Integrative Cancer Therapy
Hormones. Estrogens and peptide hormones play important roles in the development and progression of lung cancer, whereas melatonin and thyroid hormones are pivotal in the stabilization and inhibition of lung cancer in men (Zhou XD et al 2002; Bhatavdekar JM et al 1994).
Estrogens: Whether produced in the body or obtained through hormone replacement therapy, estrogens may be involved in lung cancer development and progression (Inoue M et al 2006; Liu Y et al 2005). Lung cancer tissue contains an abundance of estrogen receptors, which are not found in normal lung tissue, thus opening up a possibility of antiestrogen therapy for patients with advanced lung cancer displaying estrogen receptors in their tumors (Canver CC et al 1994).
If a patient’s lung cancer displays estrogen receptors, then reducing estrogen levels in the body (because estrogen stimulates cancer growth), in addition to standard treatments, is potentially beneficial. Because body fat is a source of estrogen, it is important to establish and maintain a healthy weight (Siiteri PK 1987). In addition, the following nutritional supplements with natural antiestrogen properties show promise:
- Melatonin has multiple antiestrogen actions and decreases estradiol levels in the body (Sanchez-Barcelo EJ et al 2005; Rato AG et al 1999).
- Vitamin K2 (menaquinone), known for its blood coagulation effects, decreases the ratio of estradiol to estrone, slowing down estrogen activity (Otsuka M et al 2005).
Furthermore, estrogen levels in the body can be lowered by counteracting obesity (see the Obesity chapter) and keeping a low-fat diet (Deslypere JP 1995; Alavanja MC et al 1994; Kolonel LN 1993).
Peptide hormones: Peptide hormones act as growth factors and increase lung cancer growth (Moody TW 2006). For example, SCLC and NSCLC both produce gastrin-releasing peptide (GRP), neurotensin and adrenomedullin, which are growth factors, and as the name suggests, they increase lung cancer growth (Moody TW 2006). However, growth factor antagonists prevent SCLC growth in vitro and have been studied in Phase III clinical trials (Moody TW et al 2001). These growth factor antagonists may provide new treatments for SCLC patients in the future.
Melatonin: The most widely investigated anticancer hormone is melatonin (Lissoni P et al 2001). It has been used both alone and in combination with most standard cancer treatments because it improves both survival and quality of life (Lynch E 2005). Advanced lung cancer patients show a progressive reduction in melatonin levels (Mazzoccoli G et al 1999), and their daily sleep-wake patterns are disrupted (Levin RD et al 2005; Lissoni P et al 1998). However, even in patients for whom no other standard treatment is offered, melatonin with aloe vera extract stabilizes the cancer growth and improves survival (Lissoni P et al 1998).
In a study of 100 lung cancer patients who were randomized to receive either chemotherapy alone or chemotherapy with melatonin (20 mg/day orally), the five-year survival rates were significantly higher for the group of patients who received melatonin. In addition, no patient treated with chemotherapy alone was alive after two years, whereas five-year survival was achieved in three of 49 patients (6 percent) treated with chemotherapy and melatonin. Furthermore, lung cancer patients treated with melatonin tolerate chemotherapy better and have less-serious side effects (Lissoni P et al 1999, 2003a,b).
Thyroid hormones: Thyroid stimulating hormone (TSH) controls 25 percent of the body’s metabolism, thereby affecting how quickly cells (including cancer cells) grow and die. Therefore, making the thyroid underactive (a condition known as hypothyroidism) by reducing TSH levels in the body may slow down cancer growth. Hypothyroidism can be achieved artificially with the prescription drugs propylthiouracil (PTU) or Tapazole®.
When All Else Fails: Increase Survival with Hypothyroidism
A case in point: A patient originally diagnosed with metastatic lung cancer (i.e., lung cancer that had spread throughout the body) was admitted to the hospital because of a rare complication of underactive thyroid disease (i.e., hypothyroidism) called myxedema coma. This rare clinical condition can be caused by insufficient thyroid hormone (T4) replacement, infection, cold exposure, trauma, or the drug amiodarone (which causes thyroid hormone abnormalities) (Hondeghem LM 1987). The myxedema coma occurred just two months after the patient was diagnosed with metastatic lung cancer. On examination for myxedema coma, the patient was found to have no evidence of remaining cancer, and five years later the lung cancer had still not returned (i.e., he remained in remission). It was concluded that spontaneous remission (complete permanent disappearance) of the lung cancer had occurred due to a severe deficiency of thyroid hormone; in other words, thyroid hormone deprivation had induced total tumor cell death (Hercbergs A 1993, 1999).
If a lung cancer patient also has hypothyroidism or subclinical hypothyroidism, it may be wise to avoid taking too much thyroid hormone to correct this condition. By contrast, if a lung cancer patient has an overactive thyroid (hyperthyroidism), it is essential to reduce the levels of the thyroid hormones triiodothyronine (T3) and T4 to normal (or lower) as quickly as possible (typically with PTU or Tapazole®) because hypothyroidism or inadequate thyroid hormone replacement prolongs survival of lung cancer patients and in some cases causes spontaneous remission of the lung cancer (Garfield D 2002). TSH, T3, and T4 can be measured by a simple blood test.