Estramustine Phosphate Sodium

Abstract

Estramustine phosphate is approved by the Food and Drug Administration for oral use in the palliative treatment of patients with metastatic and/or progressive carcinoma of the prostate. Estramustine is a conjugate of 17 beta-estradiol and the carbamate of nitrogen mustard. Although its therapeutic efficacy has been demonstrated, it is not clear to what extent each constituent contributes to estramustine's effectiveness. Estramustine phosphate therapy achieves objective response rates of 60-90 percent in advanced stage D prostatic cancer patients with no prior hormonal therapy. These results are consistent with those obtained with conventional hormonal therapy in similar patient populations. Therapeutic efficacy does not appear to increase when estramustine is used concurrently with other cytotoxic chemotherapeutic agents. An objective response rate of 20-30 percent can be anticipated in patients refractory to conventional hormonal therapy. It is in this group, the estrogen-resistant patients, that estramustine shows the most promise. Adverse effects of estramustine are similar to those of diethylstilbestrol. Gastrointestinal and cardiovascular side effects appear to be the most important and may be severe enough to require discontinuation of therapy.

Synthesis and Antiproliferative Activity of Some Androstene Oximes and Their O‐Alkylated Derivatives

“…Inhibition of specific enzymes like aromatase and 5α‐reductase are the frontline treatment approaches for breast and prostate carcinoma . Extensive chemical modifications of the steroid skeleton have been carried out to synthesize many potent antineoplastic agents, which could target hormone‐dependent cancers like prostate (e.g., finasteride, dutasteride), breast (e.g., exemestane), and uterine carcinomas .…”

“…To obtain compounds with higher degree of oxidation in ring A, diacetoxy 6-oxime 6 was hydrolyzed using methanolic KOH to yield 3b,17b-dihydroxy-6E-hydroximino-androst-4-ene (7), which was further oxidized with CrO 3 /pyridine complex to obtain 3,17-dioxo-6E-hydroximino-androst-4-ene (8) [16].…”

Steroid Conjugates as Potential Anti-Cancer Agents

“…Так, исследования противоопухолевого препарата эстрамустина фосфата 7 показали, что этот конъюгат лишен ДНК-алкилирующей активности, а его противоопухолевый эффект обусловлен взаимодействием с тубулином, вызывающим деполимеризацию микротрубочек, а также влиянием на цитоскелет, клеточный цикл, гомеостаз железа, апоптоз и клеточный сигналинг [37][38][39][40].…”

Chemotherapy for Prostate Cancer

“…The results of initial breast cancer trials were disappointing with no apparent correlation between estrogen receptor status and responses; however, it proved to have activity in prostate cancer. 15,16 In addition to its estrogenic activity that can cause castrate levels of testosterone, 17 estramustine exerts cytotoxic effects by interfering with the microtubule structure and binding to the nuclear matrix. 18 Estramustine has been approved by the FDA for use in patients with metastatic prostate cancer.…”