Safety and effectiveness of sorafenib in patients with hepatocellular carcinoma in clinical practice.
ABSTRACT Sorafenib is currently the only approved systemic treatment for hepatocellular carcinoma.
to evaluate safety and effectiveness of sorafenib in the field of practice.
We report a single-centre experience on 116 advanced hepatocellular carcinoma patients treated with sorafenib between February 2008 and March 2011. Every 4 weeks, adverse events were graded using Common Toxicity Criteria version 3.0, and every 3 months tumour response was assessed according to modified Response Evaluation Criteria in Solid Tumours for hepatocellular carcinoma.
Cirrhosis was present in 95.7% of patients (83.6% Child-Pugh A class), hepatitis C was the main etiological factor. Median therapy duration was 3 months and median daily dose was 642 mg. Median time-to-radiological progression in the per-protocol population was 12 months and median overall survival in the intention-to-treat population was 13 months. 91.4% of patients experienced mild adverse events (grade 1 or 2), the most frequent were gastrointestinal and dermatological. Jaundice and bleeding were the main causes of definitive drug discontinuation. 3-month overall disease control rate was 70.6%: stable disease in 37.2%, partial response in 30.8%, and complete response in 2.6% patients. The 3-month radiological response correlated with overall survival.
In daily clinical practice, sorafenib confirmed its safety and efficacy in hepatocellular carcinoma patients.
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ABSTRACT: Hypertension is one of the major side effects of sorafenib, and reported incidences vary substantially among clinical trials. A systematic review was conducted using Medline, PubMed, Embase, and the Cochrane Library for all longitudinal studies to investigate the incidence and risk of hypertension events in cancer patients treated with sorafenib. A total of 14 randomized controlled trials and 39 prospective single-arm trials involving 13,555 patients were selected for the meta-analysis. The relative risk of all-grade and high-grade hypertension associated with sorafenib were 3.07 (95% confidence interval [CI], 2.05-4.60; P<.01) and 3.31 (95% CI, 2.21-4.95; P<.01), respectively. The overall incidence of sorafenib-induced all-grade and high-grade hypertension were 19.1% (95% CI, 15.8%-22.4%) and 4.3% (95% CI, 3.0%-5.5%), respectively. A significantly higher incidence of hypertension was noted in patients with renal cell carcinoma (RCC) compared with those with non-RCC malignancies (all-grade: 24.9% [95% CI, 19.7%-30.1%] vs 15.7% [95% CI, 12.1%-19.3%]; P<.05; high-grade:8.6% [95% CI, 6.0%-11.2%] vs 1.8% [95% CI, 0.9%-2.6%]; P<.05). The trials with median progression-free survival (PFS) longer than 5.3 months (mean PFS) demonstrated a significantly higher incidence of high-grade hypertension than trials with shorter PFS (6.3% [95% CI, 4.1%-8.5%] vs 2.6% [95% CI, 1.4%-3.8%]; P<.05). Findings of the meta-analysis indicated a significantly high risk of sorafenib-induced hypertension. Patients with RCC have a significantly higher incidence of hypertension and the occurrence of hypertension may be associated with improved prognosis.Journal of Clinical Hypertension 03/2014; · 2.36 Impact Factor
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ABSTRACT: Backgroundsorafenib and transarterial 90Y-radioembolization (TARE) are possible treatments for Barcelona Clinic Liver Cancer (BCLC) intermediate-advanced stage hepatocellular carcinoma (HCC). No study directly comparing sorafenib and TARE is currently available. Aim: This single-center retrospective study compares the outcomes achieved with sorafenib and TARE in HCC patients potentially amenable to either therapy.Methods Seventy-four sorafenib (71±10 years, male 87%, BCLC B/C 53%/47%) and 63 TARE HCC patients (66±9 years, male 79%, BCLC B/C 41%/59%) were included based on the following criteria: Child-Pugh class A/B, performance status ≤1, HCC unfit for other effective therapies, no metastases, no previous systemic chemotherapy.Resultsmedian overall survivals of the two groups were comparable, being 14.4 months (95% Confidence Interval: 4.3-24.5) in sorafenib and 13.2 months (95% Confidence Interval: 6.1-20.2) in TARE patients, with 1-, 2- and 3-year survival rates of 52.1%, 29.3% and 14.7% versus 51.8%, 27.8% and 21.6%, respectively. Two TARE patients underwent liver transplantation after successful downstaging. To minimize the impact of confounding factors on survival analysis, propensity model matched 32 patients of each group for median age, tumor gross pathology and the independent prognostic factors (portal vein thrombosis, performance status, Model for End Liver Disease). Even after matching, the median survival did not differ between sorafenib (13.1 months; 95% Confidence Interval: 1.2-25.9) and TARE patients (11.2 months; 95% Confidence Interval: 6.7-15.7), with comparable 1-, 2- and 3-year survival rates.Conclusionsin cirrhotic patients with intermediate-advanced or not-otherwise-treatable HCC, sorafenib and TARE provide similar survivals. Down-staging allowing liver transplantation only occurred after TARE.This article is protected by copyright. All rights reserved.Liver international: official journal of the International Association for the Study of the Liver 04/2014; · 3.87 Impact Factor
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ABSTRACT: There are no clinical data/markers to predict improved survival in patients with hepatocellular carcinoma treated with sorafenib. Majority of sorafenib adverse events appear within the first 60 days of treatment and studies correlating them with outcome are needed. We prospectively studied 147 hepatocellular carcinoma patients (97% cirrhotic, 82% Child-Pugh A, BCLC-B 77, BCLC-C 69) treated with sorafenib. Follow-up included monthly clinical and laboratory monitoring and tumor staging at week 4 and every 8 weeks. After a median follow up of 11.6 months (treatment duration 6.7 months), time to progression and overall survival were 5.1 and 12.7 months. All but one patient presented at least one adverse event (median time to appearance 56 days). Time dependent covariate analysis (HR [CI95%]) identified baseline performance status (2.86 [1.75 to 4.55], p<0.001), BCLC (1.69 [1.18 to 2.50], p=0.005) and dermatologic adverse event requiring dose adjustment within the first 60 days (0.58 [0.36 to 0.92], p=0.022) as independent predictors of better outcome. Other early adverse events did not have an impact in outcome. The predictive value of dermatologic adverse events for survival was confirmed by the landmark analysis (p= 0. 0270). Development of dermatologic adverse events within 60 days of sorafenib initiation is associated with better survival. Therefore, this should not to be taken as a negative event and discourage treatment maintenance. Likewise, second line clinical trials should be designed and/or evaluated considering this information to avoid significant bias.Journal of Hepatology 04/2014; · 9.86 Impact Factor