Prostate cancer (HSPC) is a common malignant tumor in elderly men, the second most common cancer in men in the world, the incidence in Europe and United States is extremely high, the incidence rate in elderly men is second only to lung cancer, in the mainland with the aging of the population and the improvement of living standards, the incidence and mortality rate of prostate cancer are on the rise.
According to data released by the World Health Organization's International Agency for Research on Cancer, there were more than 1.41 million new cases of prostate cancer in the world and 115,000 new cases of prostate cancer in China in 2020. Prostate cancer is one of the common malignant tumors in men, and endocrine therapy is a commonly used treatment for prostate cancer.
Treatment options for mHSPC and mCRPC
What are the oral medications for hormone therapy for prostate cancer?
Hormone therapy, also known as endocrine therapy, is an important and effective means of prostate cancer treatment. Prostate cancer cells rely on androgens for growth, and cutting off the supply of androgens can cause cancer cells to grow more slowly or die.
First-generation antiandrogens: bicalutamide
Second-generation antiandrogens: enzalutamide, apalutamide, revilutamide
Third-generation androgen synthesis inhibitors: abiraterone, darolutamide
1、比卡鲁胺(Bicalutamide)
Steroid inhibitors, which can block the adrenal glands from synthesizing androgens, thereby inhibiting the production and action of androgens. As a first-generation antiandrogen, drug resistance develops after prolonged use.
Medical insurance reimbursement indications/medical insurance reimbursement conditions: medical insurance category B. It is indicated for the treatment of advanced prostate cancer in combination with luteinizing hormone-releasing hormone (LHRH) analogues or surgical orchiectomy.
Price before medical insurance reimbursement: between 185 yuan and 1800 yuan
Dosage: Adults: Adult males including the elderly: One tablet (50 mg) once a day, should be started at the same time as treatment with LHRH analogues or surgical orchiectomy.
2、恩杂鲁胺（恩扎卢胺、Enzalutamide）
Enzalutamide is a second-generation AR inhibitor approved by the FDA in 2012 for patients with CRPC, and the NMPA has also approved it for the treatment of adult patients with asymptomatic or mildly symptomatic metastatic castration-resistant prostate cancer (mCRPC) who are not receiving chemotherapy after ADT treatment failure.
It has a high affinity for the LBD of AR and reduces intratumor androgen levels by binding to AR, inhibiting the transport of AR to the nucleus and binding to DNA. Therefore, it is not only an antagonist of androgen receptors, but also has an inhibitory effect on androgen signaling pathways.
Medical insurance reimbursement indications/medical insurance reimbursement conditions: medical insurance category B. It is suitable for prostate cancer patients who have been previously treated with docetaxel and who are castration-tolerant for metastases.
Price before reimbursement by Medicare:
1. Enzalutamide soft capsule (Pletan/Hausen): The specification is 40mg, 14 capsules, 2 plates, and the price is about ¥1150 yuan/box.
2. Enzalutamide soft capsules (Ancortan): The specification is 40mg*112 capsules, and the price varies in different pharmacies, about ¥4600/box to ¥7568/box.
3. India version of enzalutamide: the price is relatively low, about 1500 yuan a bottle (specification is 40mg*112 tablets)
Dosage: 160mg, oral administration, 1 time a day. Swallow the capsule whole. Do not chew, dissolve, or open capsules. May be taken with or without food.
3、阿帕他胺（阿帕鲁胺、Apalutamide）
Apalutamide is an androgen receptor (AR) inhibitor that helps block the activity of male hormones, such as testosterone, and is primarily used to treat hormone-sensitive prostate cancer (mHSPC).
Enzalutamide can be used for metastatic cancers (cancers that have spread to other parts of the body) for non-metastatic cancers, whereas apalutamide is commonly used for non-metastatic cancers.
Medical insurance reimbursement indications/medical insurance reimbursement conditions: medical insurance category B
Limitations: 1. Adult patients with metastatic endocrine therapy-sensitive prostate cancer (mHSPC);
2. Adult patients with non-metastatic castration-resistant prostate cancer (NM-CRPC) at high risk of metastasis.
Price before medical insurance reimbursement: At present, the domestic price of apalutamide (original research) of Xi'an Janssen is 120 tablets/5808 yuan, equivalent to 48.4 yuan per tablet.
Dosage: The recommended dose of this product is 240mg (4 tablets of 60mg), once daily, oral administration. Swallow whole. Can be taken alone or with food.
4、瑞维鲁胺（艾瑞恩、Rezvilutamide、SHR3680）
Revilutamide was approved in China for the treatment of metastatic hormone-sensitive prostate cancer (mHSPC) with high tumor burden.
According to Hengrui Pharmaceutical's public information, SHR3680 is a second-generation androgen receptor (AR) inhibitor independently developed by the company. Its innovative molecular structure introduces a dihydroxyl group to improve hydrophilicity, with higher plasma exposure and lower blood-brain barrier transmittance. The Phase I/II study demonstrated that revilutamide was well tolerated and safe, with good anti-tumor activity at all doses in clinical trials in patients with mCRPC.
Indications for medical insurance reimbursement/medical insurance reimbursement conditions: medical insurance category B, limited to patients with metastatic hormone-sensitive prostate cancer (mHSPC).
Price before reimbursement by medical insurance: 6200 yuan/box (80mg/tablet, 21 tablets/plate, 4 plates/box)
Dosage: The recommended dose is 240mg/time, once a day, orally, swallowed whole, after a meal or on an empty stomach.
5、阿比特龙（Abirateroneacetate）
Another drug approved by the FDA for the treatment of patients with all stages of mCRPC is abirateroneacetate, an androgen synthesis inhibitor.
CYP17A1 has 17α-hydroxylase and 17,20-lyase catalytic activity, and is essential for the production of androgens and glucocorticoids, abiraterone promotes apoptosis of prostate tumor cells by inhibiting the activity of rate-limiting enzyme CYP17A1 of androgen synthesis, blocking all androgens from three sources: testicles, adrenal glands, and tumor cells themselves.
Indications for reimbursement by medical insurance/reimbursement conditions under medical insurance: Category B of medical insurance, suitable for the treatment of patients with castration-refractory prostate cancer (CRPC) who have been metastasized by previous paclitaxel-containing chemotherapy with polyene-paclitaxel.
Price: Zhengda Tianqing (1280 yuan/box/bottle), Shengdi Pharmaceutical (717.6 yuan/bottle), Shanxiang Pharmaceutical (717.6 yuan/bottle), Qilu Pharmaceutical (651.6 yuan/bottle), Zhendong Pharmaceutical (1550.0 yuan/bottle) and Dr.Reddy's Laboratories Limited (976.0 yuan/bottle, 0.25g*120 tablets).
Dosage: The recommended dose of this product is 1000 mg (4x250 mg tablets) orally once daily, combined with prednisone 5 mg orally twice daily.
6、达罗他胺（Darolutamide）
Darolutamide is an androgen receptor inhibitor (ARi) primarily used for the treatment of adult patients with non-metastatic castration-resistant prostate cancer (NM-CRPC) at high risk of metastasis. This drug has a high affinity for androgen receptors through a unique chemical structure, which strongly inhibits the function of the receptors and the growth of prostate cancer cells.
The clinical application of darolutamide has been widely recognized, especially in clinical trials such as ARAMIS, which has shown significant efficacy, which can prolong the metastasis-free survival of patients.
Medical insurance reimbursement indications/medical insurance reimbursement conditions: medical insurance category B,
Limitations: 1. Treatment of adult patients with non-metastatic castration-resistant prostate cancer (NM-CRPC) at high risk of metastasis; 2. Combined with docetaxel for the treatment of adult patients with metastatic hormone-sensitive prostate cancer (mHSPC).
Price before reimbursement by medical insurance: 300mg*120 tablets, ¥7850/box
Dosage: The recommended dose is darolutamide 600 mg (two 300 mg film-coated tablets) orally twice daily, equivalent to a total daily dose of 1200 mg.
How effective are new endocrine therapy drugs for prostate cancer?
Efficacy of enzalutamide compared with bicalutamide, apalutamide, revilutamide and abiraterone:
How to choose new endocrine therapy drugs for prostate cancer?
- Apalutamide and enzalutamide are equally effective, but enzalutamide has a very specific side effect, epilepsy, which is much more common than apalutamide. Clinical experiments have proved that after taking the drug, the concentration of apalutamide that enters the blood-brain barrier is much lower than the concentration of enzalutamide, and epilepsy generally does not occur under normal medication. Therefore, when using enzalutamide, more attention should be paid to the concentration of the drug, and more attention must be paid to prevent omission and overdose;
- As a first-generation anti-androgen, bicalutamide is inferior to the second-generation in terms of safety and efficacy.
- Enzalutamide and abiraterone are both hormonal therapies used to treat advanced prostate cancer.
- If the patient's cancer has spread to the liver or lungs, or if the patient cannot take steroids, enzalutamide is a better option than abiraterone. Because abiraterone has to be taken with steroids.
- However, abiraterone is a better choice than enzalutamide if the patient has epilepsy or is at risk of seizures, tiredness (fatigue), memory or concentration problems. Enzalutamide increases the risk of these problems. Enzalutamide is easier to take than abiraterone, without fasting and without taking steroids.