The side effects of<unk>  overall have been described as relatively severe. The most common side effects of<unk>  have been reported to be gastrointestinal side effects like nausea, vomiting, and diarrhea, with nausea and vomiting occurring in 40% of men. They are usually mild or moderate in severity, and the nausea and vomiting can be managed with prophylactic antiemetic medications. Nonetheless, severe cases of gastrointestinal side effects with<unk>  may require dose reduction or discontinuation of therapy. Although nausea and vomiting have been reported to be the most common side effects of<unk> , gynecomastia (male breast development) has been found to occur in as many as 83% of men treated with<unk> , and the incidence of erectile dysfunction is possibly similar to or slightly less than the risk of gynecomastia. As a rule, feminization, a gynoid fat distribution, demasculinization, and impotence are said to occur in virtually or nearly 100% of men treated with high-dose estrogen therapy. Decreased sexual activity has also been reported in men treated with<unk> . These side effects are due to high estrogen levels and low testosterone levels. Prophylactic irradiation of the breasts can be used to decrease the incidence and severity of gynecomastia with estrogens. Severe adverse effects of<unk>  are thromboembolic and cardiovascular complications including pulmonary embolism, deep vein thrombosis, stroke, thrombophlebitis, coronary artery disease (ischemic heart disease; e.g., myocardial infarction), thrombophlebitis, and congestive heart failure with fluid retention.<unk>  produces cardiovascular toxicity similarly to diethylstilbestrol, but to a lesser extent in comparison at low doses (e.g., 280 mg/day oral<unk>  vs. 1 mg/day oral diethylstilbestrol). The prostate cancer disease state also increases the risk of thromboembolism, and combination with docetaxel may exacerbate the risk of thromboembolism as well. Meta-analyses of clinical trials have found that the overall risk of thromboembolism with<unk>  is 4 to 7%, relative to 0.4% for chemotherapy regimens without<unk> . Thromboembolism is the major toxicity-related cause of discontinuation of<unk> . Anticoagulant therapy with medications such as aspirin, warfarin, unfractionated and low-molecular-weight heparin, and vitamin K antagonists can be useful for decreasing the risk of thromboembolism with<unk>  and other estrogens like diethylstilbestrol and ethinylestradiol. Adverse liver function tests are commonly seen with<unk> , but severe liver dysfunction is rare with the medication. Central nervous system side effects are rarely seen with<unk> , although enlarged ventricles and neuronal pigmentation have been reported in monkeys treated with very high doses of<unk>  (20–140 mg/kg/day) for 3 to 6 months.<unk>  does not appear to have cytostatic effects in normal brain tissue. In women treated with<unk>  in clinical studies, a few instances of minor gynecological hemorrhages have been observed.<unk>  is described as relatively well tolerated among cytostatic antineoplastic and nitrogen-mustard agents, rarely or not at all being associated with significant hematologic toxicity such as myelosuppression (bone marrow suppression), gastrointestinal toxicity, or other more marked toxicity associated with such agents. In contrast to most other cytostatic agents, which often cause myelosuppression, leukopenia (decreased white blood cell count), and neutropenia (decreased neutrophil count),<unk>  actually produces leukocytosis (increased white blood cell count) as a side effect. In a small low-dose study using 280 mg/day oral<unk>  for 150 days, tolerability was significantly improved, with gastrointestinal irritation occurring in only 15% of men, and there was no incidence of severe cardiovascular toxicity or deep vein thrombosis. In addition, no other side effects besides slight transient elevated liver enzymes were observed. These findings suggest that lower doses of oral<unk>  may be a safer option than higher doses for the treatment of prostate cancer. However, a subsequent 2004 meta-analysis of 23 studies of thromboembolic events with<unk>  found substantial incidence of thromboembolic events regardless of dosage and no association of<unk>  dose with risk of these complications.
Estramustine phosphate
Normustine
GemOx
Bendamustine
Paclitaxel
Lomustine
Ifosfamide
Trifluridine