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Efficacy and Safety of Liver-Directed Concurrent Chemoradiotherapy and Sequential Sorafenib for Advanced Hepatocellular Carcinoma: A Prospective Phase 2 Trial
- Source :
- Ann Transl Med
- Publication Year :
- 2020
- Publisher :
- Elsevier BV, 2020.
-
Abstract
- 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.
- Subjects :
- Male
Sorafenib
Cancer Research
medicine.medical_specialty
Carcinoma, Hepatocellular
Time Factors
Gastroenterology
030218 nuclear medicine & medical imaging
law.invention
03 medical and health sciences
0302 clinical medicine
Hepatic arterial infusion
Randomized controlled trial
law
Internal medicine
medicine
Clinical endpoint
Humans
Radiology, Nuclear Medicine and imaging
Prospective Studies
Prospective cohort study
Aged
Radiation
business.industry
Liver Neoplasms
Chemoradiotherapy
Middle Aged
medicine.disease
Survival Analysis
Transplantation
Editorial Commentary
Treatment Outcome
Oncology
Tolerability
030220 oncology & carcinogenesis
Hepatocellular carcinoma
Female
Safety
business
medicine.drug
Subjects
Details
- ISSN :
- 03603016
- Volume :
- 107
- Database :
- OpenAIRE
- Journal :
- International Journal of Radiation Oncology*Biology*Physics
- Accession number :
- edsair.doi.dedup.....87c9746343290d03df9ed882c4e0686f