International Journal of
Radiation Oncology biology
physics
www.redjournal.org
Clinical Investigation: Gastrointestinal Cancer
Phase 2 Study of Combined Sorafenib and Radiation Therapy in Patients With Advanced Hepatocellular Carcinoma Shang-Wen Chen, MD,z,x,k Li-Ching Lin, MD,y,x Yu-Cheng Kuo, MD, PhD,z,{ Ji-An Liang, MD,z,k Chia-Chun Kuo, MD,* and Jeng-Fong Chiou, MD, PhD*,x *Department of Radiation Oncology, Taipei Medical University Hospital, Taipei, Taiwan; yDepartment of Radiation Oncology, Chi-Mei Hospital, Tainan, Taiwan; zDepartment of Radiation Oncology, China Medical University Hospital, Taichung, Taiwan; xSchool of Medicine, Taipei Medical University, Taipei, Taiwan; kSchool of Medicine, China Medical University, Taichung, Taiwan; and {Department of Biomedical Imaging and Radiological Science, China Medical University, Taichung, Taiwan Received Oct 23, 2013, and in revised form Jan 4, 2014. Accepted for publication Jan 13, 2014.
Summary The tolerance and toxicities of radiation therapy with concurrent and sequential sorafenib are acceptable in patients with hepatoma. Hepatic toxicities are a major determinant of the combined treatment. Following radiation therapy with concurrent sorafenib therapy, the complete and partial response rates were 55% with a 2-year infield progression-free survival of 39%. The Cancer of the Liver Italian Program score of 2 was associated with an inferior outcome in overall survival.
Purpose: This phase 2 study evaluated the efficacy of radiation therapy (RT) with concurrent and sequential sorafenib therapy in patients with unresectable hepatocellular carcinoma (HCC). Methods and Materials: Forty patients with unresectable HCC unfit for transarterial chemoembolization were treated with RT with concurrent and sequential sorafenib. Sorafenib was administered from the commencement of RT at a dose of 400 mg twice daily and continued to clinical or radiologic progression, unacceptable adverse events, or death. All patients had underlying Child-Pugh A cirrhosis. The maximal tumor diameter ranged from 3.0 cm to 15.5 cm. Coexisting portal vein thrombosis was found in 24 patients and was irradiated simultaneously. The cumulative RT dose ranged from 40 Gy to 60 Gy (median, 50 Gy). Image studies were done 1 month after RT and then every 3 months thereafter. Results: Thirty-three (83%) completed the allocated RT. During RT, the incidence of hand-foot skin reactions grade 2 and diarrhea were 37.5% and 25%, respectively, and 35% of patients had hepatic toxicities grade 2. Twenty-two (55.0%) patients achieved complete or partial remission at the initial assessment, and 18 (45%) had stable or progressive disease. The 2-year overall survival and infield progressionfree survival (IFPS) were 32% and 39%, respectively. A Cancer of the Liver Italian Program (CLIP) score 2 was associated with an inferior outcome in overall survival.
Reprint requests to: Jeng-Fong Chiou, MD, PhD, Department of Radiation Oncology, Taipei Medical University Hospital, Taipei; Tel: +886-227372181 ex:2130. E-mail: [email protected] This study was supported by funding from Bayer Healthcare. Conflict of interest: none. Supplementary material for this article can be found at www.redjournal.org. Int J Radiation Oncol Biol Phys, Vol. 88, No. 5, pp. 1041e1047, 2014 0360-3016/$ - see front matter Ó 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.ijrobp.2014.01.017
AcknowledgmentsdThe authors thank the following coinvestigators for their help in conducting the trial and patient care: Belle Kang and ChiaHsin Pan, Taipei Medical University Hospital, Taiwan; Ya-Ju Hsiao, China Medical University Hospital, Taiwan; Ru-Chi Lee, Chi-Mei Hospital, Taiwan. This research was supported by Bayer Healthcare Pharmaceuticals.
International Journal of Radiation Oncology Biology Physics
1042 Chen et al.
Six patients (15%) developed treatment-related hepatic toxicity grade 3 during the sequential phase, and 3 of them were fatal. Conclusions: When RT and sorafenib therapy were combined in patients with unresectable HCC, the initial complete or partial response rate was 55% with a 2-year IFPS of 39%. A CLIP score 2 was associated with an inferior outcome in overall survival. Hepatic toxicities are a major determinant of the safety; the combination should be used with caution and needs further investigation. Ó 2014 Elsevier Inc.
Introduction Hepatocellular carcinoma (HCC) is a common cause of cancer mortality in Asia (1). There is great geographic heterogeneity in the incidence of HCC around the world, with most cases found in Asian countries because of the high prevalence of endemic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection (1). Most patients present with intermediate or advanced disease. Percutaneous ethanol injection, radiofrequency ablation, and transcatheter arterial chemoembolization (TACE) are generally effective for patients with 1 to 3 lesions 50%. In addition, we assumed 80% of the participants could tolerate the combined treatment.
Patient eligibility
Methods and Materials
Patients were screened at Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1; no evidence of detectable tumor beyond the liver; age older than 20 years; a life expectancy more than 3 months; underlying Child-Pugh class A disease, and laboratory results for bilirubin less than 1.5 times the upper limit of normal (ULN); aspartate aminotransferase or alanine transaminase
Radiation Oncology biology
physics
www.redjournal.org
Clinical Investigation: Gastrointestinal Cancer
Phase 2 Study of Combined Sorafenib and Radiation Therapy in Patients With Advanced Hepatocellular Carcinoma Shang-Wen Chen, MD,z,x,k Li-Ching Lin, MD,y,x Yu-Cheng Kuo, MD, PhD,z,{ Ji-An Liang, MD,z,k Chia-Chun Kuo, MD,* and Jeng-Fong Chiou, MD, PhD*,x *Department of Radiation Oncology, Taipei Medical University Hospital, Taipei, Taiwan; yDepartment of Radiation Oncology, Chi-Mei Hospital, Tainan, Taiwan; zDepartment of Radiation Oncology, China Medical University Hospital, Taichung, Taiwan; xSchool of Medicine, Taipei Medical University, Taipei, Taiwan; kSchool of Medicine, China Medical University, Taichung, Taiwan; and {Department of Biomedical Imaging and Radiological Science, China Medical University, Taichung, Taiwan Received Oct 23, 2013, and in revised form Jan 4, 2014. Accepted for publication Jan 13, 2014.
Summary The tolerance and toxicities of radiation therapy with concurrent and sequential sorafenib are acceptable in patients with hepatoma. Hepatic toxicities are a major determinant of the combined treatment. Following radiation therapy with concurrent sorafenib therapy, the complete and partial response rates were 55% with a 2-year infield progression-free survival of 39%. The Cancer of the Liver Italian Program score of 2 was associated with an inferior outcome in overall survival.
Purpose: This phase 2 study evaluated the efficacy of radiation therapy (RT) with concurrent and sequential sorafenib therapy in patients with unresectable hepatocellular carcinoma (HCC). Methods and Materials: Forty patients with unresectable HCC unfit for transarterial chemoembolization were treated with RT with concurrent and sequential sorafenib. Sorafenib was administered from the commencement of RT at a dose of 400 mg twice daily and continued to clinical or radiologic progression, unacceptable adverse events, or death. All patients had underlying Child-Pugh A cirrhosis. The maximal tumor diameter ranged from 3.0 cm to 15.5 cm. Coexisting portal vein thrombosis was found in 24 patients and was irradiated simultaneously. The cumulative RT dose ranged from 40 Gy to 60 Gy (median, 50 Gy). Image studies were done 1 month after RT and then every 3 months thereafter. Results: Thirty-three (83%) completed the allocated RT. During RT, the incidence of hand-foot skin reactions grade 2 and diarrhea were 37.5% and 25%, respectively, and 35% of patients had hepatic toxicities grade 2. Twenty-two (55.0%) patients achieved complete or partial remission at the initial assessment, and 18 (45%) had stable or progressive disease. The 2-year overall survival and infield progressionfree survival (IFPS) were 32% and 39%, respectively. A Cancer of the Liver Italian Program (CLIP) score 2 was associated with an inferior outcome in overall survival.
Reprint requests to: Jeng-Fong Chiou, MD, PhD, Department of Radiation Oncology, Taipei Medical University Hospital, Taipei; Tel: +886-227372181 ex:2130. E-mail: [email protected] This study was supported by funding from Bayer Healthcare. Conflict of interest: none. Supplementary material for this article can be found at www.redjournal.org. Int J Radiation Oncol Biol Phys, Vol. 88, No. 5, pp. 1041e1047, 2014 0360-3016/$ - see front matter Ó 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.ijrobp.2014.01.017
AcknowledgmentsdThe authors thank the following coinvestigators for their help in conducting the trial and patient care: Belle Kang and ChiaHsin Pan, Taipei Medical University Hospital, Taiwan; Ya-Ju Hsiao, China Medical University Hospital, Taiwan; Ru-Chi Lee, Chi-Mei Hospital, Taiwan. This research was supported by Bayer Healthcare Pharmaceuticals.
International Journal of Radiation Oncology Biology Physics
1042 Chen et al.
Six patients (15%) developed treatment-related hepatic toxicity grade 3 during the sequential phase, and 3 of them were fatal. Conclusions: When RT and sorafenib therapy were combined in patients with unresectable HCC, the initial complete or partial response rate was 55% with a 2-year IFPS of 39%. A CLIP score 2 was associated with an inferior outcome in overall survival. Hepatic toxicities are a major determinant of the safety; the combination should be used with caution and needs further investigation. Ó 2014 Elsevier Inc.
Introduction Hepatocellular carcinoma (HCC) is a common cause of cancer mortality in Asia (1). There is great geographic heterogeneity in the incidence of HCC around the world, with most cases found in Asian countries because of the high prevalence of endemic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection (1). Most patients present with intermediate or advanced disease. Percutaneous ethanol injection, radiofrequency ablation, and transcatheter arterial chemoembolization (TACE) are generally effective for patients with 1 to 3 lesions 50%. In addition, we assumed 80% of the participants could tolerate the combined treatment.
Patient eligibility
Methods and Materials
Patients were screened at Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1; no evidence of detectable tumor beyond the liver; age older than 20 years; a life expectancy more than 3 months; underlying Child-Pugh class A disease, and laboratory results for bilirubin less than 1.5 times the upper limit of normal (ULN); aspartate aminotransferase or alanine transaminase
