Hormonal Therapy

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HORMONAL THERAPY

Hormonal therapy is one of the major modalities of medical treatment for cancer. It involves the manipulation of the endocrine system through administration of specific hormones, particularly steroid hormones, or drugs which inhibit the production or activity of such hormones (hormone antagonists). Because steroid hormones are powerful drivers of gene expression in certain cancer cells, changing the levels or activity of certain hormones can cause certain cancers to stop growing, or even undergo cell death. Surgical removal of endocrine organs, such as orchiectomy (removal of testes) and oophorectomy (removal of ovaries) are also a form of hormonal therapy.

Hormonal therapy is used for several types of cancers derived from hormonally responsive tissues, including the breast, prostate, endometrium, and adrenal cortex. Hormonal therapy may also be used in the treatment of paraneoplastic syndromes or to ameliorate certain cancer- and chemotherapy-associated symptoms, such as anorexia.

Different types of Harmonal therapies are:-

1. Drugs which inhibits the harmone synthesis:-

a) Aromatase inhibitors
b) gnRH Analogue

a) Aromatase inhibitors

Aromatase inhibitors are an important class of drugs used for the treatment of breast cancer in postmenopausal women. At menopause, estrogen production in the ovaries ceases, but other tissues continue to produce estrogen through the action of the enzyme aromatase. These drugs block this enzyme 'aromatase' and hence, block destroys production.

Letrozole and anostrazole are two main drugs of this class

b) GnRH analogs:-

This Class of drugs are used to induce a chemical castration, that is, complete suppression of the production of estrogen and progesterone from the female ovaries, or complete suppression of testosterone production from the male testes. This is due to a negative feedback effect of continuous stimulation of the pituitary gland by these hormones. Leuprolide and goserelin are examples of these drugs which are used primarily for the treatment of hormone-responsive prostate cancer.

2. Hormone receptor antagonists

Hormone receptor antagonists bind to the normal receptor for a given hormone and prevent its activation. These include 2 main clan of drugs:-

a) Selective estrogen receptor modulators (SERMS)

Selective estrogen receptor modulators (SERM's) are an important class of hormonal therapy agents which act as antagonists of the estrogen receptor and are used primarily for the treatment and chemoprevention of breast cancer e.g. temoxifes

b) Antiandrogens

Antiandrogens are a class of drug which bind and inhibit the androgen receptor, blocking the growth- and survival-promoting effects of testosterone on certain prostate cancers. Flutamide and bicalutamide are antiandrogens which are frequently used in the treatment of prostate cancer, either as long-term monotherapy, or in the initial few weeks of GnRH analog therapy.

3. Hormone supplementation

While most hormonal therapy strategies seek to block hormone signalling to cancer cells, there are some instances in which supplementation with specific hormone agonists may have a growth-inhibiting, or even cytotoxic effect on tumor cells.

a) Progestagens

Progestins (progesterone-like drugs) such as megestrol and medroxyprogesterone have been used for the treatment of hormone-responsive, advanced breast cancer, endometrial cancer, and prostate cancer.

b) Androgens

The androgen (testosterone-like drug) Fluoxymesterone is occasionally used for the treatment of advanced breast cancer.

c) Estrogens

The estrogen agonist Diethylstilbestrol (DES) is occasionally used to treat prostate cancer through suppression of testosterone production.

d) Somatostatin analogs(Octreotide)

It is used for suppression of the hormonal syndromes which accompany several pancreatic islet cell tumors, including the Zollinger-Ellison syndrome of gastrinoma and the chronic hypoglycemia of insulinoma. It is also effective in suppression of the carcinoid syndrome, caused by advanced or extra-gastrointestinal carcinoid tumors. Octreotide may also be used for treatment of severe diarrhea caused by 5-fluorouracil chemotherapy or radiation therapy.

4. Non-medical hormonal interventions

Surgical castration, or removal of the testes in males and ovaries in females, have been widely used in the past to treat hormone-responsive prostate cancer and breast cancer respectively. In women at high risk for breast cancer and ovarian cancer due to mutations in the BRCA1 or BRCA2 genes, bilateral salpingo-oophorectomy (removal of the fallopian tubes and ovaries) not only prevents ovarian cancer, but reduces their future risk for breast cancer by reducing lifetime estrogen exposure.