Re: Karim Fizazi, Kim N. Chi, Johann S. de Bono, et al. Low Incidence of Corticosteroid-associated Adverse Events on Long-term Exposure to Low-dose Prednisone Given with Abiraterone Acetate to Patients with Metastatic Castration-resistant Prostate Cancer. Eur Urol. In press. http://dx.doi.org/10.1016/j.eururo.2016.02.035

e17571 Background: Abiraterone acetate and prednisolone (AAP) + ADT has been approved for treatment metastatic castration-resistant prostate cancer (CRPC) in the standard dose 1,000 mg with fasting state. Data in Ramathibodi hospital showed patients who had treated with standard dose of Abiraterone acetate (AA); had PSA response 47.83%. Previous studies showed using low dose AA of 250 mg with food had the non-inferiority results in efficacy. AA was not be reimbursed in Thailand, so the ability to use a highly effective drug at a quarter of the dose, could help in patient accessibility to cancer treatments. We sought to test the hypothesis that low-dose AA with food would have the comparable activity in Thai CRPC patients in both of the pre-Docetaxel and post Docetaxel treatment groups, and exploring the quality of life (QOL) of these patients. Methods: An observational cohort enrolled newly diagnosed metastasis CRPC at Ramathibodi hospital from 1st Jan 2019 to 31st Dec 2019. Patients were assigned to AA (250mg) with actual daily life meal. We collected the data of serum PSA and the adverse events every 4 weeks for 4 months. The QOL data was collected with the EuroQoL (EQ-5D) questionnaire which were done at baseline and every 4 weeks. The primary end point was PSA response that defined as PSA decreased ≥ 50% from PSA level at baseline. The secondary endpoint were the depth of PSA change, QOL and adverse events by using Fisher's exact test and T-test. Results: 21 patients were enrolled. At 12 weeks, there were 11 patients (52.38%) achieved 50% PSA response and 6 patients (28.57%) achieved 90% PSA response. The adverse events occurred 23.8%, and mostly were mild grade. The adverse events were comparable with the historical data in standard dose of AA. Low dose AA has significantly shown the improvement in quality of life from baseline (p < 0.001), and especially the significant improvement in pre-Docetaxel subgroup. Conclusions: Low-dose AA with food has good efficacy in PSA response, adverse events and QOL. Moreover, low dose AA shows more efficacy especially in pre-Docetaxel mCRPC patients. Low dose AA may be helping in reducing cost of cancer care, enabling in delivering affordable cancer care and increasing value of treatment.

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Assessment of corticosteroid (CS)-associated adverse events (AEs) with long-term (LT) exposure to low-dose prednisone (P) given with abiraterone acetate (AA) to metastatic castration-resistant prostate cancer (mCRPC) patients (Pts).

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.7_suppl.169 ◽

2015 ◽

Vol 33 (7_suppl) ◽

pp. 169-169 ◽

Cited By ~ 1

Author(s):

Karim Fizazi ◽

Kim N. Chi ◽

Johann Sebastian De Bono ◽

Leonard G. Gomella ◽

Kurt Miller ◽

...

Keyword(s):

Low Dose ◽

Compression Fracture ◽

Abiraterone Acetate ◽

High Dose ◽

Castration Resistant Prostate Cancer ◽

Castration Resistant ◽

Common Grade ◽

Low Incidence ◽

Grade 3

169 Background: AA is the prodrug of abiraterone, which inhibits CYP17A1 and testosterone synthesis and prolongs survival of mCRPC pts. A low dose of P is given when AA is administered to mCRPC pts. LT use of moderate-/high-dose CS has an established AE profile. We investigated whether LT use of low-dose P with or without AA led to CS-associated AEs. Methods: 2,267 mCRPC pts in COU-AA-301 and COU-AA-302 received 5 mg bid P, representing 2,006 pt-yrs of P exposure. 1,333 pts received AA + P. We utilized an inclusive Standardized MedDRA Queries–oriented approach to identify 112 preferred terms for known CS-associated AEs from both databases. CS-associated AEs during 3-mo exposure intervals and across all exposure to P were assessed. Results: The overall incidence of CS-associated AEs for any P exposure was 25%, 26%, and 23% for all pts, AA + P, and P alone, respectively. The incidence of grade ≥ 3 CS-associated AEs with any P exposure was 5%, 5%, and 4% for all pts, AA + P, and P alone, respectively. The most common grade ≥ 3 CS-associated AEs occurring in ≥ 0.1% of all pts were hyperglycemia (2%), cataract (0.4%), diabetes mellitus (0.4%), gastrointestinal hemorrhage (0.3%), adrenal insufficiency (0.1%), hip fracture (0.1%), melena (0.1%), and spinal osteoporotic compression fracture (0.1%). The overall incidence of weight increase (grade 1/2 only) was 4%, 4%, and 5% for all pts, AA + P, and P alone, respectively. Most were grade 1 (3.4%).When assessed by duration of exposure (3-mo intervals up to ≥30 mo), grade ≥ 3 CS-associated AEs fluctuated between 1% and 2%, but no discernable trend was observed. The observed change in weight from baseline showed no apparent increase over time. Conclusions: With over 2,000 pt-yrs of exposure, low-dose P given with or without AA is associated with an overall low incidence of CS-associated AEs. The frequencies of CS-associated AEs were low with increased duration of exposure to P. Clinical trial information: NCT00638690 , NCT00887198 .

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