Phase II Study of Abiraterone Acetate in Chemotherapy-Naive Metastatic Castration-Resistant Prostate Cancer Displaying Bone Flare Discordant with Serologic Response

Abstract

Purpose Abiraterone is an oral inhibitor of CYP17, essential for androgen biosynthesis. This multicenter study assessed its efficacy in patients with CRPC without prior exposure to chemotherapy or CYP17 targeted therapy, and assessed the frequency of interpretation of bone scans discordant with PSA and clinical response. Patients and Methods 33 patients received abiraterone acetate 1000 mg daily with prednisone 5 mg twice daily in continuous 28-day cycles. Patients were evaluated monthly for efficacy and safety. Bone scan flare was defined as the combination, after 3 months of therapy, of an interpreting radiologist's report indicating “disease progression” in the context of a ≥50% decline in PSA, with scan improvement 3 months later. Results A ≥ 50% PSA decline at week 12 was confirmed in 22/33 (67%) patients. PSA declines of ≥ 50% were seen in 26 (79%) patients. Undetectable PSA levels (≤ 0.1 ng/mL) occurred in 2 patients. Median time on therapy and time to PSA progression are 63 and 71 weeks, respectively. Twenty three patients were evaluable for bone scan flare. Progression was indicated in the radiologist's report in 12/23 (52 %), and 10/12 subsequently showed improvement. As prospectively defined, bone scan flare was observed in 10/23 (43.5%) evaluable patients or 10/33 (30%) enrolled patients. Adverse events were typically grade 1/2 and consistent with prior published abiraterone reports. Conclusion Clinical response to abiraterone acetate plus prednisone was frequent and durable in men with metastatic CRPC progressing on hormonal therapy with over half of patients on therapy > 1 year. Further investigation is needed to clarify the potential confounding effect of the frequently occurring bone scan flare phenomena on patient management and interpretation of clinical trial results.

Differential Androgen Deprivation Therapies with Anti-androgens Casodex/Bicalutamide or MDV3100/Enzalutamide versus Anti-androgen Receptor ASC-J9® Lead to Promotion versus Suppression of Prostate Cancer Metastasis

“…Earlier reports showed that the PSA level may not reflect the pathological stage progression in some PCa patients, whose PSA levels were below 0.5 ng/ml with nodal metastasis after ADT (29,30). Meanwhile, a recent clinical trial of abiraterone, a powerful drug that suppressed androgen biosynthesis, also found that although 79% of PCa patients have a decline in PSA level of 50% or more, 52% of PCa patients have either increased new bone lesions or increased intensity of existing bone lesions, which these investigators called "bone scan flare," after 4 months of treatment (31). It is interesting to note that the increase of metastasis in these PCa patients was observed at the stage when the PSA level dropped to significantly low, which might be contrary to the general concept that PSA rise during ADT is the early sign before PCa progresses to enhanced metastasis and may suggest that anti-androgen/AR signaling in PCa proliferation versus metastasis could be two different pathways.…”

Prostate Cancer, Version 3.2012 Featured Updates to the NCCN Guidelines

“…In cases in which PSA or bone scan changes may indicate flare rather than true clinical progression, therapy should be continued until clinical progression or intolerability. 28 The sequential use of other agents, such as cabazitaxel, 31 is reasonable in patients who remain candidates for further systemic therapy.…”

Avances en el tratamiento de cáncer de próstata resistente a la castración: énfasis en nuevas terapias hormonales

“…No obstante, al iniciar la terapia, en más de la mitad de los pacientes se puede observar un flare inicial en el cintigrama óseo, cuya interpretación debe ser cautelosa pues no necesariamente traduce progresión de la enfermedad 21 .…”