Skip to main content
Erschienen in: Clinical Drug Investigation 1/2009

01.01.2009 | Case Reports

Combination of Sorafenib and Intensity Modulated Radiotherapy for Unresectable Hepatocellular Carcinoma

verfasst von: Chen-Hsi Hsieh, Kuo-Shyang Jeng, Ching-Chung Lin, Chi-Kuan Chen, Chia-Yuan Liu, Chin-Ping Lin, Hung-Chi Tai, Chao-Hsing Wang, Pei-Wei Shueng, Dr Yu-Jen Chen

Erschienen in: Clinical Drug Investigation | Ausgabe 1/2009

Einloggen, um Zugang zu erhalten

Abstract

Unresectable hepatocellular carcinoma (HCC) has a poor therapeutic outcome. We report here on a 40-year-old male HCC patient who had undergone partial hepatectomy and was refractory to therapeutic embolization. In addition, the tumour expressed phosphorylated extracellular signal-regulated kinase and CD34. Sorafenib was administered as salvage treatment and resulted in a rapid decline in α-fetoprotein (AFP) levels. However, this was accompanied by a grade 3 skin reaction, which improved as sorafenib dosage was gradually reduced. Unfortunately, reducing the dose of sorafenib also resulted in a rebound in AFP levels and portal vein thrombosis was noted thereafter. Sorafenib 800 mg/day was resumed, but the tumour failed to respond. Intensity-modulated radiation therapy (IMRT) combined with sorafenib was administered, resulting in marked tumour shrinkage and causing recurrence of the systemic skin reaction and development of photosensitivity. The patient survived for 20 months after the start of sorafenib treatment. This case suggests that the combination of sorafenib and IMRT might provide clinical benefits in patients with HCC who express potential targets but fail to respond to sorafenib; however, skin reactions should be monitored.
Literatur
1.
Zurück zum Zitat Parkin DM, Bray F, Ferlay J, et al. Global cancer statistics, 2002. CA Cancer J Clin 2005; 55: 74–108CrossRef Parkin DM, Bray F, Ferlay J, et al. Global cancer statistics, 2002. CA Cancer J Clin 2005; 55: 74–108CrossRef
2.
Zurück zum Zitat Lavanchy D. Hepatitis B virus epidemiology, disease burden, treatment, and current and emerging prevention and control measures. J Viral Hepat 2004; 11: 97–107CrossRef Lavanchy D. Hepatitis B virus epidemiology, disease burden, treatment, and current and emerging prevention and control measures. J Viral Hepat 2004; 11: 97–107CrossRef
3.
Zurück zum Zitat Yamamoto J, Iwatsuki S, Kosuge T, et al. Should hepatomas be treated with hepatic resection or transplantation? Cancer 1999; 86: 1151–8CrossRef Yamamoto J, Iwatsuki S, Kosuge T, et al. Should hepatomas be treated with hepatic resection or transplantation? Cancer 1999; 86: 1151–8CrossRef
4.
Zurück zum Zitat Venook AP. Treatment of hepatocellular carcinoma: too many options? J Clin Oncol 1994; 12: 1323–34CrossRef Venook AP. Treatment of hepatocellular carcinoma: too many options? J Clin Oncol 1994; 12: 1323–34CrossRef
5.
Zurück zum Zitat Kim TH, Kim DY, Park JW, et al. Three-dimensional conformal radiotherapy of unresectable hepatocellular carcinoma patients for whom transcatheter arterial chemoembolization was ineffective or unsuitable. Am J Clin Oncol 2006; 29: 568–75CrossRef Kim TH, Kim DY, Park JW, et al. Three-dimensional conformal radiotherapy of unresectable hepatocellular carcinoma patients for whom transcatheter arterial chemoembolization was ineffective or unsuitable. Am J Clin Oncol 2006; 29: 568–75CrossRef
6.
Zurück zum Zitat Zhu AX. Systemic therapy of advanced hepatocellular carcinoma: how hopeful should we be? Oncologist 2006; 11: 790–800CrossRef Zhu AX. Systemic therapy of advanced hepatocellular carcinoma: how hopeful should we be? Oncologist 2006; 11: 790–800CrossRef
7.
Zurück zum Zitat Abou-Alfa GK, Schwartz L, Ricci S, et al. Phase II study of sorafenib in patients with advanced hepatocellular carcinoma. J Clin Oncol 2006; 24: 4293–300CrossRef Abou-Alfa GK, Schwartz L, Ricci S, et al. Phase II study of sorafenib in patients with advanced hepatocellular carcinoma. J Clin Oncol 2006; 24: 4293–300CrossRef
8.
Zurück zum Zitat J. Llovet, S. Ricci, V. Mazzaferro, et al. Sorafenib improves survival in advanced hepatocellular carcinoma (HCC): results of a phase III randomized placebo-controlled trial (SHARP trial). ASCO Annual Meeting Proceedings Part I. J Clin Oncol 2007; 25: 18S J. Llovet, S. Ricci, V. Mazzaferro, et al. Sorafenib improves survival in advanced hepatocellular carcinoma (HCC): results of a phase III randomized placebo-controlled trial (SHARP trial). ASCO Annual Meeting Proceedings Part I. J Clin Oncol 2007; 25: 18S
9.
Zurück zum Zitat Pugh RNH, Murray-Lyon IM, Dawson J-L, et al. Transection of the oesophagus for bleeding oesophageal varices. Br J Surg 1973; 60: 646–9CrossRef Pugh RNH, Murray-Lyon IM, Dawson J-L, et al. Transection of the oesophagus for bleeding oesophageal varices. Br J Surg 1973; 60: 646–9CrossRef
10.
Zurück zum Zitat The Cancer of the Liver Italian Program (CLIP) Investigators. A new prognostic system for hepatocellular carcinoma: a retrospective study of 435 patients. Hepatology 1998; 28: 751–5CrossRef The Cancer of the Liver Italian Program (CLIP) Investigators. A new prognostic system for hepatocellular carcinoma: a retrospective study of 435 patients. Hepatology 1998; 28: 751–5CrossRef
11.
Zurück zum Zitat Liu L, Cao Y, Chen C, et al. Sorafenib blocks the RAF/MEK/ ERK pathway, inhibits tumor angiogenesis, and induces tumor cell apoptosis in hepatocellular carcinoma model PLC/PRF/5. Cancer Res 2006; 66: 11851–8CrossRef Liu L, Cao Y, Chen C, et al. Sorafenib blocks the RAF/MEK/ ERK pathway, inhibits tumor angiogenesis, and induces tumor cell apoptosis in hepatocellular carcinoma model PLC/PRF/5. Cancer Res 2006; 66: 11851–8CrossRef
12.
Zurück zum Zitat Gollob JA, Wilhelm S, Carter C, et al. Role of Raf kinase in cancer: therapeutic potential of targeting the Raf/MEK/ERK signal transduction pathway. Semin Oncol 2006; 33: 392–406CrossRef Gollob JA, Wilhelm S, Carter C, et al. Role of Raf kinase in cancer: therapeutic potential of targeting the Raf/MEK/ERK signal transduction pathway. Semin Oncol 2006; 33: 392–406CrossRef
13.
Zurück zum Zitat Plastaras JP, Kim SH, Liu YY, et al. Cell cycle-dependent and schedule-dependent antitumor effects of sorafenib combined with radiation. Cancer Res 2007; 67: 9443–54CrossRef Plastaras JP, Kim SH, Liu YY, et al. Cell cycle-dependent and schedule-dependent antitumor effects of sorafenib combined with radiation. Cancer Res 2007; 67: 9443–54CrossRef
14.
Zurück zum Zitat Poon RT, Ng IO, Lau C, et al. Tumor microvessel density as a predictor of recurrence after resection of hepatocellular carcinoma: a prospective study. J Clin Oncol 2002; 20: 1775–85CrossRef Poon RT, Ng IO, Lau C, et al. Tumor microvessel density as a predictor of recurrence after resection of hepatocellular carcinoma: a prospective study. J Clin Oncol 2002; 20: 1775–85CrossRef
15.
Zurück zum Zitat Strumberg D, Clark JW, Awada A, et al. Safety, pharmaco-kinetics, and preliminary antitumor activity of sorafenib: a review of four phase I trials in patients with advanced refractory solid tumors. Oncologist 2007; 12: 426–37CrossRef Strumberg D, Clark JW, Awada A, et al. Safety, pharmaco-kinetics, and preliminary antitumor activity of sorafenib: a review of four phase I trials in patients with advanced refractory solid tumors. Oncologist 2007; 12: 426–37CrossRef
16.
Zurück zum Zitat Lin CS, Jen YM, Chiu SY, et al. Treatment of portal vein tumor thrombosis of hepatoma patients with either stereotactic radiotherapy or three-dimensional conformal radiotherapy. Jpn J Clin Oncol 2006; 36: 212–7CrossRef Lin CS, Jen YM, Chiu SY, et al. Treatment of portal vein tumor thrombosis of hepatoma patients with either stereotactic radiotherapy or three-dimensional conformal radiotherapy. Jpn J Clin Oncol 2006; 36: 212–7CrossRef
17.
Zurück zum Zitat Riesterer O, Honer M, Jochum W, et al. Ionizing radiation antagonizes tumor hypoxia induced by antiangiogenic treatment. Clin Cancer Res 2006; 12: 3518–24CrossRef Riesterer O, Honer M, Jochum W, et al. Ionizing radiation antagonizes tumor hypoxia induced by antiangiogenic treatment. Clin Cancer Res 2006; 12: 3518–24CrossRef
18.
Zurück zum Zitat Jones RJ, Matsui WH, Smith BD. Cancer stem cells: are we missing the target? J Natl Cancer Inst 2004; 96: 583–5CrossRef Jones RJ, Matsui WH, Smith BD. Cancer stem cells: are we missing the target? J Natl Cancer Inst 2004; 96: 583–5CrossRef
19.
Zurück zum Zitat Kasibhatla M, Steinberg P, Meyer J, et al. Radiation therapy and sorafenib: clinical data and rationale for the combination in metastatic renal cell carcinoma. Clin Genitourin Cancer 2007; 5: 291–4CrossRef Kasibhatla M, Steinberg P, Meyer J, et al. Radiation therapy and sorafenib: clinical data and rationale for the combination in metastatic renal cell carcinoma. Clin Genitourin Cancer 2007; 5: 291–4CrossRef
20.
Zurück zum Zitat Senan S, Smit EF. Design of clinical trials of radiation combined with antiangiogenic therapy. Oncologist 2007; 12: 465–77CrossRef Senan S, Smit EF. Design of clinical trials of radiation combined with antiangiogenic therapy. Oncologist 2007; 12: 465–77CrossRef
Metadaten
Titel
Combination of Sorafenib and Intensity Modulated Radiotherapy for Unresectable Hepatocellular Carcinoma
verfasst von
Chen-Hsi Hsieh
Kuo-Shyang Jeng
Ching-Chung Lin
Chi-Kuan Chen
Chia-Yuan Liu
Chin-Ping Lin
Hung-Chi Tai
Chao-Hsing Wang
Pei-Wei Shueng
Dr Yu-Jen Chen
Publikationsdatum
01.01.2009
Verlag
Springer International Publishing
Erschienen in
Clinical Drug Investigation / Ausgabe 1/2009
Print ISSN: 1173-2563
Elektronische ISSN: 1179-1918
DOI
https://doi.org/10.2165/0044011-200929010-00007

Weitere Artikel der Ausgabe 1/2009

Clinical Drug Investigation 1/2009 Zur Ausgabe