Tumor response was reported as complete in 5 patients and partial in 18 patients (all 23)
  • Side effects were reported infrequently. No clear methimazole-related toxicity could be differentiated from that of concurrent chemotherapy.
• The authors' conclusion: The authors suggested the results may represent a novel, inexpensive, nontoxic approach for solid tumor patients. They concluded that the approach should be tested in prospective controlled trials.
• Limitations the authors state:
  • Uncontrolled observational experience
  • The observations came from consultations, not from a prospective controlled study
  • Statistical analysis was limited by small numbers of patients in each disease category
  • No estimates of the treated patients' functional status were available
  • Patients who did not achieve FT4 depletion for at least 3 months, or who discontinued treatment, were excluded from the analysis

Topics

Medical terms in this study, explained in our Lexicon: Treating Physician, Mesothelioma, Sarcoma, Epidemiology.

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