Dataset Information

Tumour responses following a steroid switch from prednisone to dexamethasone in castration-resistant prostate cancer patients progressing on abiraterone.

ABSTRACT: BACKGROUND:Abiraterone is a CYP17A1 inhibitor that improves survival in castration-resistant prostate cancer (CRPC). Abiraterone is licensed in combination with prednisone 5?mg twice daily to prevent a syndrome of secondary mineralocorticoid excess. We hypothesised that a 'steroid switch' from prednisone to dexamethasone would induce secondary responses in patients progressing on abiraterone and prednisone 5?mg b.i.d. METHODS:We performed a 'steroid switch' in patients with CRPC at PSA progression on abiraterone and prednisolone. Patients were monitored for secondary declines in PSA, radiological tumour regression and toxicity. RESULTS:A retrospective analysis of 30 CRPC patients who underwent a steroid switch from prednisolone to dexamethasone while on abiraterone was performed. A total of six patients (20%) had a ?50% PSA decline that was confirmed by a second PSA level at least 3 weeks later. In all, 11 patients (39.2%) had a confirmed ?30% PSA decline. Median time to PSA progression on abiraterone and dexamethasone was 11.7 weeks (95% CI: 8.6-14.8 weeks) in the whole cohort and 27.6 weeks (95% CI: 14.5-40.7 weeks) in patients who achieved a confirmed 50% PSA decline. Nine patients had RECIST evaluable disease: two of these patients had RECIST partial response, six patients had stable disease and one patient had progressive disease at the first imaging assessment. Treatment was well tolerated, with no grade 3 and grade 4 adverse events. One patient had to be reverted to prednisolone because of grade 2 hypotension. CONCLUSIONS:Durable PSA responses occur in up to 40% of patients following a 'steroid switch' for PSA progression on abiraterone and prednisone. Studies are ongoing to elucidate the mechanisms underlying this response.

SUBMITTER: Lorente D

PROVIDER: S-EPMC4264443 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Tumour responses following a steroid switch from prednisone to dexamethasone in castration-resistant prostate cancer patients progressing on abiraterone.

Lorente D D Omlin A A Ferraldeschi R R Pezaro C C Perez R R Mateo J J Altavilla A A Zafeirou Z Z Tunariu N N Parker C C Dearnaley D D Gillessen S S de Bono J J Attard G G

British journal of cancer 20141014 12

<h4>Background</h4>Abiraterone is a CYP17A1 inhibitor that improves survival in castration-resistant prostate cancer (CRPC). Abiraterone is licensed in combination with prednisone 5 mg twice daily to prevent a syndrome of secondary mineralocorticoid excess. We hypothesised that a 'steroid switch' from prednisone to dexamethasone would induce secondary responses in patients progressing on abiraterone and prednisone 5 mg b.i.d.<h4>Methods</h4>We performed a 'steroid switch' in patients with CRPC a ...[more]

PMID: 25314055

Similar Datasets

Project description:BackgroundThe optimal sequencing of the multiple active agents now available for metastatic castration-resistant prostate cancer (mCRPC) is unclear. Prior reports have suggested diminished responses to sequential lines of androgen receptor (AR)-targeted therapies, but it is unknown whether subsequent taxane-based chemotherapy may be more effective than sequential AR-targeting treatment. We sought to evaluate the clinical activity of enzalutamide versus docetaxel in men with mCRPC who progressed on abiraterone.MethodsWe performed a single-institution retrospective analysis of consecutive mCRPC patients who had progressed on abiraterone therapy and subsequently received either enzalutamide (n=30) or docetaxel (n=31). We evaluated clinical outcomes including prostate-specific antigen decline of >30% (PSA30) or >50% (PSA50), PSA-progression-free survival (PSA-PFS), and clinical/radiographic PFS. We performed multivariable modeling to control for baseline and on-treatment differences between groups.ResultsCompared to subjects who received enzalutamide post-abiraterone, subjects who received docetaxel post-abiraterone had more bone metastases, more visceral metastases, higher baseline PSA, and had more frequent PSA tests while on-treatment. There were no significant differences in PSA30 (41% for enzalutamide vs. 53% for docetaxel) or PSA50 (34% vs. 40%) response rates between the two groups; there remained no difference after stratifying by presence/absence of prior response to abiraterone. Median PSA-PFS was 4.1 versus 4.1 months for the enzalutamide and docetaxel cohorts, respectively (HR 1.35, 95% CI, 0.53-3.66, P=0.502). Median PFS was 4.7 versus 4.4 months, respectively (HR 1.44, 95% CI, 0.77-2.71, P=0.257). PSA-PFS and PFS did not differ after stratifying by prior response to abiraterone. In multivariable analyses, there were no significant differences in PSA-PFS or PFS between the two groups.ConclusionsTreatment with either enzalutamide or docetaxel produced modest PSA responses and PFS intervals in this abiraterone-pretreated mCRPC population. In this retrospective study with small sample size, no significant differences in outcomes were observed between groups. Therefore, either enzalutamide or docetaxel may be a reasonable option in men who have progressed on abiraterone.

Dataset Information

Tumour responses following a steroid switch from prednisone to dexamethasone in castration-resistant prostate cancer patients progressing on abiraterone.

Publications

Tumour responses following a steroid switch from prednisone to dexamethasone in castration-resistant prostate cancer patients progressing on abiraterone.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets