In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 6_suppl ( 2013-02-20), p. 156-156
Abstract:
156 Background: Platinum based therapies have demonstrated efficacy in DP mCRPC. EVE demonstrated preclinical efficacy in chemotherapy resistant prostate cancer models. Clinical synergy was noted between C and EVE, hence a phase II trial of the combination was conducted. Methods: Primary endpoint was time to progression (TTP). Progression was defined per RECIST criteria for measurable disease (MD), or skeletal event, or 〉 2 new areas of bone metastases. DP mCRPC patients with adequate renal and liver function, and performance status of 0 or 1 were eligible. Intravenous C at target AUC of 5 on day 1, and oral EVE 5mg once daily and P 5mg twice daily were administered in 21 day cycles. PSA was assessed every 21 days and radiologic response was assessed every 3 cycles. Secondary endpoints included overall survival (OS), correlation of TTP and PSA response, with markers such as phopho mTOR, pAKT, p70S6 and circulating tumor cells (CTC). Results: 26 patients (pts) enrolled, including 8 African Americans, and accrual is complete. Median age was 69 years (range 54-86). Median pretherapy PSA was 190 ng/ml (range 13 - 2174). 18 pts (69%) had bone pain. Gleason score was 〉 8 in 18 pts. 19 pts had measurable disease of which 15 had MD progression, 18 had bone scan progression, and 2 had PSA-only progression. 124 cycles have been administered; median 3 cycles (range 1 - 16). The predominant grade 3 or 4 toxicities were thrombocytopenia in 8 pts, pulmonary embolism in 2 and neutropenia in 3. No treatment related deaths occurred. Of 26 pts who are response evaluable, 4 (15%) had a 〉 30% PSA decline and 1 had a 〉 90% PSA decline. Of 19 pts with MD, 8 had stable disease and no objective responses were observed. The median TTP and OS were 2.5 months (90% CI: 1.8 - 4.3), and 12.5 months (90% CI: 6.7 - 16.1), respectively. Correlative studies including pharmacokinetic and pharmacodynamic evaluations are ongoing, and will be reported. Conclusions: The combination was tolerable but revealed modest clinical efficacy. Biomarker evaluation may help identify a subset likely to benefit from mTOR inhibition strategy in mCRPC. Clinical trial information: NCT01051570.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2013.31.6_suppl.156
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2013
detail.hit.zdb_id:
2005181-5
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