Dr. med. Dirk Manski



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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:

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

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.







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References

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.
Apalutamide Treatment and Metastasis-free Survival in Prostate Cancer.
The New England journal of medicine, 2018


  Deutsche Version: Apalutamid