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Hepatology Research 2014
doi: 10.1111/hepr.12308
Original Article
Efficacy and safety of sorafenib in very elderly patients aged 80 years and older with advanced hepatocellular carcinoma Masayasu Jo,1,2 Kohichiroh Yasui,1 Toshihiko Kirishima,3 Toshihide Shima,4 Toshihisa Niimi,5 Takayuki Katayama,1,5 Takahiro Mori,6 Jun Funaki,7 Yoshio Sumida,1,8 Hideki Fujii,9 Shiro Takami,10 Hiroyuki Kimura,11 Yasuhide Mitsumoto,6,12 Masahito Minami,1 Kanji Yamaguchi,1 Naomi Yoshinami,3 Masayuki Mizuno,4 Rei Sendo,4,5 Saiyu Tanaka,8 Hiroyuki Shintani,3 Keizo Kagawa,5 Takeshi Okanoue4 and Yoshito Itoh1 1 Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 3Department of Gastroenterology, Kyoto City Hospital, 7Department of Gastroenterology, Koseikai Takeda Hospital, 9Department of Internal Medicine, Aiseikai Yamashina Hospital, 11 Department of Gastroenterology, Japanese Red Cross Kyoto Daiichi Hospital, 12Department of Gastroenterology, Social Insurance Kyoto Hospital, Kyoto, 2Department of Molecular Gastroenterology and Hepatology, North Medical Center Kyoto Prefectural University of Medicine, Yosano, 4Department of Gastroenterology and Hepatology, Saiseikai Suita Hospital, Suita, 5Department of Gastroenterology, Fukuchiyama City Hospital, Fukuchiyama, 6Department of Gastroenterology, Osaka General Hospital of West Japan Railway Company, Osaka, 8Center for Digestive and Liver Diseases, Nara City Hospital, Nara, and 10 Department of Gastroenterology, Otsu Municipal Hospital, Japan
Aim: Sorafenib is the standard systemic therapy for patients with advanced hepatocellular carcinoma (HCC). We aimed to assess the efficacy and safety of sorafenib therapy in very elderly patients aged 80 years and older with advanced HCC. Methods: In a retrospective multicenter study in Japan, we reviewed 185 patients (median age, 71 years; 82% male; 95% Child–Pugh class A) with advanced HCC who received sorafenib therapy. Data were compared between 24 (13%) patients aged 80 years and older and 161 (87%) patients aged less than 80 years. We used propensity score matching to adjust for differences between the two groups. Results: Median overall survival was 10.6 months in all
10.5 months in those aged less than 80 years. There were no significant differences in overall survival, tumor response, and frequency and severity of drug-related adverse events between patients aged 80 years and older and those aged less than 80 years in both the entire study cohort and the propensity-matched cohort.
Conclusion: Sorafenib may be effective and well tolerated, even in patients with advanced HCC who are aged 80 years and older, as well as those aged less than 80 years. Key words: elderly patient, hepatocellular carcinoma, sorafenib
patients: 11.7 months in patients aged 80 years and older and
INTRODUCTION
H
EPATOCELLULAR CARCINOMA (HCC) is the fifth most common cancer worldwide and the
Correspondence: Dr Kohichiroh Yasui, Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto 602-8566, Japan. Email: [email protected]; [email protected] Received 2 September 2013; revision 16 January 2014; accepted 29 January 2014.
© 2014 The Japan Society of Hepatology
third most common cause of cancer mortality.1 Although the global age distribution of HCC varies by geographic region, sex and etiology, the incidence of HCC generally increases with age. In Europe and the USA, the highest age-specific rates are found among persons aged 75 years and older.1 In Japan, the proportion of elderly patients with HCC is increasing.2 Potentially curative treatments for HCC include hepatic resection, liver transplantation and local ablation (radiofrequency ablation). However, the recurrence rate of HCC after successful initial treatment is high. Moreover, many patients with HCC are unsuitable for
1
2 M. Jo et al.
curative treatment at the time of initial diagnosis due to advanced cancer stage. HCC patients with advanced stage disease or with progression after initial treatment have a poor prognosis. Sorafenib, an oral multikinase inhibitor of the vascular endothelial growth factor receptor, the plateletderived growth factor receptor and Raf, is the only approved systemic therapy for patients with advanced HCC.3 Sorafenib inhibits tumor cell proliferation and tumor angiogenesis. Although sorafenib has been shown to improve overall survival and to be well tolerated in advanced stage HCC patients with wellpreserved liver function (i.e. Child–Pugh class A),4,5 its efficacy and safety are not well established for elderly patients, especially for very elderly patients (defined in the present study as those aged 380 years). Sorafenib therapy in very elderly patients appears to be more complicated than in younger patients because very elderly patients have reduced function of vital organs, multiple coexisting diseases (comorbidities), polypharmacy, altered pharmacokinetics and physical disability. In the present study, we aimed to assess the efficacy and safety of sorafenib therapy in patients aged 80 years and older with advanced HCC. We performed a retrospective multicenter study and compared overall survival, tumor response, treatment compliance, and frequency and severity of adverse events between patients aged 80 years and older and those aged less than 80 years.
METHODS
Hepatology Research 2014
aminotransferase [AST] levels
Hepatology Research 2014
doi: 10.1111/hepr.12308
Original Article
Efficacy and safety of sorafenib in very elderly patients aged 80 years and older with advanced hepatocellular carcinoma Masayasu Jo,1,2 Kohichiroh Yasui,1 Toshihiko Kirishima,3 Toshihide Shima,4 Toshihisa Niimi,5 Takayuki Katayama,1,5 Takahiro Mori,6 Jun Funaki,7 Yoshio Sumida,1,8 Hideki Fujii,9 Shiro Takami,10 Hiroyuki Kimura,11 Yasuhide Mitsumoto,6,12 Masahito Minami,1 Kanji Yamaguchi,1 Naomi Yoshinami,3 Masayuki Mizuno,4 Rei Sendo,4,5 Saiyu Tanaka,8 Hiroyuki Shintani,3 Keizo Kagawa,5 Takeshi Okanoue4 and Yoshito Itoh1 1 Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 3Department of Gastroenterology, Kyoto City Hospital, 7Department of Gastroenterology, Koseikai Takeda Hospital, 9Department of Internal Medicine, Aiseikai Yamashina Hospital, 11 Department of Gastroenterology, Japanese Red Cross Kyoto Daiichi Hospital, 12Department of Gastroenterology, Social Insurance Kyoto Hospital, Kyoto, 2Department of Molecular Gastroenterology and Hepatology, North Medical Center Kyoto Prefectural University of Medicine, Yosano, 4Department of Gastroenterology and Hepatology, Saiseikai Suita Hospital, Suita, 5Department of Gastroenterology, Fukuchiyama City Hospital, Fukuchiyama, 6Department of Gastroenterology, Osaka General Hospital of West Japan Railway Company, Osaka, 8Center for Digestive and Liver Diseases, Nara City Hospital, Nara, and 10 Department of Gastroenterology, Otsu Municipal Hospital, Japan
Aim: Sorafenib is the standard systemic therapy for patients with advanced hepatocellular carcinoma (HCC). We aimed to assess the efficacy and safety of sorafenib therapy in very elderly patients aged 80 years and older with advanced HCC. Methods: In a retrospective multicenter study in Japan, we reviewed 185 patients (median age, 71 years; 82% male; 95% Child–Pugh class A) with advanced HCC who received sorafenib therapy. Data were compared between 24 (13%) patients aged 80 years and older and 161 (87%) patients aged less than 80 years. We used propensity score matching to adjust for differences between the two groups. Results: Median overall survival was 10.6 months in all
10.5 months in those aged less than 80 years. There were no significant differences in overall survival, tumor response, and frequency and severity of drug-related adverse events between patients aged 80 years and older and those aged less than 80 years in both the entire study cohort and the propensity-matched cohort.
Conclusion: Sorafenib may be effective and well tolerated, even in patients with advanced HCC who are aged 80 years and older, as well as those aged less than 80 years. Key words: elderly patient, hepatocellular carcinoma, sorafenib
patients: 11.7 months in patients aged 80 years and older and
INTRODUCTION
H
EPATOCELLULAR CARCINOMA (HCC) is the fifth most common cancer worldwide and the
Correspondence: Dr Kohichiroh Yasui, Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto 602-8566, Japan. Email: [email protected]; [email protected] Received 2 September 2013; revision 16 January 2014; accepted 29 January 2014.
© 2014 The Japan Society of Hepatology
third most common cause of cancer mortality.1 Although the global age distribution of HCC varies by geographic region, sex and etiology, the incidence of HCC generally increases with age. In Europe and the USA, the highest age-specific rates are found among persons aged 75 years and older.1 In Japan, the proportion of elderly patients with HCC is increasing.2 Potentially curative treatments for HCC include hepatic resection, liver transplantation and local ablation (radiofrequency ablation). However, the recurrence rate of HCC after successful initial treatment is high. Moreover, many patients with HCC are unsuitable for
1
2 M. Jo et al.
curative treatment at the time of initial diagnosis due to advanced cancer stage. HCC patients with advanced stage disease or with progression after initial treatment have a poor prognosis. Sorafenib, an oral multikinase inhibitor of the vascular endothelial growth factor receptor, the plateletderived growth factor receptor and Raf, is the only approved systemic therapy for patients with advanced HCC.3 Sorafenib inhibits tumor cell proliferation and tumor angiogenesis. Although sorafenib has been shown to improve overall survival and to be well tolerated in advanced stage HCC patients with wellpreserved liver function (i.e. Child–Pugh class A),4,5 its efficacy and safety are not well established for elderly patients, especially for very elderly patients (defined in the present study as those aged 380 years). Sorafenib therapy in very elderly patients appears to be more complicated than in younger patients because very elderly patients have reduced function of vital organs, multiple coexisting diseases (comorbidities), polypharmacy, altered pharmacokinetics and physical disability. In the present study, we aimed to assess the efficacy and safety of sorafenib therapy in patients aged 80 years and older with advanced HCC. We performed a retrospective multicenter study and compared overall survival, tumor response, treatment compliance, and frequency and severity of adverse events between patients aged 80 years and older and those aged less than 80 years.
METHODS
Hepatology Research 2014
aminotransferase [AST] levels
