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. 2014 Dec 9;111(12):2248-53.
doi: 10.1038/bjc.2014.531. Epub 2014 Oct 14.

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

D Lorente  1 , A Omlin  2 , R Ferraldeschi  1 , C Pezaro  1 , R Perez  1 , J Mateo  1 , A Altavilla  1 , Z Zafeirou  1 , N Tunariu  1 , C Parker  3 , D Dearnaley  3 , S Gillessen  4 , J de Bono  1 , G Attard  1
Affiliations

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

D Lorente et al. Br J Cancer. .

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.

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Figures

Figure 1
Figure 1
Waterfall graph representing PSA declines on steroid switch. (A) PSA declines at 12 weeks. (B) Maximum PSA declines. Striped bars represent patients with prior single agent dexamethasone; nonstriped bars represent patients with no prior single agent dexamethasone. PSA increases have been capped at +50%.
Figure 2
Figure 2
Top left: evolution of PSA values in a patient with a 95.6% PSA decline. Top right: evolution of PSA values (%) in patients with a ⩾ 50% PSA decline. Middle: increased bone lesion sclerosis during treatment in a patient with a 77% PSA decline. Bottom: RECIST PR in supraclavicular lymph nodes in a patient with a 30% PSA decline.
See this image and copyright information in PMC

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