Yonsei Med J.  2013 Sep;54(5):1178-1185. 10.3349/ymj.2013.54.5.1178.

Feasibility of Sorafenib Combined with Local Radiotherapy in Advanced Hepatocellular Carcinoma

• Cha J
• Seong J
• Lee IJ
• Kim JW
• Han KH

• KMID: 1793165
• DOI: http://doi.org/10.3349/ymj.2013.54.5.1178

Abstract

PURPOSE
Sorafenib is an effective systemic agent for advanced hepatocellular carcinoma. To increase its efficacy, we evaluated the feasibility and benefit of sorafenib combined with radiotherapy.
MATERIALS AND METHODS
From July 2007 to July 2011, 31 patients were treated with a daily dose of 800 mg of sorafenib and radiotherapy. Among them, 13 patients who received radiotherapy on the bone metastasis were excluded. Thirteen patients received 30-54 Gy of radiotherapy on the primary tumor (primary group) and 5 patients received 30-58.4 Gy on the measurable metastatic lesions (measurable metastasis group). Tumor responses at 1 month after the completion of radiotherapy and overall survival were evaluated.
RESULTS
The in-field response rate was 100% in the primary group and 60% in the measurable metastasis group. A decrease of more than 80% in the tumor marker alpha-fetoprotein was observed in 7 patients in the primary group (54%). Toxicities of grades 3-4 were hand-foot syndrome in 3 (17%) patients, duodenal bleeding in 1 (6%) patient, thrombocytopenia in 3 (17%) patients and elevation of aspartate transaminase in 1 (6%) patient. The median overall survival was 7.8 months (95% confidence interval, 3.0-12.6).
CONCLUSION
The combined treatment of sorafenib and radiotherapy was feasible and induced substantial tumor responses in the target lesions. The results of this study emphasize the importance of individualized approach in the management of advanced hepatocellular carcinoma and encourage the initiation of a controlled clinical trial.

Keyword

Hepatocellular carcinoma; combined modality therapy; radiotherapy; sorafenib

MeSH Terms

Antineoplastic Agents/administration & dosage/adverse effects/*therapeutic use
Carcinoma, Hepatocellular/drug therapy/pathology/*radiotherapy
Chemotherapy, Adjuvant
Feasibility Studies
Female
Humans
Liver Neoplasms/drug therapy/pathology/*radiotherapy
Male
Niacinamide/administration & dosage/adverse effects/*analogs & derivatives/therapeutic use
Phenylurea Compounds/administration & dosage/adverse effects/*therapeutic use
Radiation Dosage
Radiotherapy/adverse effects
Antineoplastic Agents
Niacinamide
Phenylurea Compounds

Figure

• 

  Fig. 1 Illustrations of a patient in the primary group who achieved in-field CR but had out-field progression in the liver. (A) The pretreatment computed tomography (CT) scan shows two lesions. The lesion located in the segment 6 was treated with transarterial chemoembolization. (B) Axial dose distribution of 3-D conformal radiotherapy (RT). The lesion in the segment 4 was treated with RT, and (C) 1 month after completion of RT, a follow-up CT scan shows disappearance of the lesion in the segment 4. Unfortunately, the lesion in the segment 6 had progressed. CR, complete remission.

• 

  Fig. 2 Illustrations of a patient in the primary group who achieved in-field PR but showed progression of lung metastasis. (A) The pretreatment computed tomography (CT) scan shows a huge mass invading the right portal vein. Small metastatic nodules are seen in both lungs (arrows). (B) Axial dose distribution of 3-D conformal radiotherapy (RT), and (C) 1 month after completion of RT, a follow-up abdomen CT scan shows a decrease in size in the target lesion, but a chest CT scan shows new metastatic nodules in both lungs (arrows). PR, partial response.

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