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Abiraterone: Androgen Synthesis Inhibitor for Metastatic Prostate Cancer
Indications for Abiraterone
Castration-Sensitive Metastatic Prostate Carcinoma (M1 CSPC)
Abiraterone is an treatment option for men with high tumor burden of castration-sensitive metastatic prostate cancer. At least 4 bone metastases or the presence of visceral metastases were defined as high tumor burden (Sweeney et al., 2015). The approval of abiraterone was expanded in 2017 based on the results of the STAMPEDE trial (James et al., 2017) and LATITUDE trial (Fizazi et al., 2017). The combination ofstandard androgen deprivation therapy with abiraterone 1000 mg/d and prednisolone 5 mg/d resulted in improved survival (83% vs. 76%), prolonged progression-free survival and prolonged time to chemotherapy.
Castration-Resistant Non-Metastatic Prostate Cancer (M0 CRPC)
Abiraterone is not approved for the treatment of increasing PSA levels under classical androgen deprivation therapy and without the detection of metastases in imaging (scintigraphy, CT).
Castration-Resistant Metastatic Prostate Cancer (M1 CRPC)
Abiraterone is an option to treat men with castration-resistant metastatic prostate cancer before or after chemotherapy. Abiraterone increases survival in patients with CRPC after docetaxel chemotherapy (14.8 vs. 10.9 months) compared to placebo (Bono et al., 2011). Abiraterone also improves prognosis before docetaxel chemotherapy treatment in patients with M1 CRPC: prolonged progression-free survival (16.5 vs. 8.3 months) and overall survival (Ryan et al., 2013).
Mechanism of Action of Abiraterone
Abiraterone is a CYP-17 inhibitor and thus an inhibitor of the testosterone biosynthesis.
Pharmacokinetics of Abiraterone
Taking Abiraterone with meals leads to a massive increase in absorption with up to 17-fold increase in peak concentration, therefore intake with meals must be avoided (see dosage). High distribution volume and high plasma protein binding. Elimination half life 15 h, hepatic metabolism and biliary elimination.
Side Effects of Abiraterone
- Hepatotoxicity with increased GOT and GPT
- Fluid retention with peripheral edema as a result of mineralcorticoid excess with hypertension and hypokalemia
- Abiraterone leads to a decrease in bone density
- Urinary tract infection
Interactions with Abiraterone
Abiraterone activates the enzyme CYP2D6, therefore dose reduction or caution with metoprolol, propranolol, desimpramine, haloperidol, risperidone, propafenone, flecanide, codeine, oxycodone and tramadol.
Contraindications for Abiraterone
- Allergy and intolerance
- Women and children
- Moderate or severe hepatic impairment (Child-Pugh B and C)
- Hepatotoxicity during treatment (ALT and/or AST greater than 5× upper limit of normal value or total bilirubin greater than 3× ULN
Dosage of Abiraterone
The dosage of abiraterone is 1000 mg 1-0-0 p.o. Abiraterone must be taken on an empty stomach, no food should be consumed for at least two hours before the dose and for at least one hour after the dose. Abiraterone is prescribed together with Prednisolone 10 mg 1-0-0.
Brand Name of Abiraterone:
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- de Bono, J. S.; Logothetis, C. J.; Molina, A.; Fizazi, K.; North, S.; Chu, L.; Chi, K. N.; Jones, R. J.; Goodman, O. B.; Saad, F.; Staffurth, J. N.; Mainwaring, P.; Harland, S.; Flaig, T. W.; Hutson, T. E.; Cheng, T.; Patterson, H.; Hainsworth, J. D.; Ryan, C. J.; Sternberg, C. N.; Ellard, S. L.; Fléchon, A.; Saleh, M.; Scholz, M.; Efstathiou, E.; Zivi, A.; Bianchini, D.; Loriot, Y.; Chieffo, N.; Kheoh, T.; Haqq, C. M.; Scher, H. I. & Investigators, C. O. U. A.
and increased survival in metastatic prostate cancer.
N Engl J Med, 2011, 364, 1995-2005
- Ryan, C. J.; Smith, M. R.; de Bono, J. S.; Molina, A.; Logothetis, C. J.; de Souza, P.; Fizazi, K.; Mainwaring, P.; Piulats, J. M.; Ng, S.; Carles, J.; Mulders, P. F. A.; Basch, E.; Small, E. J.; Saad, F.; Schrijvers, D.; Poppel, H. V.; Mukherjee, S. D.; Suttmann, H.; Gerritsen, W. R.; Flaig, T. W.; George, D. J.; Yu, E. Y.; Efstathiou, E.; Pantuck, A.; Winquist, E.; Higano, C. S.; Taplin, M.; Park, Y.; Kheoh, T.; Griffin, T.; Scher, H. I.; Rathkopf, D. E. & Investigators, C. O. U. A.
in metastatic prostate cancer without previous chemotherapy.
N Engl J Med, 2013, 368, 138-148.
Deutsche Version: Abirateron