Study of Euthyroid Hypothyroxinemia in Metastatic Breast Carcinoma
| Status: | Recruiting |
|---|---|
| Conditions: | Breast Cancer, Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | 18 - 105 |
| Updated: | 3/24/2019 |
| Start Date: | March 1, 2019 |
| End Date: | January 2023 |
| Contact: | Mary Amos, RN, CCRC |
| Email: | mary.amos@aultman.com |
| Phone: | 330-363-4162 |
A Single Arm Phase II Pilot Study of Euthyroid Hypothyroxinemia in Metastatic Breast Carcinoma
Up to one third of breast cancer patients have hypothyroidism or hyperthyroidism. L-thyroxine
(T4), or Synthroid, is the most commonly prescribed agent for the management of
hypothyroidism in the US. However, there are data suggesting that triiodothyronine (T3) may
have benefits in preventing disease progression over l-thyroxine (T4).
(T4), or Synthroid, is the most commonly prescribed agent for the management of
hypothyroidism in the US. However, there are data suggesting that triiodothyronine (T3) may
have benefits in preventing disease progression over l-thyroxine (T4).
It is estimated that there are approximately 155,000 living with metastatic breast cancer in
the US and the number is estimated to increase over the next years (SEER data). Although
their median survival has improved over the last 2 decades from 17 months to approximately 24
months attributed to newer treatments, there is an ongoing need for additional strategies and
research to improve survival and quality of life.
Many studies have explored the connection between hypothyroidism and hyperthyroidism and
breast cancer with varied results ranging up to one third prevalence. Low T3 and elevated TSH
levels have been detected in newly diagnosed breast cancer patients. Other studies have
suggested that some of the common symptoms reported by breast cancer survivors such as
fatigue and depression can be attributed to subclinical hypothyroidism.
L-thyroxine (T4) is the most commonly prescribed agent for the management of hypothyroidism
in the US. However, there are data suggesting that T4 is a potent pro-oncogenic agent.
Proposed mechanisms include stimulation of mitogenesis, angiogenesis and resistance to
apoptosis, opposition of anti-PDL-1 and radiation effects. It has been postulated that the
avbeta3integrin that is universally expressed on cancer cells harbors a thyroid hormone
receptor and T4 interacts with it.
Triiodothyronine (T3) on the other hand, is significantly less oncogenic and less mitogenic
and is downstream of T4 which is a T3 pro-hormone. Therefore, exogenous supplementation of T3
would decrease the T4 levels creating the desired state of euthyroid hypothyroxiemia.
The rationale of this study is to replace L-thyroxine (T4) with Triiodothyronine (T3) in
hypothyroid patients with metastatic breast carcinoma while they continue to receive standard
systemic therapy, titrating the dose to achieve a state of euthyroid hypothyroxinemia which
is turn would result in a lower risk of disease progression and improved survival by lowering
the concentration of T4.
the US and the number is estimated to increase over the next years (SEER data). Although
their median survival has improved over the last 2 decades from 17 months to approximately 24
months attributed to newer treatments, there is an ongoing need for additional strategies and
research to improve survival and quality of life.
Many studies have explored the connection between hypothyroidism and hyperthyroidism and
breast cancer with varied results ranging up to one third prevalence. Low T3 and elevated TSH
levels have been detected in newly diagnosed breast cancer patients. Other studies have
suggested that some of the common symptoms reported by breast cancer survivors such as
fatigue and depression can be attributed to subclinical hypothyroidism.
L-thyroxine (T4) is the most commonly prescribed agent for the management of hypothyroidism
in the US. However, there are data suggesting that T4 is a potent pro-oncogenic agent.
Proposed mechanisms include stimulation of mitogenesis, angiogenesis and resistance to
apoptosis, opposition of anti-PDL-1 and radiation effects. It has been postulated that the
avbeta3integrin that is universally expressed on cancer cells harbors a thyroid hormone
receptor and T4 interacts with it.
Triiodothyronine (T3) on the other hand, is significantly less oncogenic and less mitogenic
and is downstream of T4 which is a T3 pro-hormone. Therefore, exogenous supplementation of T3
would decrease the T4 levels creating the desired state of euthyroid hypothyroxiemia.
The rationale of this study is to replace L-thyroxine (T4) with Triiodothyronine (T3) in
hypothyroid patients with metastatic breast carcinoma while they continue to receive standard
systemic therapy, titrating the dose to achieve a state of euthyroid hypothyroxinemia which
is turn would result in a lower risk of disease progression and improved survival by lowering
the concentration of T4.
Inclusion Criteria:
- Age greater than or equal to 18
- Male or female with diagnosis of metastatic breast carcinoma and documented history of
hypothyroidism .
- TSH level within normal range at baseline
- Life expectancy estimated > 3 months
- Ability and willingness to provide informed consent
Exclusion Criteria:
- Life expectancy estimated to be less than 3 months
- Is currently pregnant or intends to become pregnant during the duration of the study
- Active angina, NYHA advanced [Class III/IV] CHF, or uncontrolled cardiac arrhythmia
within 6 months of enrollment
- History of thyrotoxicosis
- History of adrenal insufficiency
- Hypersensitivity to any active or extraneous constituents in Triiodothyronine
(T3)/liothyronine sodium
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