Safety and efficacy of cytotoxic chemotherapy in hepatocellular carcinoma after first-line treatment with sorafenib

Leonardo Gomes Da Fonseca,Flair Jose Carrilho,Maria Ignez Freitas Melro Braghiroli,Jorge Sabbaga,Paulo Marcelo Hoff,Aline Lopes Chagas,Guilherme Nader Marta

doi:10.1186/s12885-018-5173-0

Leonardo Gomes Da Fonseca, Flair Jose Carrilho + Show 5 more

Open Access

https://doi.org/10.1186/s12885-018-5173-0

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Abstract

BackgroundBefore the targeted therapies era, cytotoxic chemotherapy (CCT) was an option for advanced hepatocellular carcinoma (HCC), even with the lack of supporting evidence. Since the last decade, sorafenib has been established as the first-line therapy. Although new agents are being incorporated, CCT is still considered in regions where new drugs are not available or for patients who progressed through the approved therapies and remain in good clinical condition. We aimed to describe our experience regarding the use of CCT as second-line treatment after sorafenib.MethodsA database of 273 patients was evaluated. Patients that received CCT after sorafenib progression were selected for the analysis. Descriptive statistics was used for categorical and continue variables. Median survival was estimated with Kaplan-Meier curves. Variables were found to be significant if the two-sided p value was ≤ 0.05 on multivariate testing using the Cox regression model.ResultsForty-five patients received CCT; 33 (73.3%) had Child-Pugh classification A, and 34 (75.6%) had stage C according to the Barcelona Clinic Liver Cancer (BCLC) staging system. The most used regimen was doxorubicin in 25 patients (55.6%). Median overall survival (OS) was 8.05 months (95% confidence interval [CI] 2.73 – 9.88 months). The 6-month and 1-year survival probability was 52.4% and 27.36%, respectively. Eastern Cooperative Oncology Group performance status (ECOG PS) 0–1 and disease control with sorafenib was independently associated with better OS in patients treated with CCT. Any-grade toxicities were observed in 82.2% and grade 3–4 in 44.4% of the patients.ConclusionIn accordance with previous studies, CCT had a notable rate of adverse events. The poor prognosis of this cohort suggests that CCT may not alter the natural history of HCC after sorafenib progression.

Highlights

Before the targeted therapies era, cytotoxic chemotherapy (CCT) was an option for advanced hepatocellular carcinoma (HCC), even with the lack of supporting evidence
Patients and methods A database of 273 consecutive HCC patients treated with sorafenib at Instituto do Cancer do Estado de São Paulo, Universidade de São Paulo, Brazil, from July 2009 to January 2017 was retrospectively evaluated after approval by the local ethics committee
Baseline characteristics Between July 2009 and January 2017, a total of 273 patients who received sorafenib as first-line therapy for HCC were enrolled in this analysis

Summary

Introduction

Before the targeted therapies era, cytotoxic chemotherapy (CCT) was an option for advanced hepatocellular carcinoma (HCC), even with the lack of supporting evidence. Hepatocellular carcinoma (HCC) is the sixth most common neoplasm and the third leading cause of cancer-related death [1]. This high rate of mortality is mainly associated with the coexistence of underlying cirrhosis and the considerable proportion of patients diagnosed in advanced stage [2]. A multi-kinase inhibitor, showed consistent overall survival (OS) improvement in two phase III placebo-controlled trials and is considered the standard first-line therapy [3, 4]. Cabozantinib was shown to be superior to placebo in terms of OS after at least one previous systemic therapy, Fonseca et al BMC Cancer (2018) 18:1250 including sorafenib, and can be an alternative in the second-line [7]

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