美国FDA于8月31日批准Xtandi（enzalutamide）治疗已扩散或复发的，甚至已以药物或手术治疗，以减少睾酮的男性晚期（转移性）趋势抵抗前列腺癌。
FDA通过优先审查程序对Xtandi进行了审查，批准它用于先前以另一种抗肿瘤药多西他赛（docetaxel）治疗过的前列腺癌患者。这比目标日期提前了三个月。
“晚期前列腺癌的治疗需要有更多的选择，这对患者而言是重要的，” FDA药品评价和研究中心的血液学和肿瘤学产品办公室主任Richard Pazdur博士指出。“Xtandi是证明能够治疗这种疾病，延长患者生命的最新武器。”
前列腺癌在膀胱下和直肠前方的男性生殖系统腺体形成。男性睾丸激素刺激前列腺肿瘤生长。据美国国家癌症研究所数据估计，2012年有241740人被诊断患有前列腺癌，28170人将死于这种疾病。
在一项有1199名先前接受过多西他赛治疗的转移性趋势抵抗前列腺癌患者参与的研究中，对Xtandi的安全性和疗效作了评估。这项研究的目的是要衡量接受Xtandi者相比安慰剂（糖丸）组总体生存期（至死亡前的时间长度）。接受Xtandi患者的中位总生存期为18.4个月，安慰剂组为13.6个月。
研究中接受Xtandi者报告的最常见副作用有虚弱或疲劳、腰痛、腹泻、关节痛、潮热、组织肿胀 肌肉骨骼疼痛、头痛、上呼吸道感染、头晕、脊髓压迫和马尾神经综合征、肌无力、睡眠困难、下呼吸道感染、尿中带血、刺痛感、焦虑、高血压。
接受Xtandi者中约有1％出现癫痫发作。这些患者中途退出研究。该项临床研究排除了有癫痫发作、脑损伤且意识丧失、过去12个月内暂时脑缺血、中风、脑转移瘤、脑动脉和静脉异常连接病史患者，或服用可能会降低癫痫发作阈值药物的患者。Xtandi对这些患者的安全性尚未知晓。
Xtandi将由Astellas 制药和Medivation两家美国公司共同销售。

Generic Name: capsule
Indications and Usage for Xtandi
Xtandi is indicated for the treatment of patients with metastatic castration-resistant prostate cancer who have previously received docetaxel.
Xtandi Dosage and Administration
Dosing Information
The recommended dose of Xtandi is 160 mg (four 40 mg capsules) administered orally once daily. Xtandi can be taken with or without food [see Clinical Pharmacology (12.3)]. Swallow capsules whole. Do not chew, dissolve, or open the capsules.
Dose Modifications
If a patient experiences a ≥ Grade 3 toxicity or an intolerable side effect, withhold dosing for one week or until symptoms improve to ≤ Grade 2, then resume at the same or a reduced dose (120 mg or 80 mg), if warranted.
Concomitant Strong CYP2C8 Inhibitors
The concomitant use of strong CYP2C8 inhibitors should be avoided if possible. If patients must be co-administered a strong CYP2C8 inhibitor, reduce the Xtandi dose to 80 mg once daily. If co-administration of the strong inhibitor is discontinued, the Xtandi dose should be returned to the dose used prior to initiation of the strong CYP2C8 inhibitor [see Drug Interactions (7.1) and Clinical Pharmacology (12.3)].
Dosage Forms and Strengths
Xtandi 40 mg capsules are white to off-white oblong soft gelatin capsules imprinted in black ink with MDV.
Contraindications
Pregnancy
Xtandi can cause fetal harm when administered to a pregnant woman based on its mechanism of action. Xtandi is not indicated for use in women. Xtandi is contraindicated in women who are or may become pregnant. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, apprise the patient of the potential hazard to the fetus and the potential risk for pregnancy loss [see Use in Specific Populations (8.1)].
Warnings and Precautions
Seizure
In the randomized clinical trial, 7 of 800 (0.9%) patients treated with Xtandi 160 mg once daily experienced a seizure. No seizures occurred in patients treated with placebo. Seizures occurred from 31 to 603 days after initiation of Xtandi. Patients experiencing seizure were permanently discontinued from therapy and all seizures resolved. There is no clinical trial experience re-administering Xtandi to patients who experienced seizures.
The safety of Xtandi in patients with predisposing factors for seizure is not known because these patients were excluded from the trial. These exclusion criteria included a history of seizure, underlying brain injury with loss of consciousness, transient ischemic attack within the past 12 months, cerebral vascular accident, brain metastases, brain arteriovenous malformation or the use of concomitant medications that may lower the seizure threshold.
Because of the risk of seizure associated with Xtandi use, patients should be advised of the risk of engaging in any activity where sudden loss of consciousness could cause serious harm to themselves or others.
Adverse Reactions
The following is discussed in more detail in other sections of the labeling:
•Seizure [see Warnings and Precautions (5.1)]
Clinical Trial Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
In the randomized clinical trial in patients with metastatic castration-resistant prostate cancer who had previously received docetaxel, patients received Xtandi 160 mg orally once daily (N = 800) or placebo (N = 399). The median duration of treatment was 8.3 months with Xtandi and 3.0 months with placebo. All patients continued androgen deprivation therapy. Patients were allowed, but not required, to take glucocorticoids. During the trial, 48% of patients on the Xtandi arm and 46% of patients on the placebo arm received glucocorticoids. All adverse events and laboratory abnormalities were graded using NCI CTCAE version 4.
The most common adverse drug reactions (≥ 5%) reported in patients receiving Xtandi in the randomized clinical trial were asthenia/fatigue, back pain, diarrhea, arthralgia, hot flush, peripheral edema, musculoskeletal pain, headache, upper respiratory infection, muscular weakness, dizziness, insomnia, lower respiratory infection, spinal cord compression and cauda equina syndrome, hematuria, paresthesia, anxiety, and hypertension. Grade 3 and higher adverse reactions were reported among 47% of Xtandi-treated patients and 53% of placebo-treated patients. Discontinuations due to adverse events were reported for 16% of Xtandi-treated patients and 18% of placebo-treated patients. The most common adverse reaction leading to treatment discontinuation was seizure, which occurred in 0.9% of the Xtandi-treated patients compared to none (0%) of the placebo-treated patients. Table 1 shows adverse reactions reported in the randomized clinical trial that occurred at a ≥ 2% absolute increase in frequency in the Xtandi arm compared to the placebo arm.
Laboratory Abnormalities
In the randomized clinical trial, Grade 1-4 neutropenia occurred in 15% of patients on Xtandi (1% Grade 3-4) and in 6% of patients on placebo (no Grade 3-4). The incidence of Grade 1-4 thrombocytopenia was similar in both arms; 0.5% of patients on Xtandi and 1% on placebo experienced Grade 3-4 thrombocytopenia. Grade 1-4 elevations in ALT occurred in 10% of patients on Xtandi (0.3% Grade 3-4) and 18% of patients on placebo (0.5% Grade 3-4). Grade 1-4 elevations in bilirubin occurred in 3% of patients on Xtandi and 2% of patients on placebo.
Infections
In the randomized clinical trial, 1.0% of patients treated with Xtandi compared to 0.3% of patients on placebo died from infections or sepsis. Infection-related serious adverse events were reported in approximately 6% of the patients on both treatment arms.
Falls and Fall-related Injuries
In the randomized clinical trial, falls or injuries related to falls occurred in 4.6% of patients treated with Xtandi compared to 1.3% of patients on placebo. Falls were not associated with loss of consciousness or seizure. Fall-related injuries were more severe in patients treated with Xtandi and included non-pathologic fractures, joint injuries, and hematomas.
Hallucinations
In the randomized clinical trial, 1.6% of patients treated with Xtandi were reported to have Grade 1 or 2 hallucinations compared to 0.3% of patients on placebo. Of the patients with hallucinations, the majority were on opioid-containing medications at the time of the event. Hallucinations were visual, tactile, or undefined.
Drug Interactions
Drugs that Inhibit or Induce CYP2C8
Co-administration of a strong CYP2C8 inhibitor (gemfibrozil) increased the composite area under the plasma concentration-time curve (AUC) of enzalutamide plus N-desmethyl enzalutamide in healthy volunteers. Co-administration of Xtandi with strong CYP2C8 inhibitors should be avoided if possible. If co-administration of Xtandi with a strong CYP2C8 inhibitor cannot be avoided, reduce the dose of Xtandi [see Dosage and Administration (2.2) and Clinical Pharmacology (12.3)].
The effects of CYP2C8 inducers on the pharmacokinetics of enzalutamide have not been evaluated in vivo. Co-administration of Xtandi with strong or moderate CYP2C8 inducers (e.g., rifampin) may alter the plasma exposure of Xtandi and should be avoided if possible. Selection of a concomitant medication with no or minimal CYP2C8 induction potential is recommended [see Clinical Pharmacology (12.3)].
Drugs that Inhibit or Induce CYP3A4
Co-administration of a strong CYP3A4 inhibitor (itraconazole) increased the composite AUC of enzalutamide plus N-desmethyl enzalutamide by 1.3 fold in healthy volunteers [see Clinical Pharmacology (12.3)].
The effects of CYP3A4 inducers on the pharmacokinetics of enzalutamide have not been evaluated in vivo. Co-administration of Xtandi with strong CYP3A4 inducers (e.g., carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine) may decrease the plasma exposure of Xtandi and should be avoided if possible. Selection of a concomitant medication with no or minimal CYP3A4 induction potential is recommended. Moderate CYP3A4 inducers (e.g., bosentan, efavirenz, etravirine, modafinil, nafcillin) and St. John’s Wort may also reduce the plasma exposure of Xtandi and should be avoided if possible [see Clinical Pharmacology (12.3)].
Effect of Xtandi on Drug Metabolizing Enzymes
Enzalutamide is a strong CYP3A4 inducer and a moderate CYP2C9 and CYP2C19 inducer in humans. At steady state, Xtandi reduced the plasma exposure to midazolam (CYP3A4 substrate), warfarin (CYP2C9 substrate), and omeprazole (CYP2C19 substrate). Concomitant use of Xtandi with narrow therapeutic index drugs that are metabolized by CYP3A4 (e.g., alfentanil, cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus and tacrolimus), CYP2C9 (e.g., phenytoin, warfarin) and CYP2C19 (e.g., S-mephenytoin) should be avoided, as enzalutamide may decrease their exposure. If co-administration with warfarin cannot be avoided, conduct additional INR monitoring [see Clinical Pharmacology (12.3)].
USE IN SPECIFIC POPULATIONS
Pregnancy
Pregnancy Category X[see Contraindications (4)].
Xtandi can cause fetal harm when administered to a pregnant woman based on its mechanism of action. While there are no human or animal data on the use of Xtandi in pregnancy and Xtandi is not indicated for use in women, it is important to know that maternal use of an androgen receptor inhibitor could affect development of the fetus. Xtandi is contraindicated in women who are or may become pregnant while receiving the drug. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, apprise the patient of the potential hazard to the fetus and the potential risk for pregnancy loss. Advise females of reproductive potential to avoid becoming pregnant during treatment with Xtandi.
Nursing Mothers
Xtandi is not indicated for use in women. It is not known if enzalutamide is excreted in human milk. Because many drugs are excreted in human milk, and because of the potential for serious adverse reactions in nursing infants from Xtandi, a decision should be made to either discontinue nursing, or discontinue the drug taking into account the importance of the drug to the mother.
Pediatric Use
Safety and effectiveness of Xtandi in pediatric patients have not been established.
Geriatric Use

Of 800 patients who received Xtandi in the randomized clinical trial, 71 percent were 65 and over, while 25 percent were 75 and over. No overall differences in safety or effectiveness were observed between these patients and younger patients. Other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
Patients with Renal Impairment
A dedicated renal impairment trial for Xtandi has not been conducted. Based on the population pharmacokinetic analysis using data from clinical trials in patients with metastatic castration-resistant prostate cancer and healthy volunteers, no significant difference in enzalutamide clearance was observed in patients with pre-existing mild to moderate renal impairment (30 mL/min ≤ creatinine clearance [CrCL] ≤ 89 mL/min) compared to patients and volunteers with baseline normal renal function (CrCL ≥ 90 mL/min). No initial dosage adjustment is necessary for patients with mild to moderate renal impairment. Severe renal impairment (CrCL < 30 mL/min) and end-stage renal disease have not been assessed [see Clinical Pharmacology (12.3)].
Patients with Hepatic Impairment
A dedicated hepatic impairment trial compared the composite systemic exposure of enzalutamide plus N-desmethyl enzalutamide in volunteers with baseline mild or moderate hepatic impairment (Child-Pugh Class A and B, respectively) versus healthy controls with normal hepatic function. The composite AUC of enzalutamide plus N-desmethyl enzalutamide was similar in volunteers with mild or moderate baseline hepatic impairment compared to volunteers with normal hepatic function. No initial dosage adjustment is necessary for patients with baseline mild or moderate hepatic impairment. Baseline severe hepatic impairment (Child-Pugh Class C) has not been assessed [see Clinical Pharmacology (12.3)].
Overdosage
In the event of an overdose, stop treatment with Xtandi and initiate general supportive measures taking into consideration the half-life of 5.8 days. In a dose escalation study, no seizures were reported at < 240 mg daily, whereas 3 seizures were reported, 1 each at 360 mg, 480 mg, and 600 mg daily. Patients may be at increased risk of seizures following an overdose.
Xtandi Description
Enzalutamide is an androgen receptor inhibitor. The chemical name is 4 - {3 - [4 - cyano - 3 - (trifluoromethyl)phenyl] - 5,5 - dimethyl - 4 - oxo - 2 - sulfanylideneimidazolidin - 1 - yl} - 2 - fluoro - N-methylbenzamide.
The molecular weight is 464.44 and molecular formula is C21H16F4N4O2S. The structural formula is:
Enzalutamide is a white crystalline non-hygroscopic solid. It is practically insoluble in water.
Xtandi is provided as liquid-filled soft gelatin capsules for oral administration. Each capsule contains 40 mg of enzalutamide as a solution in caprylocaproyl polyoxylglycerides. The inactive ingredients are caprylocaproyl polyoxylglycerides, butylated hydroxyanisole, butylated hydroxytoluene, gelatin, sorbitol sorbitan solution, glycerin, purified water, titanium dioxide, and black iron oxide.
Xtandi - Clinical Pharmacology
Mechanism of Action
Enzalutamide is an androgen receptor inhibitor that acts on different steps in the androgen receptor signaling pathway. Enzalutamide has been shown to competitively inhibit androgen binding to androgen receptors and inhibit androgen receptor nuclear translocation and interaction with DNA. A major metabolite, N-desmethyl enzalutamide, exhibited similar in vitro activity to enzalutamide. Enzalutamide decreased proliferation and induced cell death of prostate cancer cells in vitro, and decreased tumor volume in a mouse prostate cancer xenograft model.
Pharmacokinetics
The pharmacokinetics of enzalutamide and its major active metabolite (N-desmethyl enzalutamide) were evaluated in patients with metastatic castration-resistant prostate cancer and healthy male volunteers. The plasma enzalutamide pharmacokinetics are adequately described by a linear two-compartment model with first-order absorption.
Absorption
Following oral administration (Xtandi 160 mg daily) in patients with metastatic castration-resistant prostate cancer, the median time to reach maximum plasma enzalutamide concentrations (Cmax) is 1 hour (range 0.5 to 3 hours). At steady state, the plasma mean Cmax values for enzalutamide and N-desmethyl enzalutamide are 16.6 μg/mL (23% CV) and 12.7 μg/mL (30% CV), respectively, and the plasma mean predose trough values are 11.4 μg/mL (26% CV) and 13.0 μg/mL (30% CV), respectively.
With the daily dosing regimen, enzalutamide steady state is achieved by Day 28, and enzalutamide accumulates approximately 8.3-fold relative to a single dose. Daily fluctuations in enzalutamide plasma concentrations are low (mean peak-to-trough ratio of 1.25). At steady state, enzalutamide showed approximately dose proportional pharmacokinetics over the daily dose range of 30 to 360 mg.
A single 160 mg oral dose of Xtandi was administered to healthy volunteers with a high-fat meal or in the fasted condition. A high-fat meal did not alter the AUC to enzalutamide or N-desmethyl enzalutamide. The results are summarized in Figure 1.
Distribution and Protein Binding
The mean apparent volume of distribution (V/F) of enzalutamide in patients after a single oral dose is 110 L (29% CV).
Enzalutamide is 97% to 98% bound to plasma proteins, primarily albumin. N-desmethyl enzalutamide is 95% bound to plasma proteins.
Metabolism
Following single oral administration of 14C-enzalutamide 160 mg, plasma samples were analyzed for enzalutamide and its metabolites up to 77 days post dose. Enzalutamide, N-desmethyl enzalutamide, and a major inactive carboxylic acid metabolite accounted for 88% of the 14C-radioactivity in plasma, representing 30%, 49%, and 10%, respectively, of the total 14C-AUC0-inf.
In vitro, human CYP2C8 and CYP3A4 are responsible for the metabolism of enzalutamide. Based on in vivo and in vitro data, CYP2C8 is primarily responsible for the formation of the active metabolite (N-desmethyl enzalutamide).
Elimination
Enzalutamide is primarily eliminated by hepatic metabolism. Following single oral administration of 14C-enzalutamide 160 mg, 85% of the radioactivity is recovered by 77 days post dose: 71% is recovered in urine (including only trace amounts of enzalutamide and N-desmethyl enzalutamide), and 14% is recovered in feces (0.4% of dose as unchanged enzalutamide and 1% as N-desmethyl enzalutamide).
The mean apparent clearance (CL/F) of enzalutamide in patients after a single oral dose is 0.56 L/h (range 0.33 to 1.02 L/h).
The mean terminal half-life (t1/2) for enzalutamide in patients after a single oral dose is 5.8 days (range 2.8 to 10.2 days). Following a single 160 mg oral dose of enzalutamide in healthy volunteers, the mean terminal t1/2 for N-desmethyl enzalutamide is approximately 7.8 to 8.6 days.
Pharmacokinetics in Special Populations
Renal Impairment:
A population pharmacokinetic analysis (based on pre-existing renal function) was carried out with data from 59 healthy male volunteers and 926 patients with metastatic castration-resistant prostate cancer enrolled in clinical trials, including 512 with normal renal function (CrCL ≥ 90 mL/min), 332 with mild renal impairment (CrCL 60 to < 90 mL/min), 88 with moderate renal impairment (CrCL 30 to < 60 mL/min), and 1 with severe renal impairment (CrCL < 30 mL/min). The apparent clearance of enzalutamide was similar in patients with pre-existing mild and moderate renal impairment (CrCL 30 to < 90 mL/min) compared to patients and volunteers with normal renal function. The potential effect of severe renal impairment or end stage renal disease on enzalutamide pharmacokinetics cannot be determined as clinical and pharmacokinetic data are available from only one patient [see Use in Specific Populations (8.6)].
Hepatic Impairment:
The plasma pharmacokinetics of enzalutamide and N-desmethyl enzalutamide were examined in volunteers with normal hepatic function (N = 16) and with pre-existing mild (N = 8, Child-Pugh Class A) or moderate (N = 8, Child-Pugh B) hepatic impairment. Xtandi was administered as a single 160 mg dose. The composite AUC of enzalutamide plus N-desmethyl enzalutamide was similar in volunteers with mild or moderate baseline hepatic impairment compared to volunteers with normal hepatic function. The results are summarized in Figure 1. Clinical and pharmacokinetic data are not available for patients with severe hepatic impairment (Child-Pugh Class C) [see Use in Specific Populations (8.7)].
Body Weight and Age:
Population pharmacokinetic analyses showed that weight (range: 46 to 163 kg) and age (range: 41 to 92 yr) do not have a clinically meaningful influence on the exposure to enzalutamide.
Gender:
The effect of gender on the pharmacokinetics of enzalutamide has not been evaluated.
Race:
The majority of patients in the randomized clinical trial were Caucasian (> 92%). There are insufficient data to evaluate potential differences in the pharmacokinetics of enzalutamide in other races.
Drug Interactions
Effect of Other Drugs on Xtandi:
In a drug-drug interaction trial in healthy volunteers, a single 160 mg oral dose of Xtandi was administered alone or after multiple oral doses of gemfibrozil (strong CYP2C8 inhibitor). Gemfibrozil increased the AUC0-inf of enzalutamide plus N-desmethyl enzalutamide by 2.2-fold with minimal effect on Cmax. The results are summarized in Figure 1[see Dosage and Administration (2.2) and Drug Interactions (7.1)].
In a drug-drug interaction trial in healthy volunteers, a single 160 mg oral dose of Xtandi was administered alone or after multiple oral doses of itraconazole (strong CYP3A4 inhibitor). Itraconazole increased the AUC0-inf of enzalutamide plus N-desmethyl enzalutamide by 1.3-fold with no effect on Cmax. The results are summarized in Figure 1[see Dosage and Administration (2.2) and Drug Interactions (7.2)].
PK parameters (Cmax and AUC0-inf) are for enzalutamide plus N-desmethyl enzalutamide, except in the food-effect trial, where they are for enzalutamide alone. *See Dosage and Administration (2.2).
Effect of Xtandi on Other Drugs:
In an in vivo phenotypic cocktail drug-drug interaction trial in patients with castration-resistant prostate cancer, a single oral dose of the CYP probe substrate cocktail (for CYP2C8, CYP2C9, CYP2C19, and CYP3A4) was administered before and concomitantly with Xtandi (following at least 55 days of dosing at 160 mg daily). The results are summarized in Figure 2. Results showed that in vivo, at steady state, Xtandi is a strong CYP3A4 inducer and a moderate CYP2C9 and CYP2C19 inducer [see Drug Interactions (7.3)]. Xtandi did not cause clinically meaningful changes in exposure to the CYP2C8 substrate.
See Drug Interactions (7.3).
 In vitro, enzalutamide, N-desmethyl enzalutamide, and the major inactive carboxylic acid metabolite caused direct inhibition of multiple CYP enzymes including CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4/5; however, subsequent clinical data showed that Xtandi is an inducer of CYP2C9, CYP2C19, and CYP3A4 and had no clinically meaningful effect on CYP2C8 (see Figure 2). In vitro, enzalutamide caused time-dependent inhibition of CYP1A2.
In vitro studies showed that enzalutamide caused induction of CYP3A4 and that enzalutamide is not expected to induce CYP1A2 at therapeutically relevant concentrations.
In vitro, enzalutamide, N-desmethyl enzalutamide, and the major inactive carboxylic acid metabolite are not substrates for human P-glycoprotein. In vitro, enzalutamide and N-desmethyl enzalutamide are inhibitors of human P-glycoprotein, while the major inactive carboxylic acid metabolite is not.
Cardiac Electrophysiology
The effect of enzalutamide 160 mg/day at steady state on the QTc interval was evaluated in 796 patients with castration-resistant prostate cancer. No large difference (i.e., greater than 20 ms) was observed between the mean QT interval change from baseline in patients treated with Xtandi and that in patients treated with placebo, based on the Fridericia correction method. However, small increases in the mean QTc interval (i.e., less than 10 ms) due to enzalutamide cannot be excluded due to limitations of the study design.
Nonclinical Toxicology
Carcinogenesis, Mutagenesis, Impairment of Fertility
Long-term animal studies have not been conducted to evaluate the carcinogenic potential of enzalutamide.
Enzalutamide did not induce mutations in the bacterial reverse mutation (Ames) assay and was not genotoxic in either the in vitro mouse lymphoma thymidine kinase (Tk) gene mutation assay or the in vivo mouse micronucleus assay.
Based on nonclinical findings in repeat-dose toxicology studies, which were consistent with the pharmacological activity of enzalutamide, male fertility may be impaired by treatment with Xtandi. In a 26-week study in rats, atrophy of the prostate and seminal vesicles was observed at ≥ 30 mg/kg/day (equal to the human exposure based on AUC). In 4- and 13-week studies in dogs, hypospermatogenesis and atrophy of the prostate and epididymides were observed at ≥ 4 mg/kg/day (0.3 times the human exposure based on AUC).
Clinical Studies
The efficacy and safety of Xtandi in patients with metastatic castration-resistant prostate cancer who had received prior docetaxel-based therapy were assessed in a randomized, placebo-controlled, multicenter phase 3 clinical trial. The primary endpoint was overall survival. A total of 1199 patients were randomized 2:1 to receive either Xtandi orally at a dose of 160 mg once daily (N = 800) or placebo orally once daily (N = 399). All patients continued androgen deprivation therapy. Patients were allowed, but not required to continue or initiate glucocorticoids. Study treatment continued until disease progression (evidence of radiographic progression, a skeletal-related event, or clinical progression), initiation of new systemic antineoplastic treatment, unacceptable toxicity, or withdrawal. Patients with a history of seizure, taking medicines known to decrease the seizure threshold, or with other risk factors for seizure were not eligible [see Warnings and Precautions (5.1)].

The following patient demographics and baseline disease characteristics were balanced between the treatment arms. The median age was 69 years (range 41-92) and the racial distribution was 92.7% Caucasian, 3.9% Black, 1.1% Asian, and 2.1% Other. Ninety-two percent of patients had an ECOG performance status score of 0-1 and 28% had a mean Brief Pain Inventory score of ≥ 4. Ninety-one percent of patients had metastases in bone and 23% had visceral involvement in the lung and/or liver. Fifty-nine percent of patients had radiographic evidence of disease progression and 41% had PSA-only progression on study entry. All patients had received prior docetaxel-based therapy and 24% had received two cytotoxic chemotherapy regimens. During the trial, 48% of patients on the Xtandi arm and 46% of patients on the placebo arm received glucocorticoids.

The pre-specified interim analysis at the time of 520 events showed a statistically significant improvement in overall survival in patients on the Xtandi arm compared to patients on the placebo arm (Table 2 and Figure 3).

How Supplied/Storage and Handling
•Xtandi (enzalutamide) 40 mg capsules are supplied as white to off-white oblong soft gelatin capsules imprinted in black ink with MDV. Xtandi capsules are available in the following package sizes:
◦Bottles of 120 capsules (NDC 0469-0125-99)
Recommended storage: Store Xtandi capsules at 20°C to 25°C (68°F to 77°F) in a dry place and keep the container tightly closed. Excursions permitted from 15°C to 30°C (59°F to 86°F).

Patient Counseling Information
See FDA-approved patient labeling (PATIENT INFORMATION).

•Instruct patients to take their dose at the same time each day (once daily). Xtandi can be taken with or without food. Each capsule should be swallowed whole. Do not chew, dissolve, or open the capsules.
•Inform patients receiving a GnRH analog that they need to maintain this treatment during the course of treatment with Xtandi.
•Inform patients that Xtandi has been associated with an increased risk of seizure. Discuss conditions that may predispose to seizures and medications that may lower the seizure threshold. Advise patients of the risk of engaging in any activity where sudden loss of consciousness could cause serious harm to themselves or others.
•Inform patients that Xtandi may cause dizziness, mental impairment, paresthesia, hypoesthesia, and falls.
•Inform patients that they should not interrupt, modify the dose, or stop Xtandi without first consulting their physician. Inform patients that if they miss a dose, then they should take it as soon as they remember. If they forget to take the dose for the whole day, then they should take their normal dose the next day. They should not take more than their prescribed dose per day.
•Apprise patients of the common side effects associated with Xtandi: asthenia/fatigue, back pain, diarrhea, arthralgia, hot flush, peripheral edema, musculoskeletal pain, headache, upper respiratory infection, muscular weakness, dizziness, insomnia, lower respiratory infection, spinal cord compression and cauda equina syndrome, hematuria, paresthesia, anxiety, and hypertension. Direct the patient to a complete list of adverse drug reactions in PATIENT INFORMATION.
•Inform patients that Xtandi may be harmful to a developing fetus. Patients should also be informed that they should use a condom if having sex with a pregnant woman. A condom and another effective method of birth control should be used if the patient is having sex with a woman of child-bearing potential. These measures are required during and for three months after treatment with Xtandi.
How Supplied/Storage and Handling
•Xtandi (enzalutamide) 40 mg capsules are supplied as white to off-white oblong soft gelatin capsules imprinted in black ink with MDV. Xtandi capsules are available in the following package sizes:
◦Bottles of 120 capsules (NDC 0469-0125-99)
Recommended storage: Store Xtandi capsules at 20°C to 25°C (68°F to 77°F) in a dry place and keep the container tightly closed. Excursions permitted from 15°C to 30°C (59°F to 86°F).

恩杂鲁胺（XTANDI）有效降低转移性前列腺癌进展
恩杂鲁胺（XTANDI、enzalutamide）属于口服类雄激素受体拮抗剂，目前经临床研究及美国FDA（食品与药品监督局）批准，用于化疗后进展的转移性去势耐受前列腺癌的治疗（即前列腺癌患者经化疗后，肿瘤或癌症细胞仍然在生长的此类患者），可延长患者生存期。
美国健康与科学大学“奈特癌症研究所”Beer教授，目前进行了一项随机双盲3期前列腺癌患者试验，试验的结果发表在2014年7月31日出版的NEJM杂志上。在此次试验中，1700多名患者被随机分为恩杂鲁胺（XTANDI）组和安慰剂组，分别接受每日160mg的恩杂鲁胺（XTANDI）用药，或接受安慰剂治疗，复合终点为影像学无进展生存率和总生存率。
由于540名患者死亡时恩杂鲁胺（XTANDI）组的疗效优势已十分显著，故奈特癌症研究所的这一项研究被提前中止。数据表明，在实验进行12个月时，恩杂鲁胺（XTANDI）组前列腺癌细胞无进展生存率为65%，而安慰剂组仅为14%。在实验终止时，恩杂鲁胺（XTANDI）组存活人数为626人，占比72%，而安慰剂组存活532人，占比63%。从实验数据上来看，恩杂鲁胺（XTANDI）治疗化疗后进展的转移性前列腺癌中，无论是前列腺癌细胞的无进展生存率（65%比14%），还是总生存率（72%比63%），恩杂鲁胺（XTANDI）均显示出极为显著的优势。在细胞毒性化疗起始时间、首次骨相关事件出现时间、完全或部分软组织反应、前列腺特异抗原（PSA）增大时间、PSA下降的比例等等数据中，恩杂鲁胺（XTANDI）都表现出了治疗的优势。
但在目前，对于经雄激素阻断治疗失败后，未接受化疗的转移性前列腺癌患者，尚缺乏新的治疗手段。恩杂鲁胺（XTANDI）的主要副作用为高血压和疲乏。
综合上述，恩杂鲁胺（XTANDI）可有效降低转移性前列腺癌细胞的进展，减少死亡风险，延缓患者的化疗起始时间。
----------------------------------------
注：以下产品均可提供，购买时以咨询为准！
----------------------------------------
产地国家：法国
原产地英文商品名:
Xtandi 40mg/cap 112caps/box
原产地英文药品名:
ESCITALOPRAM
中文参考商品译名:
Xtandi 40毫克/胶囊 112胶囊/盒
中文参考药品译名:
生产厂家中文参考译名:
恩杂鲁胺
生产厂家英文名:
ASTELLAS

-------------------------------------------------------
产地国家：美国
原产地英文商品名:
Xtandi 40mg/cap 120caps/box
原产地英文药品名:
ESCITALOPRAM
中文参考商品译名:
Xtandi 40毫克/胶囊 120胶囊/瓶
中文参考药品译名:
生产厂家中文参考译名:
恩杂鲁胺
生产厂家英文名:
ASTELLAS

-------------------------------------------------------
产地国家：日本
原产地英文商品名:
Xtandi（イクスタンジカプセル）40mg/cap 56caps/box
原产地英文药品名:
ESCITALOPRAM
中文参考商品译名:
Xtandi（イクスタンジカプセル）40毫克/胶囊 56胶囊/盒
中文参考药品译名:
生产厂家中文参考译名:
恩杂鲁胺
生产厂家英文名:
ASTELLAS

-------------------------------------------------------
产地国家：英国
原产地英文商品名:
Xtandi 40mg/cap 112caps/box
原产地英文药品名:
ESCITALOPRAM
中文参考商品译名:
Xtandi 40毫克/胶囊 112胶囊/盒
中文参考药品译名:
生产厂家中文参考译名:
恩杂鲁胺
生产厂家英文名:
ASTELLAS