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      News & Perspective Drugs & Diseases CME & Education Academy Video Decision Point
      Drugs & Diseases > Urology

      Prostate Cancer Medication

      Updated: Sep 07, 2023
      • Author: Chad R Tracy, MD; Chief Editor: Edward David Kim, MD, FACS  more...
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      Medication

      Medication Summary

      The goals of pharmacotherapy for prostate cancer are to induce remission, reduce morbidity, and prevent complications. Agents used include the following:

      • Androgen antagonists
      • Gonadotropin-releasing hormone (GnRH) agonists
      • GnRH antagonists
      • Bisphosphonates
      • Antifungal agents
      • Chemotherapeutic agents
      • Corticosteroids
      • Immunologic agents
      • Poly(ADP)-ribose polymerase (PARP) inhibitors
      • Radiopharmaceuticals
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      Antineoplastics, GnRH Agonist

      Class Summary

      GnRH agonists provide medical castration in patients with prostate cancer. They are used early and late in the course of the disease.

      GnRH agonists bind to the GnRH receptors on pituitary gonadotropin-producing cells, causing an initial release of luteinizing hormone (LH) and follicle stimulating hormone (FSH) and consequently a rise in testosterone levels for a few weeks. However, sustained use of these agents causes a decrease in the production of LH and FSH, which in turn leads to a decrease in testosterone production in the testes, reducing testosterone to castrate levels or to below the castrate threshold (50 ng/dL).

      Leuprolide (Lupron Depot, Lupron Depot-Ped, Eligard)

      Leuprolide is indicated as palliative treatment for advanced prostate cancer when orchiectomy or estrogen administration is not indicated or is unacceptable to the patient. It is a potent inhibitor of gonadotropin secretion when given continuously in therapeutic doses.

      Leuprolide can be administered as a depot at doses of 3.75 mg every 4 weeks, 11.25 mg every 12 weeks, or 30 mg every 24 weeks. Lupron should be administered intramuscularly, and Eligard should be administered subcutaneously.

      Triptorelin (Trelstar, Trelstar Mixject)

      Triptorelin is indicated for palliative treatment of advanced prostate cancer. The recommended dosage is 3.75 mg intramuscularly once every 4 weeks, 11.25 mg intramuscularly once every 12 weeks, or 22.5 mg intramuscularly once every 24 weeks.

      Triptorelin is a synthetic decapeptide agonist analogue of GnRH. It decreases LH and FSH secretion when administered long-term and thus decreases testosterone and estrogen levels. The serum testosterone concentration drops to a level typically seen in surgically castrated men.

      Histrelin (Vantas, Supprelin LA)

      Histrelin is indicated for the palliative treatment of advanced prostate cancer. It is available in a 50 mg subcutaneous implant designed to provide continuous release of histrelin at a nominal rate of 50-60 mcg/day over 12 months. This agent is not active when given orally. The recommended dose is 1 implant inserted subcutaneously every 12 months.

      Histrelin is a potent inhibitor of gonadotropin secretion. It desensitizes the responsiveness of pituitary gonadotropin, which in turn causes a reduction in testicular steroidogenesis.

      Goserelin (Zoladex)

      Goserelin is used in the palliative treatment of advanced prostate cancer. It is available as a 3.6 mg and 10.8 mg subcutaneous implant. The usual dose is 3.6 mg every 4 weeks or 10.8 mg every 12 weeks.

      Goserelin is a synthetic decapeptide analogue of GnRH that inhibits pituitary gonadotropin secretion if administered long-term. Like other GnRH agonists, goserelin provides a medical castration that deprives hormonally-dependent tumors of testosterone or estrogen. Decreased testosterone production leads to a decrease in prostatic size and improves associated symptoms.

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      Antineoplastics, Antiandrogen

      Class Summary

      Antiandrogens bind to androgen receptors and competitively inhibit their interaction with testosterone and dihydrotestosterone. Unlike medical castration, antiandrogens do not decrease LH levels and androgen production; testosterone levels are normal or increased. Antiandrogens are not commonly used as monotherapy. Rather, these agents are generally used in combination with a GnRH agonist.

      Antiandrogen therapy appears to be less effective than medical or surgical castration, except possibly in patients without overt metastases (M0). [230]

      Abiraterone (Yonsa, Zytiga)

      Abiraterone is indicated in combination with corticosteroids for the treatment of patients with metastatic castration-resistant prostate cancer (CRPC) and metastatic high-risk castration-sensitive prostate cancer (CSPC). Two products are available (tablet or ultramicronized tablet) with different dosage regimens.

      Abiraterone is an androgen biosynthesis inhibitor that inhibits 17-alpha-hydroxylase/C17,20-lyase (CYP17); this enzyme is expressed in testicular, adrenal, and prostatic tumor tissues and is required for androgen biosynthesis.

      Niraparib/abiraterone (Akeega)

      Fixed-dose combination of a poly (ADP-ribose) polymerase (PARP) inhibitor (niraparib) and antiandrogen (abiraterone) given with prednisone for deleterious or suspected deleterious BRCA-mutated mCRPC. 

      Bicalutamide (Casodex)

      Bicalutamide is indicated for the treatment of stage D2 metastatic carcinoma of the prostate, in combination with an LHRH analogue. It is a nonsteroidal androgen receptor inhibitor that competitively inhibits the action of androgens by binding to cytosol androgen receptors. The usual dosage is 50 mg orally once daily in the morning or evening.

      Flutamide

      Flutamide is approved by the US Food and Drug Administration (FDA) for use in combination with LHRH agonists for the management of locally confined stage B2-C and stage D2 metastatic prostate cancer. The usual dosage is 250 mg every 8 hours. The antiandrogenic effects of flutamide are mediated by the inhibition of the uptake and/or nuclear binding of testosterone and dihydrotestosterone by prostatic tissue. Flutamide-induced inhibition of androgens at the cellular level complements the castration effects of LHRH agonists.

      Nilutamide (Nilandron)

      Nilutamide is not suitable for inducing chemical castration since, by blocking the feedback mechanism for control of testosterone secretion, it increases testosterone concentrations. Instead, it is indicated for use in combination with surgical castration for the treatment of metastatic prostate cancer (stage D2). The initial dose is 300 mg once daily for 30 days. The maintenance dose for nilutamide is 150 mg once daily.

      Enzalutamide (Xtandi)

      Androgen receptor inhibitor; competitively inhibits androgen binding to androgen receptors; also inhibits androgen receptor nuclear translocation and interaction with DNA resulting in decreased proliferation and induced cell death.

      Major metabolite, N-desmethyl enzalutamide, exhibited similar in vitro activity to enzalutamide. It is indicated for treatment of nonmetastatic or metastatic castration-resistant prostate cancer (mCRPC). It is also approved for metastatic castration-sensitive prostate cancer (mCSPC).

      Apalutamide (Erleada)

      Androgen receptor (AR) inhibitor that binds directly to the ligand-binding domain of the AR. Inhibits AR nuclear translocation, inhibits DNA binding, and impedes AR-mediated transcription. This results in decreased tumor cell proliferation and increased apoptosis, leading to decreased tumor volume. It is indicated for nonmetastatic, castration-resistant prostate cancer (nmCRPC) and also for metastatic castration-sensitive prostate cancer (mCSPC).

      Darolutamide (Nubeqa)

      Darolutamide is an androgen receptor (AR) inhibitor. Darolutamide competitively inhibits androgen binding, AR nuclear translocation, and AR-mediated transcription. Keto-darolutamide, a major metabolite, exhibited similar in vitro activity to darolutamide. In addition, darolutamide functioned as a progesterone receptor (PR) antagonist in vitro. Darolutamide decreased prostate cancer cell proliferation in vitro and tumor volume in mouse xenograft models of prostate cancer. It is indicated for patients with nonmetastatic castration-resistant prostate cancer.

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      Antineoplastics, GnRH Antagonist

      Relugolix (Orgovyx)

      Indicated for advanced prostate cancer. Blocking GnRH receptors decreases the release of gonadotropins (ie, luteinizing hormone, follicle stimulating hormone), thereby decreasing the downstream production of testosterone by the testes in men. Available as an oral tablet. 

      Degarelix (Firmagon)

      Degarelix is a GnRH receptor antagonist indicated for patients with advanced prostate cancer. A single dose of degarelix 240 mg causes a decrease in the plasma concentrations of LH and FSH and subsequently of testosterone. Degarelix is effective in achieving and maintaining testosterone suppression below the castration level of 50 ng/dL. Unlike GnRH agonists, degarelix does not cause any short-term increase in testosterone; testosterone suppression to castrate concentrations is achieved within 1-3 days of administration.

      The initial dose is 240 mg subcutaneous injection (given as 2 injections of 120 mg at a concentration of 40 mg/mL). The maintenance dose is 80 mg subcutaneous injection (at a concentration of 20 mg/mL) every 28 days. The first maintenance dose should be given 28 days after the starting dose.

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      Antineoplastics, Antimicrotubular

      Class Summary

      Antimicrotubule chemotherapy agents such as docetaxel and cabazitaxel have demonstrated improvements in overall survival in patients with metastatic, castrate-resistant prostate cancer.

      Docetaxel (Docefrez, Taxotere)

      Docetaxel is indicated in combination with prednisone for the treatment of patients with androgen-independent (hormone-refractory), metastatic prostate cancer. The usual dose is 75 mg/m2 every 3 weeks as a 1-hour infusion in combination with prednisone 5 mg orally twice daily.

      Cabazitaxel (Jevtana)

      Cabazitaxel is indicated in combination with prednisone for hormone-refractory, metastatic prostate cancer previously treated with a docetaxel-containing regimen. The usual dosage is 25 mg/m2 administered as a 1-hour intravenous infusion every 3 weeks in combination with oral prednisone 10 mg administered daily throughout cabazitaxel treatment. Dosage can be reduced to 20 mg/m2 if patients experience adverse reactions. Caution should be used, since neutropenic deaths and severe hypersensitivity reactions have been reported.

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      Antineoplastics, Anthracenedione

      Class Summary

      For symptomatic patients who cannot tolerate docetaxel, mitoxantrone may provide palliative benefit. [230] Mitoxantrone is a palliative treatment option for patients who may not be candidates for taxane-based regimens.

      Mitoxantrone

      Mitoxantrone is indicated as initial chemotherapy for the treatment of patients with pain related to advanced, hormone-refractory prostate cancer. This agent is a palliative treatment that improves quality of life in these cases but does not improve survival. It is given in combination with corticosteroids such as prednisone. The recommended dose is 12-14 mg/m2 given as a short intravenous infusion every 21 days.

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      Antineoplastics, Hormones

      Class Summary

      Estramustine is a conjugate of an alkylating agent to estradiol. As a single agent, estramustine showed some activity in men with castrate-resistant prostate cancer, which led to its evaluation in various combination regimens. [231]

      Estramustine (Emcyt)

      Estramustine combines estradiol and nitrogen mustard. It is a relatively weak alkylating agent with weak estrogenic activity.

      Estramustine is used in combination with vinblastine, etoposide, paclitaxel, docetaxel, mitoxantrone, or corticosteroids to achieve synergistic effects. It is indicated for palliative treatment of metastatic and/or progressive carcinoma of the prostate. The usual dose is 14 mg/kg/day given in 3 or 4 divided doses. Treat patients for 30-90 days before assessing the possible benefits of continued therapy. Therapy should be continued as a favorable response is seen.

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      Chemotherapy Modulating Agents

      Class Summary

      Autologous cellular immunotherapy is designed to stimulate a patient’s own immune system to respond against the cancer. Sipuleucel-T was developed to induce an immune response targeted against prostatic acid phosphatase (PAP), an antigen that is expressed in most prostate cancers.

      Sipuleucel-T (Provenge)

      Sipuleucel-T is a cellular immunotherapy indicated for the treatment of asymptomatic or minimally symptomatic metastatic prostate cancer that is resistant to standard hormone treatment. It is an autologous treatment, and thus must be prepared individually for each patient.

      The usual regimen consists of the administration of 3 complete doses, given at intervals of approximately 2 weeks. Each dose contains a minimum of 50 million autologous CD54+ cells activated with prostatic acid phosphatase (PAP), an antigen expressed in more than 95% of prostate cancers, and granulocyte-macrophage colony-stimulating factor (GM-CSF), an immune-cell activator, suspended in 250 mL of lactated Ringer solution.

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      Antineoplastics, PARP Inhibitors

      Class Summary

      Advanced stages of prostate cancer may exhibit dysregulation of DNA-damage repair (DDR) pathways. These tumors are sensitive to poly(ADP) ribose polymerase (PARP) inhibition.

      Rucaparib (Rubraca)

      Indicated for deleterious BRCA mutation (germline and/or somatic) associated metastatic castration-resistant prostate cancer (mCRPC) in patients who have been treated with androgen receptor directed therapy and a taxane-based chemotherapy.

      Olaparib (Lynparza)

      Indicated for deleterious or suspected deleterious germline or somatic homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC) in adults who have progressed following prior treatment with enzalutamide or abiraterone.

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      Bisphosphonate Derivatives

      Class Summary

      In men with castrate-resistant prostate cancer and bone metastases, zoledronic acid is recommended to help prevent or delay disease-associated, skeletally related events. Skeletally related events can include pathologic fractures or spinal cord compression, which may require surgery or radiation therapy to bone. [232]

      Zoledronic acid (Zometa)

      Zoledronic acid is an intravenous bisphosphonate that is indicated for patients with documented bone metastases from solid tumors treated with standard chemotherapy. Prostate cancer should have progressed after treatment with at least 1 hormonal therapy. It inhibits bone resorption, possibly by acting on osteoclasts or osteoclast precursors, and thus reduces the risk of skeletally related events. Adverse effects include osteonecrosis of the jaw.

      General dosing recommendations include administering 4 mg infused intravenously over no less than 15 minutes every 3 or 4 weeks for patients with a creatinine clearance (CrCl) of more than 60 mL/min. Treatment is continued for 9-15 months. Oral calcium supplementation of 500 mg and a multiple vitamin containing vitamin D 400 units daily are also recommended.

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      Antifungals, Systemic

      Class Summary

      Antifungal agents such as ketoconazole produce a response similar to that of antiandrogens. These agents provide an alternative option that may produce clinical benefit if initial androgen deprivation therapy fails. These agents inhibit various cytochrome P-450 enzymes, including 11-beta-hydroxylase and 17-alpha-hydroxylase, which in turn inhibit steroid synthesis.

      Ketoconazole

      Ketoconazole is an imidazole broad-spectrum antifungal agent that acts on several of the P-450 enzymes, including the first step in cortisol synthesis, cholesterol side-chain cleavage, and conversion of 11-deoxycortisol to cortisol. It may inhibit adrenocorticotropic hormone (ACTH) secretion when used at therapeutic doses. Ketoconazole in dosages of 400 mg every 8 hours has been used in the treatment of advanced prostate cancer, although it is not FDA approved for this indication.

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      Monoclonal Antibodies, Endocrine

      Class Summary

      Monoclonal antibodies such as denosumab have been shown to decrease the incidence of skeletally related events (fractures, spinal cord compression, need for radiation therapy) in men with known bone metastases from prostate cancer.

      Denosumab (Prolia, Xgeva)

      Denosumab is a human immunoglobulin G2 (IgG2) monoclonal antibody that binds to the receptor activator of nuclear factor kappaB ligand (RANKL), which acts as the primary signal to promote bone removal. By inhibiting the development and activity of osteoclasts, denosumab decreases bone resorption and increases bone density.

      Under the brand name Prolia, denosumab is indicated for increasing bone mass in men who are at high risk for fracture because they are receiving androgen deprivation therapy for nonmetastatic prostate cancer. In these patients the dosage is 60 mg subcutaneously every 6 months.

      Under the brand name Xgeva, denosumab is indicated for the prevention of skeletally related events in men with bone metastases from prostate cancer. In these patients the dosage is 120 mg subcutaneously every 4 weeks.

      With both indications, all patients should receive calcium supplementation of 1000 mg and at least 400 units of vitamin D daily.

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      Corticosteroids

      Class Summary

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

      Prednisone (Rayos)

      Prednisone provides significant subjective palliation and reduces prostate-specific antigen (PSA) levels. Higher doses may be used in patients with spinal cord compression or cerebral edema.

      Hydrocortisone (A-Hydrocort, Cortef, Solu-Cortef)

      Hydrocortisone decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing increased capillary permeability.

      Dexamethasone (Dexamethasone Intensol)

      Dexamethasone may provide palliative benefits in patients with prostate cancer. Dexamethasone can prevent or suppress inflammation and immune responses when administered at pharmacologic doses.

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      Radiopharmaceuticals

      Class Summary

      Radiopharmaceuticals may be considered for treatment of metastatic castration-resistant prostate cancer.

      Radium-223 dichloride (Xofigo)

      Radium-223 dichloride is an alpha–particle-emitting radiopharmaceutical. This heavy metal mimics calcium and forms complexes with the bone mineral hydroxyapatite at areas of increased bone turnover, such as bone metastases. The complexes cause the double-strand DNA breaks that are lethal to the prostate cancer cell at the site of increased bone turnover induced by the cancer. It is indicated for men with castration-resistant prostate cancer with symptomatic bone metastases and no known visceral metastatic disease.

      Lutetium Lu 177 vipivotide tetraxetan (Pluvicto)

      Indicated for the treatment of men with prostate-specific membrane antigen (PSMA)-positive, metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor (AR) pathway inhibition and taxane-based chemotherapy. It is a radioligand therapeutic agent. The active moiety is the radionuclide lutetium-177, which is linked to a moiety that binds to PSMA, a transmembrane protein expressed in prostate cancer, including mCRPC. Upon binding to PSMA-expressing cells, the lutetium-177 delivers beta-minus radiation to PSMA-expressing cells, as well as to surrounding cells, inducing DNA damage that can lead to cell death.

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