Generic Name: Estramustine Phosphate Sodium
Class: Antineoplastic Agents
VA Class: AN900
Chemical Name: 3-[bis(2-chloroethyl)carbamate] 17-(dihydrogen phosphate)-estra-1,3,5(10)-triene-3,17-diol (17β) disodium salt
Molecular Formula: C23H30Cl2NNa2O6P
CAS Number: 2998-57-4
Uses for Emcyt
Combination therapy with etoposide, paclitaxel, or vinblastine9 may result in higher objective response rates and greater improvements in subjective parameters (e.g., pain) for treatment of hormone-refractory disease.2 9
Emcyt Dosage and Administration
Consult specialized references for procedures for proper handling and disposal of antineoplastics.
Food or calcium-containing products may decrease absorption.1 2 13 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).1 2 13
Available as estramustine phosphate sodium; dosage expressed in terms of estramustine phosphate.1
Cautions for Emcyt
Active thrombophlebitis or thromboembolic disorders, except when such conditions are caused by the tumor mass, and clinician judges that anticipated benefits outweigh potential risks.1
Risk of adverse effects from estrogenic metabolites; consider cautions, precautions, and contraindications associated with estrogens.15
Risk of thrombotic and thromboembolic disorders,13 including thrombophlebitis,1 3 AMI,1 11 pulmonary embolism,1 10 13 cerebrovascular accident,1 11 and leg cramps.1 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.1
Endocrine and Metabolic Effects
Risk of angioedema, rash, and pruritus.1
Risk of exacerbation of preexisting or incipient peripheral edema1 3 4 8 9 or CHF.1 3 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.1 13
Fetal/Neonatal Morbidity and Mortality
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.1 Risk of hypocalcemia in patients with prostate cancer and osteoblastic metastases; closely monitor calcium concentrations.a
Not intended for use in women.15
Safety and efficacy not established; use not recommended in pediatric patients.15
Decreased metabolism in patients with hepatic impairment; use with caution.1
May influence metabolism of calcium and phosphorus; use with caution.1
Common Adverse Effects
Nausea, diarrhea, minor GI upset, breast tenderness, breast enlargement, edema, elevated AST [SGOT] and/or LDH concentrations, dyspnea.1
Interactions for Emcyt
Calcium-containing Foods or Drugs
Potential decreased absorption when administered concomitantly with calcium-containing foods or beverages (e.g., milk, milk products) or drugs (e.g., calcium-containing antacids).1 3 13 (See Oral Administration under Dosage and Administration.)
After oral administration, approximately 75% of estramustine phosphate absorbed into GI tract tissues and rapidly dephosphorylated to cytotoxic estramustine, most of which is subsequently oxidized to an active cytotoxic metabolite, estromustine.1 2 3 9 13 Relative bioavailability of estromustine is approximately 44%.2
Calcium-containing foods or beverages (e.g., milk, milk products) may decrease absorption.1
Estramustine and estromustine are distributed into prostatic carcinoma tissues and plasma; the tumor to plasma concentration ratio of estramustine or estromustine is approximately 6 or 1, respectively.3
Approximately 10–20% of estramustine or estromustine is metabolized to estradiol or estrone, respectively.2 3 9 13 Markedly elevated estradiol concentrations detected as early as 1 week of estramustine phosphate initiation; may persist for 7–12 weeks after discontinuance.15
After oral administration, mean elimination half-life of estromustine was approximately 10.3 hours.3
Decreased metabolism in patients with hepatic impairment.1
Advice to Patients
Importance of using effective contraception method during therapy; if pregnancy occurs in the partner of a patient, advise patient and partner of risk to the fetus.1
Importance of informing clinicians of existing or contemplated therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.1
Importance of informing patients of other important precautionary information. (See Cautions.)
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
140 mg (of estramustine phosphate)
AHFS DI Essentials. © Copyright, 2016, American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814. Review Date: September 06, 2016.
1. Pharmacia. Emcyt (estramustine phosphate sodium) capsules prescribing information. Kalamazoo, MI; 1999 Feb.
2. Perry CM, McTavish D. Estramustine phosphate sodium: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in prostate cancer. Drugs Aging. 1995; 7:49-74. [PubMed 7579781]
3. Bergenheim AT and Henriksson R. Pharmacokinetics and pharmacodynamics of estramustine phosphate. Clin Pharmacokinet. 1998; 34:163-72. [PubMed 9515186]
4. Anon. Drug of choice for cancer chemotherapy. Med Lett Drugs Ther. 2000; 42:83-92. [PubMed 10994034]
5. Prostate cancer. From: PDQ Information for Health Care Professionals (database). Bethesda, MD: National Cancer Institute; 2002 Feb. From NCI website.
6. Benson RC, Wear JB, and Gill GM. Treatment of stage D hormone- resistant carcinoma of the prostate with estramustine phosphate. J Urol. 1979; 121:452-4. [IDIS 122742] [PubMed 439216]
7. Mittelman A, Shukla SK, and Murphy GP. Extended therapy of stage D carcinoma of the prostate with oral estramustine phosphate. J Urol. 1976; 115:409-12. [PubMed 1263317]
8. de Kernion JN, Murphy GP, Priore R et al. Comparison of flutamide and Emcyt in hormone- refractory metastatic prostatic cancer. Urology. 1988; 31:312-7. [PubMed 3281365]
9. Hudes G, Einhorn L, Ross E et al. Vinblastine versus vinblastine plus oral estramustine phosphate for patients with hormone-refractory prostate cancer: a Hoosier Oncology Group and Fox Chase Network phase III trial. J Clin Oncol. 1999; 17:3160-6. [IDIS 436791] [PubMed 10506613]
10. Kuhn MW, Weissbach L, and Hinke A for the Prostate Cancer Study Group. Primary therapy of metastatic prostate carcinoma with depot gonadotropin-releasing hormone analogue goserelin versus estramustine phosphate. Urology. 1994; 43(Suppl 2):61-7. [PubMed 8116135]
11. Johansson JE, Andersson SO, Beckman KW et al. Clinical evaluation of flutamide and estramustine as initial treatment of metastatic carcinoma of prostate. Urology. 1987; 29:55-9. [PubMed 3798631]
12. Roessler W, Hinke A, and Wieland WF. Experience in advanced prostatic cancer: orchiectomy and flutamide versus orchiectomy and estramustine phosphate. Urology. 1994; 43(Suppl 2):57-60. [PubMed 8116134]
13. Rowinsky EK and Tolcher AW. Antimicrotubule agents. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds. Cancer: principles and practice of oncology. 6th ed. Philadelphia: Lippincott Williams & Wilkins; 2001:431- 52.
14. Carroll PR, Lee KL, Fuks ZY et al. Cancer of the prostate. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds. Cancer: principles and practice of oncology. 6th ed. Philadelphia: Lippincott Williams & Wilkins; 2001:1418-79
15. Pharmacia, Kalamazoo, MI: Personal communication.
a. Pharmacia. Emcyt (estramustine phosphate sodium) capsules prescribing information. Kalamazoo, MI; 2003 Mar.
b. Hudes G, Haas N, Yeslow G et al. Phase I clinical and pharmacologic trial of intravenous estramustine phosphate. J Clin Oncol. 2002; 20:1115-27. [IDIS 479067] [PubMed 11844837]