Background & AimsVarious grades of adverse events are associated with sorafenib and have recently been considered as a surrogate of response in patients with advanced hepatocellular carcinoma. The aim of this prospective study was to measure the efficacy of a sorafenib dose reduction regimen, adjusted on patient's tolerability, and aimed at increasing the exposure to the drug. MethodsA total of 73/140 patients with advanced hepatocellular carcinoma receiving sorafenib developed relevant adverse events (grade 2) and were managed with a tolerable-adverse-event-protocol consisting of a drug stepwise dose reduction adjusted on patient's tolerability. The remaining 67 patients with toxicity grade 0-1 (minor adverse event group) were managed conventionally with just symptomatic treatment. ResultsMedian follow-up was 7 months. By adopting the tolerable-adverse-event-protocol, 48% of patients meant to transiently or definitively interrupt the drug were kept on treatment. Macrovascular invasion with/out extra-hepatic spread (HR = 1.9, 95% CI: 1.3-2.8; P = 0.001) and sorafenib exposure <2 months (HR = 4, 95% CI: 2.5-6.4; P < 0.0001) were independently related to a worse survival. Overall disease control rate, time to progression and survival were: 63.5%, 6 and 9.1 months respectively. The tolerable-adverse-event-protocol group experienced a more favourable outcome with respect to the minor adverse event group as for disease control rate (78% vs. 48%: P < 0.0001), time to progression (9.5 vs. 3 months; HR = 0.3, 95% CI: 0.2-0.5, P < 0.0001) and survival (12.5 vs. 5.7 months; HR = 0.4, 95% CI: 0.3-0.6; P < 0.0001). ConclusionsIn patients with advanced hepatocellular carcinoma, sorafenib dose adjustments based on inducing tolerability of relevant adverse events prolong drug exposure and maximize survival.
Inducing tolerability of adverse events increases sorafenib exposure and optimizes patient's outcome in advanced hepatocellular carcinoma / F.R. Ponziani, A. Germini, M. Bongini, M. Flores, C. Sposito, A. Facciorusso, A. Gasbarrini, V. Mazzaferro. - In: LIVER INTERNATIONAL. - ISSN 1478-3223. - 36:7(2016 Jul), pp. 1033-1042.
Inducing tolerability of adverse events increases sorafenib exposure and optimizes patient's outcome in advanced hepatocellular carcinoma
C. Sposito;V. Mazzaferro
2016
Abstract
Background & AimsVarious grades of adverse events are associated with sorafenib and have recently been considered as a surrogate of response in patients with advanced hepatocellular carcinoma. The aim of this prospective study was to measure the efficacy of a sorafenib dose reduction regimen, adjusted on patient's tolerability, and aimed at increasing the exposure to the drug. MethodsA total of 73/140 patients with advanced hepatocellular carcinoma receiving sorafenib developed relevant adverse events (grade 2) and were managed with a tolerable-adverse-event-protocol consisting of a drug stepwise dose reduction adjusted on patient's tolerability. The remaining 67 patients with toxicity grade 0-1 (minor adverse event group) were managed conventionally with just symptomatic treatment. ResultsMedian follow-up was 7 months. By adopting the tolerable-adverse-event-protocol, 48% of patients meant to transiently or definitively interrupt the drug were kept on treatment. Macrovascular invasion with/out extra-hepatic spread (HR = 1.9, 95% CI: 1.3-2.8; P = 0.001) and sorafenib exposure <2 months (HR = 4, 95% CI: 2.5-6.4; P < 0.0001) were independently related to a worse survival. Overall disease control rate, time to progression and survival were: 63.5%, 6 and 9.1 months respectively. The tolerable-adverse-event-protocol group experienced a more favourable outcome with respect to the minor adverse event group as for disease control rate (78% vs. 48%: P < 0.0001), time to progression (9.5 vs. 3 months; HR = 0.3, 95% CI: 0.2-0.5, P < 0.0001) and survival (12.5 vs. 5.7 months; HR = 0.4, 95% CI: 0.3-0.6; P < 0.0001). ConclusionsIn patients with advanced hepatocellular carcinoma, sorafenib dose adjustments based on inducing tolerability of relevant adverse events prolong drug exposure and maximize survival.File | Dimensione | Formato | |
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