Estramustine

Estramustine is an antineoplastic agent belonging to the pharmacological class of microtubule-damaging agents.

Estramustine is FDA-approved for the treatment of advanced prostatic carcinoma.

The gastrointestinal tract only absorbs about 75%, which is then lessened by food and builds up in the plasma and tissues of prostatic cancer. Estradiol, estrone, and Estramustine are produced during liver metabolism. The principal elimination method is ethanol (<1% excreted in urine).

The most common side effects of Estramustine include nausea, vomiting, increased liver enzymes, anaemia (low number of red blood cells), and fluid retention.

Estramustine is available in capsules.

The molecule is available in India, the United States, Canada, countries within the European Union, Australia, Japan and South Korea.

Estramustine is an antineoplastic agent belonging to the pharmacological class of microtubule-damaging agents.

Estramustine disrupts microtubule growth's regular process. In contrast to medications such as colchicine, which depolymerizes microtubules in vivo, Estramustine hyper-stabilizes their structure, thereby stopping their function. This eliminates the cell's capacity to make flexible use of its cytoskeleton. Estramustine specifically binds to tubulin's β-subunit. Microtubules' "building block" is tubulin, and Estramustine binding secures these building blocks. The ensuing microtubule/Estramustine complex is incapable of breaking down. Because microtubules' role as the cell's transportation network depends on their ability to shorten and lengthen (a process known as dynamic instability), this harms cell function. During mitosis, for instance, chromosomes depend on this microtubule characteristic. Additional studies have shown that Estramustine causes the cancer cells to undergo either programmed cell death, or apoptosis, by attaching to and inhibiting the activity of the protein Bcl-2 (B-cell leukaemia 2), which prevents apoptosis.

Estramustine is available in the form of oral capsules.

Capsules: To be swallowed whole with water/liquid. Do not chew, crush or break it.

As the physician recommends, take the medication orally 3-4 times daily; it can be taken with or without food as directed.

Prostate cancer: By preventing the growth and multiplication of cancer cells, Estramustine helps manage prostate cancer. It reduces tumour size, lessens symptoms, and controls the course of the illness. For those with prostate cancer, its combination therapy offers hope and better outcomes by frequently relieving symptoms, reducing the likelihood of cancer spreading, and possibly extending survival. Prostate cancer symptoms include trouble urinating, though the illness can also occasionally manifest as a symptomless state.

Patients with progressive or metastatic prostate cancer should be indicated with estramustine as palliative care.

Orally: Take Estramustine capsules orally with water, usually three or four times daily. The prescription advises ingestion on an empty stomach, an hour before or two hours after meals. Swallow the capsules whole, avoiding chewing or opening them. Consistency in dosing times proves critical. Adhere to regular intake for maximum benefit. Ensure standard daily intake times as directed, basing the dosage on your medical condition, weight, and response to therapy.

The dosage and duration of treatment should be as per the treating physician's clinical judgment.

Estramustine is available as capsules.

Prostate Carcinoma

palliative care for prostate cancer that has spread or is getting worse

14 mg/kg divided every 6 to 8 hours PO

Treat for 30 to 90 days to assess the benefits of continuing therapy; maintain with treatment as long as a positive response persists.

When taking Estramustine, follow dietary guidelines for improved safety. Incorporate vegetables like cauliflower, cabbage, broccoli, spinach, and kale, which inhibit prostate cancer growth and reduce its risk. Limit dairy product intake to lower the likelihood of prostate cancer. Reduce red meat consumption, as a high intake of cooked meat may elevate prostate cancer risk.

The dietary restriction should be individualized as per patient requirements.

The adverse reactions related to Estramustine can be categorized as:

Common Adverse Effects: Edema, dyspnea, nausea, diarrhoea, breast tenderness

Less Common Adverse Effects: Lethargy, insomnia, cerebrovascular accidents, myocardial infarctions, thrombophlebitis, pulmonary embolism, congestive heart failure, easy bruising, anorexia, vomiting, pruritus, dry skin, impotence, leg cramps, leukopenia, decreased testosterone, and abnormality in hepatic enzymes and/or bilirubin levels.

Rare Adverse Effects: Embolism, MI, CHF, angioedema.

The clinically relevant drug interactions of Estramustine are briefly summarized here.

Drug interactions: Estramustine may interact with antacids (magnesium hydroxide, aluminium hydroxide), vitamins, herbal supplements, antifungal medications (ketoconazole, itraconazole), and many others.

Drug-food interactions: Milk, milk products, and calcium-rich foods may impair the absorption of Estramustine,

Drug-disease interactions: Patients who suffer from severe kidney and liver failure, pituitary or adrenal gland issues, heart failure, irregular heartbeat, elevated blood pressure, or hypoglycemia should use Estramustine with caution.

The common side effects of Estramustine include:

Nausea

Vomiting

Dizziness

Heartburn

Headache

Anaemia (low number of red blood cells)

Increased liver enzymes

Decreased white blood cell count

Loss of Appetite

GI bleeding

Thirst

Edema

Diarrhea

Breast enlargement in male

Pregnancy Category X (FDA): Avoid using while pregnant. The risks are more significant than the potential benefits. There are safer options available.

It is not recommended to use Estramustine while pregnant. It might be harmful to the fetus and have teratogenic effects. Studies on its use in pregnant women are insufficient. Notify your doctor right away if you become pregnant while receiving Estramustine or if you decide to become pregnant while receiving treatment. Inform patients of any possible hazards to the developing fetus. Pregnancy should be avoided for a certain amount of time, both during and after therapy.

It is advised to use contraception both during and for a while after treatment ends. The patient should be informed of the possible risks to the fetus and should stop taking Estramustine immediately if pregnancy develops while on the medication.

Information regarding the use of Estramustine while nursing is inadequate. Nursing should be avoided while taking this medication due to possible adverse effects on the infant. It is advisable to temporarily halt treatment or seek advice from a healthcare professional for alternative feeding options to mitigate any potential harm to the nursing infant.

As per the FDA, Estramustine in Pediatric patients has not been recommended.

Estramustine safety and efficacy in the geriatric population have not been extensively studied. Caution is advised due to potential heightened sensitivity to medication in elderly individuals, necessitating close monitoring for adverse effects and adjusting doses based on individual health conditions.

Prostate Carcinoma

Palliative care for prostate cancer that has spread or is progressing

14 mg/kg PO given every 6–8 hours

To determine the benefits of ongoing therapy, treat for 30 to 90 days; continue treatment for as long as a positive response persists.

Renal impairment: No dosage adjustment is required.

Mild to moderate: Dosage adjustment may be needed.

Severe: Contraindicated.

The physician should be vigilant about the knowledge pertaining to the identification and treatment of overdosage of Estramustine.

Overconsumption of Estramustine may lead to nausea, vomiting, and diarrhoea, along with hematologic abnormalities such as leukopenia or abnormal liver function tests.

There is no specific antidote or treatment for overdosage of Estramustine. If an overdose occurs, promptly empty the stomach through gastric lavage and initiate symptomatic treatment. Continuously monitor hematologic and hepatic functions for at least six weeks post-overdose of Estramustine Capsules. Vigilant observation and appropriate management are crucial to address potential complications arising from excessive ingestion. Immediate medical attention is necessary in such cases.

Timely medical intervention plays a crucial role in managing Estramustine overdose, ensuring careful monitoring and proper care to address symptoms and prevent complications.

Estradiol, a type of estrogen, and a nitrogen mustard molecule combine to create the unique compound known as Estramustine. As soon as the nitrogen mustard component enters the body, it activates and starts the alkylation process. During this process, the compound is directly bound to the DNA or other critical cellular constituents. This interaction damages DNA, especially in cancer cells that divide quickly and ultimately cause cell death. The purpose is to decrease the size of the tumour by eliminating these malignant cells.