Class: Alkylating-like agent (Nitrogen mustard derivative conjugated to estradiol phosphate).
- Unique Feature: Combination of a nitrogen mustard moiety with an estrogen component.
Mechanism of Action
- Unlike classic alkylators, estramustine does not primarily cross-link DNA.
- Instead, it binds to microtubule-associated proteins and tubulin, disrupting spindle formation → inhibition of mitosis.
- Estrogenic component also contributes (accumulates in prostate tissue).
Clinical Uses
- Hormone-refractory (castration-resistant) prostate cancer.
- Rarely used today due to limited efficacy and toxicity compared with newer androgen receptor inhibitors (enzalutamide, apalutamide) and taxanes (docetaxel, cabazitaxel).
Dosing
- Oral: 280 mg PO 3–4 times daily (approx. 10–16 mg/kg/day in divided doses).
- Taken on an empty stomach to improve absorption.
Toxicities
- Estrogen-related: gynecomastia, fluid retention, thromboembolic events (DVT, PE, stroke), cardiovascular risk (MI, HF).
- GI: nausea, vomiting.
- Hepatotoxicity (elevated LFTs, rare cholestasis).
- Myelosuppression is not a major feature, unlike classic nitrogen mustards.
Monitoring
- Blood pressure, cardiovascular status.
- LFTs.
- Signs of thromboembolism.
- Weight and fluid status (due to estrogenic effects).
In summary:
Estramustine is an oral nitrogen mustard–estradiol conjugate used mainly in castration-resistant prostate cancer. Unlike other mustards, it works by disrupting microtubule function rather than DNA cross-linking. Toxicities are mostly estrogen-related (thromboembolism, gynecomastia, fluid retention), which has limited its modern use.