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Apalutamide: Antiandrogen for Castration Resistant Prostate Cancer
Indications for Apalutamide
Castration-resistant non-metastatic prostate cancer (M0 CRPC):
Apalutamide is a treatment option for patients with rising PSA levels under androgen deprivation therapy without metastasis in imaging studies (scintigraphy, CT). The approval is limited to patients at high risk: PSA doubling time under 10 months. In the pivotal study (SPARTAN), treatment with apalutamide combined with classic antiandrogen therapy improved metastasis-free survival (41 months vs. 16 months with placebo and hormone therapy). Overall survival was improved with apalutamide, but this was statistically only a trend (Smith et al, NEJM 2018).
Castration-resistant metastatic prostate cancer (M1 CRPC):
Apalutamid is not approved for treatment of M1 CRPC.
Castration-sensitive metastatic prostate carcinoma (M1 CSPC):
Apalutamid is not approved for treatment of M1 CSPC.
Mechanism of Action of Apalutamide
Apalutamide inhibits the signal transduction of the androgen receptor: p>
- Competitive inhibition of the androgen binding to the androgen receptor
- Prevents translocation of activated receptors to the cell nucleus
- Inhibits the binding of the activated androgen receptor to the DNA
Pharmacokinetics of Apalutamide
100% bioavailability independent from meals, 96% plasma protein binding, hepatic metabolism of apalutamide mainly via CYP2C8 and CYP3A4, half-life 3 days, renal (65%) and fecal excretion of the inactive metabolites.
Side Effects of Apalutamide
The most common side effects are fatigue (30%) and rash (24% all severity grades and 5% grade 3 or 4). In more than 80% of patients the exanthem improved by dose reduction, systemic corticosteroids or pausing of the medication (see dosage). Further side effects are weight loss (16%), arthralgia (16%), increased risk of falling with fractures (12%), hypothyroidism (8%), epilepsy (<1%).
Interactions with Apalutamide
Apalutamide is a potent enzyme inducer, so caution is recommended with many drug groups such as antiepileptics or oral anticoagulation.
Contraindications for Apalutamide
- Allergy and intolerance
- Women and children
- Severe hepatic impairment
Dosage of Apalutamide
240 mg apalutamide (four 60 mg capsules) p.o. once a day. The addition of prednisolone is not necessary. For rash ≥grade 3, the medication should be paused to allow recovery. If necessary add local or systemic glucocorticoids. If the rash recurs at re-dosing of 240 mg, a dose reduction to 120–180 mg should be attempted. Discontinue treatment in patients with progressive disease or persistent intolerance to enzalutamide.
Index: 1–9 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
- Smith, M. R.; Saad, F.; Chowdhury, S.; Oudard, S.; Hadaschik, B. A.; Graff, J. N.; Olmos, D.; Mainwaring, P. N.; Lee, J. Y.; Uemura, H.; Lopez-Gitlitz, A.; Trudel, G. C.; Espina, B. M.; Shu, Y.; Park, Y. C.; Rackoff, W. R.; Yu, M. K.; Small, E. J. & Investigators, S.
Treatment and Metastasis-free Survival in Prostate Cancer.
The New England journal of medicine, 2018
Deutsche Version: Apalutamid