Phase II Study of Sorafenib Combined with Concurrent Hepatic Arterial Infusion of Oxaliplatin, 5-Fluorouracil and Leucovorin for Unresectable Hepatocellular Carcinoma with Major Portal Vein Thrombosis
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Sorafenib is recommended for the first-line treatment of advanced hepatocellular carcinoma (HCC). However, the median progression-free survival (PFS) of patients with HCC and major portal vein tumor thrombosis treated with sorafenib monotherapy is no more than 3 months. A prospective single-arm phase II study was conducted to determine whether adding hepatic arterial infusion chemotherapy of oxaliplatin, 5-fluorouracil and leucovorin to sorafenib could improve on these results.
Thirty five patients were treated with sorafenib 400 mg orally twice a day, oxaliplatin 85 mg/m2 HAI on day 1, leucovorin 400 mg/m2 HAI on days 1, and 5-fluorouracil 2800 mg/m2 on days 1 and 2, repeated every 21 days. The primary end point was the 3-month PFS rate.
The 3-, 6-, and 12-month PFS rates were 82.9, 51.4, and 22.9%, respectively. The median PFS and overall survival was 6.7 and 13.2 months, respectively. The objective response rate was 40%, and the disease control rate was 77.1% by RECIST criteria. Five (14.3%) patients achieved conversion to complete resection after the study treatment, and one of them experienced a pathological complete response. Treatment-related deaths did not occur. Grade 3–4 toxicities consisted of increases in aspartate aminotransferase (31.4%), hand-foot syndrome (17.1%), thrombocytopenia (14.3%), and neutropenia (8.6%).
The combination treatment met the pre-specified end point of a 3-month progression free survival rate exceeding 65% and was clinical tolerable. The merits of this approach need to be established with a phase III trial.
Clinical trial number http://ClinicalTrials.gov (No. NCT02981498).
KeywordsHepatocellular carcinoma Tumor thrombosis Hepatic arterial infusion chemotherapy (HAIC) Sorafenib Oxaliplatin Fluorouracil
This work was supported by National Key R&D Program of China (2017YFA0505803), and the National Natural Science Foundation of China (Nos. 81625017, 81572385), and the Fundamental Research Funds for the Central Universities of China (No. 16ykjc36).
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Conflict of interest
The authors declare that they have no conflict of interest. The manuscript has not been submitted to more than one journal for simultaneous consideration. The manuscript has not been published previously (partly or in full). A single study is not split up into several parts to increase the quantity of submissions and submitted to various journals or to one journal over time. No data have been fabricated or manipulated (including images) to support your conclusions. No data, text, or theories by others are presented as if they were the author’s own (“plagiarism”). Consent to submit has been received explicitly from all co-authors, as well as from the responsible authorities—tacitly or explicitly—at the institute/organization where the work has been carried out, before the work is submitted.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. All patients provided written informed consent. The study was approved by the institutional review board.