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Sunitinib-induced hypertension, neutropaenia and thrombocytopaenia as predictors of good prognosis in patients with metastatic renal cell carcinoma.

Abstract：

OBJECTIVES:To evaluate the clinical significance of hypertension (HTN), neutropaenia and thrombocytopaenia as possible new biomarkers of sunitinib efficacy in non-trial patients with metastatic renal cell carcinoma (mRCC). PATIENTS AND METHODS:In all, 181 consecutive patients with mRCC were treated with sunitinib; 39 (22%) received sunitinib 50 mg/day 4 weeks on/2 weeks off, 80 (44%) received 37.5 mg/day continuously and 62 (34%) received 25 mg/day continuously as their starting dose. Treatment-induced adverse events (AEs) and their impact on outcome were analysed on multiple sunitinib doses. RESULTS:During sunitinib treatment 60 patients (33%) developed ≥grade 2 HTN, 88 (49%) ≥grade 2 neutropaenia and 135 (75%) ≥grade 1 thrombocytopaenia. These AEs were associated significantly with longer progression-free survival (PFS; 15.7 vs 6.7; 14.6 vs 6.9; 10.4 vs 4.2 months, respectively; P < 0.001) and overall survival (OS; 37.5 vs 16.2; 33.7 vs 13.2; 22.3 vs 13.2 months, respectively, P ≤ 0.008). Although only neutropaenia was associated with a significantly improved PFS and OS in all sunitinib doses, a similar trend was also seen with HTN and thrombocytopaenia in all sunitinib doses. In multivariate analysis, HTN and neutropaenia were significantly associated with PFS and OS and thrombocytopaenia was significantly associated with PFS. In a 12-week landmark analysis, HTN and thrombocytopaenia were significantly associated with PFS and OS. Patients who developed all three AEs (a favourable biomarker profile) had significantly better outcome than patients without these AEs (a poor biomarker profile); response rate 47% vs 4%, median PFS 27.1 vs 3.5 months and OS not reached vs 5.3 months (all P < 0.001). CONCLUSION:HTN, neutropaenia and thrombocytopaenia were all biomarkers of sunitinib efficacy in patients with mRCC. Our results may help to individualise sunitinib dosing during therapy based on these common sunitinib-related AEs.

journal_name

BJU Int

journal_title

BJU international

authors

Rautiola J,Donskov F,Peltola K,Joensuu H,Bono P

doi

10.1111/bju.12940

subject

Has Abstract

pub_date

2016-01-01 00:00:00

pages

110-7

issue

eissn

1464-4096

issn

1464-410X

journal_volume

117

pub_type

杂志文章

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Sunitinib-induced hypertension, neutropaenia and thrombocytopaenia as predictors of good prognosis in patients with metastatic renal cell carcinoma.