abiraterone-acetate and Hypokalemia

While abiraterone acetate (AA) has demonstrated survival benefit in advanced prostate cancer (APC), meaningful cardiotoxicity is observed. It is unclear whether the magnitude differs based on disease indication and concurrent steroid administration.. We performed a systematic review and meta-analysis of phase II/III RCTs of AA in APC published as of August 11, 2020. Primary outcomes examined were all- and high-grade (grade ≥ 3) hypokalemia and fluid retention, and secondary outcomes included hypertension and cardiac events. We performed random effects meta-analysis comparing intervention (AA + steroid) and control (placebo ± steroid), stratified by treatment indication and whether patients received steroids.. Among 2,739 abstracts, we included 6 relevant studies encompassing 5901 patients. Hypokalemia and fluid retention were observed more frequently among patients receiving AA (odds ratio [OR] 3.10 [95% CI 1.69-5.67] and 1.41 [95% CI 1.19-1.66]). This was modified by whether patients in the control received steroids: trials where control patients did not demonstrated a larger association between AA and hypokalemia (OR 6.88 [95% CI 1.48-2.36] versus OR 1.86 [95% CI 4.97-9.54], P < .0001) and hypertension (OR 2.53 [95% CI 1.91-3.36] vs. OR 1.55 [95% CI 1.17-2.04], P = .1) than those where steroids were administered. We observed heterogeneity due to indication: there were greater effects on hypokalemia (P < 0001), hypertension (P = .03), and cardiac disorders (P = .01) among patients treated for mHSPC than mCRPC.. The magnitude of cardiotoxicity with AA differs based on trial design and disease indication. These data are valuable in treatment decisions and highlight utilization of appropriate data for counseling.

Topics: Abiraterone Acetate; Antineoplastic Combined Chemotherapy Protocols; Cardiotoxicity; Humans; Hypertension; Hypokalemia; Male; Mineralocorticoids; Prednisone; Prostatic Neoplasms, Castration-Resistant; Randomized Controlled Trials as Topic; Treatment Outcome

Abiraterone acetate is a CYP-17 inhibitor approved for the treatment of prostate cancer. Abiraterone acetate (AA) therapy is associated with toxicities, including hypokalemia, hypertension, liver function test abnormalities and cardiac events. These adverse events are traditionally managed with a standard dose of corticosteroids. However, preliminary data are available on the use of a lower dose of corticosteroids. The aim of this report is to perform a pooled analysis evaluating the risk ratio (RR) of AA-related adverse events of special interest associated with low or standard dose of corticosteroids. A total of 5374 cases from 4 randomized clinical trials were included. Subgroup analysis according to corticosteroids dosage revealed a higher RR of adverse events associated with a dose of 5 mg, compared to 10 mg. In particular, there was a statistically significant higher RR of hypokalemia and ALT/AST increase, and only a modest risk increase for cardiac disorders and hypertension. In conclusion, given the limitations of a literature-based study, in comparison with a meta-analysis based on individual patients' data, our study identified a relatively small increase in RR for hypertension and cardiac disorders and a bigger increase of RR for hypokalemia and ALT/AST toxicity when 5 mg, rather than 10 mg of corticosteroids were administered to manage adverse events of special interest from AA. Further studies with specified end-points are awaited to confirm these results.

Topics: Abiraterone Acetate; Adrenal Cortex Hormones; Antineoplastic Agents; Aspartate Aminotransferases; Dose-Response Relationship, Drug; Humans; Hypertension; Hypokalemia; Male; Prostatic Neoplasms; Prostatic Neoplasms, Castration-Resistant; Randomized Controlled Trials as Topic

Metastatic castration-resistant prostate cancer (mCRPC) is a disease that primarily affects older men. Abiraterone acetate (AA), a selective androgen biosynthesis inhibitor, in combination with low-dose prednisone (P) improved overall survival (OS) in a randomised trial in mCRPC progressing after docetaxel versus placebo (PL) plus P.. To examine the efficacy and safety of AA plus P versus PL plus P in subgroups of elderly (aged ≥ 75 yr) (n=331) and younger patients (<75 yr) (n=863).. We conducted a post hoc analysis of a randomised double-blind PL-controlled study in mCRPC patients progressing after docetaxel chemotherapy.. Patients were randomised 2:1 to AA (1000 mg) plus low-dose P (5mg twice daily) (n=797) or PL plus P (n=398).. Primary end point was OS. Secondary end points were time to prostate-specific antigen (PSA) progression (TTPP), radiographic progression-free survival (rPFS), and PSA response rate. Treatment differences were compared using the stratified log-rank test. The Cox proportional hazards model was used to estimate the hazard ratio (HR) and 95% confidence interval (CI). The key limitation was the post hoc analysis.. Elderly patients treated with AA plus P showed improved OS (HR: 0.64; 95% CI, 0.478-0.853; p=0.0022), TTPP (HR: 0.76; 95% CI, 0.503-1.155; p=0.1995), and rPFS (HR: 0.66; 95% CI, 0.506-0.859; p=0.0019), and higher PSA response rate with relative risk (HR: 4.15; 95% CI, 2.2-8.0]; p ≤ 0.0001) compared with patients treated with PL plus P. Grade 3/4 adverse events occurred in 62% of elderly patients and in 60% of patients aged <75 yr treated with AA plus P. Incidences of hypertension and hypokalaemia, although increased in the AA plus P arm, were similar in both age subgroups and readily managed.. AA improves OS and is well tolerated in both elderly patients and younger patients with mCRPC following docetaxel, hence providing an important treatment option for elderly patients who may not tolerate alternative therapies with greater toxicity.. ClinicalTrials.gov, identifier NCT00638690.

Topics: Abiraterone Acetate; Adult; Age Factors; Aged; Aged, 80 and over; Androstadienes; Antineoplastic Combined Chemotherapy Protocols; Disease-Free Survival; Docetaxel; Double-Blind Method; Fatigue; Humans; Hypertension; Hypokalemia; Male; Middle Aged; Prednisone; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Steroid 17-alpha-Hydroxylase; Survival Rate; Taxoids

Prostate cancer (PC) is the most common type of neoplasm in men and the fourth leading cause of mortality in Brazil. The prostate cancer refractory metastatic castration can be treated with abiraterone acetate (AA).. Its use has been associated with increased survival. However, there are also side effects associated with the use of this drug, such as severe electrolyte disturbances.. The objective is to report the clinical case of a patient with castration-resistant metastatic prostate cancer who developed ascending flaccid paralysis secondary to severe hypokalemia, probably due to hyperaldosteronism secondary to the use of Abiraterone Acetate, despite the use of Prednisone.

Topics: Abiraterone Acetate; Antineoplastic Combined Chemotherapy Protocols; Humans; Hypokalemia; Male; Paralysis; Prednisone; Prostatic Neoplasms, Castration-Resistant

We report two elderly patients receiving peritoneal dialysis with castration-resistant prostate cancer (CRPC). Herein, we show that the patients were safely treated using abiraterone acetate (750 mg/day orally once daily) and prednisolone (5 mg/day orally once daily). Although the prostate-specific antigen (PSA) level increased in both cases, there was no manifestation of disease progression (clinical and radiographic) for 22 months in case 1 and 8 months in case 2. In case 2, the only adverse event was hypokalemia, which was treated using potassium preparations.

Topics: Abiraterone Acetate; Administration, Oral; Aged, 80 and over; Antineoplastic Agents; Castration; Humans; Hypokalemia; Male; Peritoneal Dialysis; Potassium; Prednisolone; Prostatic Neoplasms, Castration-Resistant; Time Factors; Treatment Outcome

Topics: Abiraterone Acetate; Aged; Androstenes; Humans; Hypokalemia; Male; Steroid 17-alpha-Hydroxylase; Torsades de Pointes