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Uses

Prostate Cancer

Palliative treatment of metastatic and/or progressive prostate cancer.

Considered by many clinicians to be an alternative to conventional measures (e.g., orchiectomy, hormonal therapy); generally used in treatment of hormone-refractory prostate cancer.

Combination therapy with etoposide, paclitaxel, or vinblastine may result in higher objective response rates and greater improvements in subjective parameters (e.g., pain) for treatment of hormone-refractory disease.

Dosage and Administration

General

• Consult specialized references for procedures for proper handling and disposal of antineoplastics.

Administration

Oral Administration

Administer orally 3 or 4 times daily.

Food or calcium-containing products may decrease absorption. Administer orally 1 hour before or 2 hours after meals with water; avoid concomitant administration with calcium-containing foods or beverages (e.g., milk, milk products) or drugs (e.g., calcium-containing antacids).

Dosage

Available as estramustine phosphate sodium; dosage expressed in terms of estramustine phosphate.

Adults

Prostate Cancer

Oral

14 mg/kg (i.e., one 140-mg capsule for each 10 kg or 22 lb of body weight) daily in 3 or 4 divided doses. In clinical studies in the US, most patients received dosages of 10–16 mg/kg daily.

Administer 30–90 days before assessing potential benefits of continuing. Continue therapy as long as response is satisfactory; some patients have received >3 years.

Cautions

Contraindications

• Known hypersensitivity to estramustine, estradiol (or other estrogens), nitrogen mustard, or any ingredient in the formulation.
• Active thrombophlebitis or thromboembolic disorders, except when such conditions are caused by the tumor mass, and clinician judges that anticipated benefits outweigh potential risks.

Warnings/Precautions

Warnings

Estrogenic Effects

Risk of adverse effects from estrogenic metabolites; consider cautions, precautions, and contraindications associated with estrogens.

Risk of breast tenderness and mild or moderate breast enlargement. Gynecomastia and impotence are known estrogenic effects.

Cardiovascular Effects

Risk of thrombotic and thromboembolic disorders, including thrombophlebitis, AMI, pulmonary embolism, cerebrovascular accident, and leg cramps. Use with caution in patients with history of thrombophlebitis, thrombosis, or thromboembolic disorders (especially if associated with estrogen use); caution in patients with cerebrovascular or coronary artery disease.

Hypertension may occur; monitor BP periodically.

Endocrine and Metabolic Effects

Risk of decreased glucose tolerance; patients with diabetes mellitus should be carefully monitored.

Sensitivity Reactions

Risk of angioedema, rash, and pruritus.

Major Toxicities

Cardiovascular Effects

Risk of exacerbation of preexisting or incipient peripheral edema or CHF. Use with caution in patients with conditions that might be aggravated by fluid retention (e.g., CHF, epilepsy, migraine, renal dysfunction), and carefully monitor such patients.

Hepatic Effects

Risk of elevated AST (SGOT), LDH, and/or bilirubin concentrations. Monitor liver function during and for 2 months following discontinuance.

GI Effects

Risk of nausea, diarrhea, and minor GI upset.

General Precautions

Fetal/Neonatal Morbidity and Mortality

Estramustine was not mutagenic in the Ames test; however, estradiol and nitrogen mustard are known mutagens. Avoid pregnancy during therapy.

Metabolic Effects

Potential influence on metabolism of calcium and phosphorus; use with caution in patients with metabolic bone diseases associated with hypercalcemia or in patients with renal impairment. Risk of hypocalcemia in patients with prostate cancer and osteoblastic metastases; closely monitor calcium concentrations.

Specific Populations

Pregnancy

Category X. (See Fetal/Neonatal Morbidity and Mortality under Cautions.) Not intended for use in women.

Lactation

Not intended for use in women.

Pediatric Use

Safety and efficacy not established; use not recommended in pediatric patients.

Geriatric Use

Safety and efficacy not specifically studied to date. Careful monitoring for toxicity recommended.

Hepatic Impairment

Decreased metabolism in patients with hepatic impairment; use with caution.

Renal Impairment

May influence metabolism of calcium and phosphorus; use with caution.

Common Adverse Effects

Nausea, diarrhea, minor GI upset, breast tenderness, breast enlargement, edema, elevated AST [SGOT] and/or LDH concentrations, dyspnea.