Which medications are used in the treatment of metastatic and advanced prostate cancer?

Updated: Dec 29, 2020
  • Author: Martha K Terris, MD, FACS; Chief Editor: Edward David Kim, MD, FACS  more...
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Answer

Gonadotropin-releasing hormone (GnRH) analogues (eg, leuprolide) suppress ovarian and testicular steroidogenesis by decreasing luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels, whereas GnRH antagonists (eg, relugolixdegarelix) lower serum testosterone levels by suppressing LH and FSH.

Bisphosphonates are analogues of pyrophosphate that act by binding to hydroxyapatite in bone matrix, thereby inhibiting the dissolution of crystals. These agents prevent osteoclast attachment to the bone matrix and osteoclast recruitment and viability. [16]

Antiandrogens are used as combination agents to treat prostate cancer. Antifungal agents produce a response similar to that of antiandrogens. These drugs inhibit various cytochrome P-450 enzymes, including 11-beta-hydroxylase and 17-alpha-hydroxylase, which in turn inhibit steroid synthesis. The antiandrogen abiraterone (Zytiga) is a 17 alpha-hydroxylase/C17, 20-lyase inhibitor that was approved by the US Food and Drug Administration (FDA) in 2011 for use in combination with prednisone for treatment of metastatic castration-resistant prostate cancer (mCRPC) in patients who received prior chemotherapy containing docetaxel. [17]

An ultramicronized abiraterone tablet (Yonsa) was approved in May 2018 for CRPC in combination with methylprednisolone. The ultramicronized formulation may be administered with or without food, whereas, the original tablet formulation (Zytiga) must be administered 1 hour before or 2 hours after meals.

In 2012, the FDA expanded approval of abiraterone with prednisone for chemotherapy-naïve patients with mCRPC. Approval was based on the results of a study of 1088 men in which patients who received abiraterone had a median overall survival of 35.3 months compared with 30.1 months for those receiving the placebo. Abiraterone also improved radiographic progression-free survival (rPFS). The median rPFS was 8.3 months in the placebo group and had not yet been reached for patients treated with abiraterone at the time of analysis. [18]

In February 2018, the FDA further expanded the approval for abiraterone for men with metastatic high-risk castration-sensitive prostate cancer (mCSPC). The new approval was based on the results of the 1199-patient LATITUDE trial. In the trial, patients were randomly assigned to receive either abiraterone and prednisone daily, along with standard androgen-deprivation therapy (ADT), or ADT alone. At 30.4 months of median follow-up, overall survival was not estimable in patients who were treated with abiraterone compared with 34.7 months in those who received placebo. Median time to initiation of chemotherapy was also not reached in the abiraterone arm compared with 38.9 months in the placebo arm. [19]

Chemotherapy agents inhibit cell growth and proliferation. Prostate cancer has been considered essentially a chemoresistant disease because of the poor survival outcomes reported in earlier series. No single agent has resulted in an objective response rate of greater than 30%. Because of the availability of prostate-specific antigen (PSA) testing to monitor the disease, renewed interest has been generated in this regard, and clinical trials are being conducted.

Corticosteroids have anti-inflammatory properties and cause profound and varied metabolic effects. These agents modify the body's immune response to diverse stimuli and are used in combination with agents such as mitoxantrone.

Immunologic agents are used as an autologous cellular immunotherapy designed to stimulate a patient’s own immune system to respond against the cancer.


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