Tumour responses following a steroid switch from prednisone to dexamethasone in castration-resistant prostate cancer patients progressing on abiraterone.
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Date
2014-12-09Author
Lorente, D
Omlin, A
Ferraldeschi, R
Pezaro, C
Perez, R
Mateo, J
Altavilla, A
Zafeirou, Z
Tunariu, N
Parker, C
Dearnaley, D
Gillessen, S
de Bono, J
Attard, G
Type
Journal Article
Metadata
Show full item recordAbstract
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.
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Subject
Humans
Androstenes
Prednisone
Dexamethasone
Anti-Inflammatory Agents
Treatment Outcome
Retrospective Studies
Aged
Aged, 80 and over
Middle Aged
Male
Prostatic Neoplasms, Castration-Resistant
Research team
Prostate Cancer Targeted Therapy Group
Clinical Academic Radiotherapy (Dearnaley)
Treatment Resistance
Language
eng
Date accepted
2014-09-10
License start date
2014-12
Citation
British journal of cancer, 2014, 111 (12), pp. 2248 - 2253
Publisher
NATURE PUBLISHING GROUP