Sorafenib in the Treatment of Recurrent Hepatocellular Carcinoma after Liver Transplantation: A Report of Four Cases

Young Mi Hong; Ki Tae Yoon; Mong Cho; Dae Hwan Kang; Hyung Wook Kim; Cheol Woong Choi; Su Bum Park; Jeong Heo; Hyun Young Woo; Won Lim

doi:10.4166/kjg.2015.65.4.246

Journal List > Korean J Gastroenterol > v.65(4) > 1007362

Go to TopGo to Top Go to BottomGo to Bottom

TOOLS

Hong, Yoon, Cho, Kang, Kim, Choi, Park, Heo, Woo, and Lim: Sorafenib in the Treatment of Recurrent Hepatocellular Carcinoma after Liver Transplantation: A Report of Four Cases

Case Report

Korean J Gastroenterol 2015;65(4):246-251.

Published online: 4 October 2015

DOI: https://doi.org/10.4166/kjg.2015.65.4.246

Sorafenib in the Treatment of Recurrent Hepatocellular Carcinoma after Liver Transplantation: A Report of Four Cases

Young Mi Hong^1,^3,⁴, Ki Tae Yoon^1,^3,⁴, Mong Cho^1,^3,⁴, Dae Hwan Kang^1,^3,⁴, Hyung Wook Kim^1,^3,⁴, Cheol Woong Choi^1,^3,⁴, Su Bum Park^1,^3,⁴, Jeong Heo^2,³, Hyun Young Woo^2,³, Won Lim^2,³

¹Department of Internal Medicine, Pusan National University Yangsan Hospital, Yangsan, Korea

²Department of Internal Medicine, Pusan National University Hospital, Busan, Korea

³Department of Internal Medicine, Pusan National University School of Medicine, Yangsan, Korea

⁴Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Korea

Correspondence to: Ki Tae Yoon, Department of Internal Medicine, Pusan National University Yangsan Hospital, 20 Geumo-ro, Mulgeum-eup, Yangsan 626-770, Korea. Tel: +82-55-360-2362, Fax: +82-55-360-1737, E-mail: ktyoon@pusan.ac.kr

Received 27 July 201416 September 2014 Accepted 19 September 2014

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

With an increasing number of patients with hepatocellular carcinoma (HCC) undergoing liver transplantation (LT), tumor recurrence remains the main limiting factor for long-term survival. Although sorafenib is available for advanced HCC, there is still a lack of data on the use of sorafenib for treatment of recurrent HCC after LT. Here, we report on four cases of the use of sorafenib for treatment of recurrent HCC after LT. The median time of recurrence from LT was 4 months (range, 1–16 months). Two of the four evaluated patients showed stable disease, which was the best response and the duration of stabilization was 11 months and 5 months, respectively. One patient also experienced stable disease and remained in stable disease without sorafenib therapy for 29 months and the total duration of stabilization was 38 months. The remaining patient showed partial response but stopped treatment due to radiological tumor progression during treatment. Although all cases were high risk group for recurrence such as above Milan criteria, vascular invasion and tumor biology, clinical outcomes showed some good results. Therefore, sorafenib may be an acceptable treatment option for recurrent HCC after LT.

Keywords: Hepatocellular carcinoma, Liver transplantation, Recurrence, Sorafenib

References

1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011; 61:69–90.

2. Llovet JM, Fuster J, Bruix J. Barcelona-Clínic Liver Cancer Group. The Barcelona approach: diagnosis, staging, and treatment of hepatocellular carcinoma. Liver Transpl. 2004; 10(2 Suppl 1):S115–S120.

3. Cheng AL, Kang YK, Chen Z, et al. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2009; 10:25–34.

4. Llovet JM, Burroughs A, Bruix J. Hepatocellular carcinoma. Lancet. 2003; 362:1907–1917.

5. Mazzaferro V, Regalia E, Doci R, et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med. 1996; 334:693–699.

6. Mazzaferro V, Llovet JM, Miceli R, et al. Metroticket Investigator Study Group. Predicting survival after liver transplantation in patients with hepatocellular carcinoma beyond the Milan criteria: a retrospective, exploratory analysis. Lancet Oncol. 2009; 10:35–43.

7. Yao FY, Ferrell L, Bass NM, et al. Liver transplantation for hepatocellular carcinoma: expansion of the tumor size limits does not adversely impact survival. Hepatology. 2001; 33:1394–1403.

8. DuBay D, Sandroussi C, Sandhu L, et al. Liver transplantation for advanced hepatocellular carcinoma using poor tumor differentiation on biopsy as an exclusion criterion. Ann Surg. 2011; 253:166–172.

9. Guiteau JJ, Cotton RT, Washburn WK, et al. An early regional experience with expansion of Milan Criteria for liver transplant recipients. Am J Transplant. 2010; 10:2092–2098.

10. Duffy JP, Vardanian A, Benjamin E, et al. Liver transplantation criteria for hepatocellular carcinoma should be expanded: a 22-year experience with 467 patients at UCLA. Ann Surg. 2007; 246:502–509. discussion 509–511.

11. Wilhelm S, Carter C, Lynch M, et al. Discovery and development of sorafenib: a multikinase inhibitor for treating cancer. Nat Rev Drug Discov. 2006; 5:835–844.

12. Llovet JM, Ricci S, Mazzaferro V, et al. SHARP Investigators Study Group. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008; 359:378–390.

13. Bhoori S, Toffanin S, Sposito C, et al. Personalized molecular tar-geted therapy in advanced, recurrent hepatocellular carcinoma after liver transplantation: a proof of principle. J Hepatol. 2010; 52:771–775.

14. Lee JO, Kim DY, Lim JH, et al. Palliative chemotherapy for patients with recurrent hepatocellular carcinoma after liver transplantation. J Gastroenterol Hepatol. 2009; 24:800–805.

15. Wang Y, Speeg KV, Washburn WK, Halff G. Sirolimus plus sorafenib in treating HCC recurrence after liver transplantation: a case report. World J Gastroenterol. 2010; 16:5518–5522.

16. Yoon DH, Ryoo BY, Ryu MH, et al. Sorafenib for recurrent hepatocellular carcinoma after liver transplantation. Jpn J Clin Oncol. 2010; 40:768–773.

17. Waidmann O, Hofmann WP, Zeuzem S, Trojan J. mTOR inhibitors and sorafenib for recurrent heptocellular carcinoma after ortho-topic liver transplantation. J Hepatol. 2011; 54:396–398.

18. Sposito C, Mariani L, Germini A, et al. Comparative efficacy of sorafenib versus best supportive care in recurrent hepatocellular carcinoma after liver transplantation: a case-control study. J Hepatol. 2013; 59:59–66.

19. Waghray A, Balci B, El-Gazzaz G, et al. Safety and efficacy of sorafenib for the treatment of recurrent hepatocellular carcinoma after liver transplantation. Clin Transplant. 2013; 27:555–561.

20. Alsina AE, Makris A, Nenos V, et al. Can sorafenib increase survival for recurrent hepatocellular carcinoma after liver transplantation? A pilot study. Am Surg. 2014; 80:680–684.

Fig. 1.

(A-D) The radiologic features of Case 1. (A, B) Chest CT showed multiple lung nodules on both lobes (arrows) before sorafenib treatment.(C, D) Two months after sorafenib administration, chest CT showed that the majority of variable sized multiple nodules on both lungs (arrows) had disappeared and some indeterminate nodules remained. (E-H) The radiologic features of Case 2. Chest CT (E, F) showed a 19 mm sized dense round nodule (arrows) in the right lower lobe (RLL) and a 3 mm sized indeterminate nodule in the left upper lobe (LUL). (G) PET-CT also showed a hypermetabolic nodule (SUVmax 3.4) on RLL (arrow). (H) Two months after sorafenib administration, chest CT showed no interval change of lung nodule in LUL (arrow).

Fig. 2.

(A-D) The radiologic features of Case 3. (A, B) Chest CT showed variable sized multiple nodules on both lungs (largest, 12 mm) (arrows) before sorafenib treatment. (C, D) Five months after sorafenib administration, chest CT revealed that several variable sized multiple nodules on both lungs had decreased and some nodules remained (arrows). (E-H) The radiologic features of Case 4. (E) Abdomen CT showed an enhancing mass (4.0×2.9 cm) at the right acetabulum. (F, G) Bone scan and PET-CT also showed bone metastasis in the right pelvic bone. (H) Three month after sorafenib administration, abdomen CT showed interval decrease in the size of metastasis at the right acetabulum.

Table 1.

Demographics and Clinical Characteristics of the Patients

Patient No.	Gender/age (yr)	Milan criteria	preLT AFP (ng/mL)	preLT PIVKA-II (mAU/mL)	MELD score	preLT PET uptake	Microvascular invasion	Macrovascular invasion	Patholigic differentiation	^Recurrence	Time to recurrence
1	M/54	Beyond	150.4	>2,000	26	Uptake	Yes	Yes	II/III	Lung	5
2	F/57	Within	80.98	59	11	Uptake	Yes	No	IV/III	Lung	16
3	M/58	Beyond	481.9	692	11	Uptake	No	No	IIL/II	Lung	4
4	M/51	Within	2,957	995	22	NA	No	No	II/III	Bone	1

preLT, before liver transplantation; PIVKA-II, vitamin K absence or antagonist II; MELD, model for end-stage liver disease; NA, not applicable.

Table 2.

Characteristics of Patients Treated with Sorafenib for Recurrent Hepatocellular Carcinoma after Liver Transplantation

Patient No.	Gender/age (yr)	Immunosuppressants	Dose of sorafenib (mg)	Significant toxicities	AFP at recurrence (ng/mL)	Nadir AFP after sorafenib (ng/mL)	Best response	Follow up peroid from recurrence (mo)	Total time of sorafenib use (mo)	Current status
1	M/54	Cyclosporin A+ MMF	400 (bid)	Diarrhea	46.9	2.42	SD	38	9	Alive
			→200 (bid)	G3
2	F/57	Tacrolimus+ MMF	400 (bid)	Alopecia	2.91	1.47	SD	21	19	Alive
		→ Cyclosporin+ MMF
3	M/58	Tacrolimus+ MMF	400 (bid)	HFSR G2	30.1	15.47	SD	23	5	Alive
		→ Tacrolimus
4	M/51	Tacrolimus→	400 (bid)	HFSR G3	180	22.92	PR	14	12	-
		Tacrolimus+ silorimus	→400 (qd)

MMF, mycophenolate mofetil; bid, twice daily; qd, daily; HFSR, hand-foot skin reaction; SD, stable disease; PR, partial response.

TOOLS

Similar articles