Efficacy and Safety of Liver-Directed Concurrent Chemoradiotherapy and Sequential Sorafenib for Advanced Hepatocellular Carcinoma: A Prospective Phase 2 Trial

Beom Kyung Kim, Do Young Kim, Hwa Kyung Byun, Hye Jin Choi, Seung Hoon Beom, Hye Won Lee, Seung Up Kim, Jun Yong Park, Sang Hoon Ahn, Jinsil Seong, Kwang Hyub Han

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Purpose: Although sorafenib as a standard of care for advanced hepatocellular carcinoma (HCC) prolongs overall survival (OS), its efficacy is limited owing to its unsatisfactory objective response and marginal survival benefit. To counter these limitations, we designed a single-arm, phase II trial with liver-directed concurrent chemoradiotherapy (LD-CCRT) and sequential sorafenib treatment in patients with advanced HCC. Methods and Materials: We enrolled advanced HCC patients diagnosed between 2014 and 2017 who were ineligible for curative treatment. During the first and last 5 days of 5-week radiation therapy, concurrent hepatic arterial infusion with 5-fluorouracil (500 mg/d) and leucovorin (50 mg/d) through an implanted port was administered 4 weeks after initiation of LD-CCRT and sequential sorafenib treatment (400 mg, twice daily). The primary endpoint was OS. This trial has been registered at clinicaltrials.gov. Results: Among the enrolled patients (n = 47), objective response rates 4 weeks after LD-CCRT and during/up to sorafenib maintenance were 44.7% and 53.2%, respectively. Overall, 9 patients (19.1%) underwent curative resection or transplantation after down staging. The median radiation dose was 60 Gy. The median OS was 24.6 months for the entire cohort and 13.0 months for the subgroup with tumor invasion into the main portal trunk or its first branch, whereas the median progression-free survival for the cohort and subgroup was 6.8 and 5.6 months, respectively. The most frequent treatment-related adverse events were diarrhea (36.2%) and hand-foot skin reaction (34%), which were manageable with conservative treatment. Conclusions: LD-CCRT and sequential sorafenib treatment provided favorable OS and progression-free survival with good tolerability. Tumor reduction using an initial LD-CCRT enabled down staging, subsequent curative treatment, and long-term survival in about 20% of the patients with advanced HCC. However, further randomized trials are required to confirm these results.

Original languageEnglish
Pages (from-to)106-115
Number of pages10
JournalInternational Journal of Radiation Oncology Biology Physics
Issue number1
Publication statusPublished - 2020 May 1

Bibliographical note

Funding Information:
The English in this manuscript was checked not only by professional editors at Editage, a division of Cactus Communication, but also by a professional English editor from the Research Department of Yonsei University College of Medicine, Seoul, Republic of Korea. This study was supported by the research supporting program of the Korean Association for the Study of the Liver and The Korean Liver Foundation (KASLKLF2015-05). The funder had no role in the study design, data collection, analysis, interpretation, or writing of the report.

All Science Journal Classification (ASJC) codes

  • Radiation
  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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