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Time to Progression of AFP (TPA) as a Predictor of Survival in Hepatocellular Carcinoma Treated with Sorafenib (SOR)

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DOI: 10.4236/jct.2014.514133    3,590 Downloads   4,014 Views   Citations

ABSTRACT

Background: The standard therapy in advanced hepatocellular carcinoma (HCC) is sorafenib (SOR), which has the inconvenience of toxicity and discontinuation. Patient selection and the use of early markers are critical for optimizing the potential benefit of SOR. Alpha-fetoprotein (AFP) has an established role in HCC prognosis. The objective was to evaluate whether AFP variation during SOR treatment reflects the lack of progression to SOR and can be used as a prognostic factor. Methods: AFP levels were prospectively analyzed in 114 patients to determine whether the time to progression of AFP (TPA) at 3 months had a prognostic value for survival. Results: Between July 2007 and October 2012, 114 patients were included (mean age 64 years, 97 male, 96 with cirrhosis). Etiology was alcohol 47 (41%) and hepatitis C virus (HCV) 31 (27%). According to the Barcelona Clinic Liver Cancer (BCLC) staging system: A (one case), B (24 cases) and C (89 cases). The Child-Pugh was Class A in 89 cases. The general condition of the patient according to ECOG-PS was 0 in 73 cases. The median duration of treatment was 5 months (3.47 - 6.53, 95% CI). The median overall survival (OS) was 9.23 months. The standard dose was maintained in 26 patients (22.8%). Sixty-seven percent of patients experienced at least one adverse event grade 3-4. The time to progression of AFP lower or higher than 3 months was an independent prognostic factor of OS (univariate and multivariate analysis): 8.10 vs. 18.85 months, P < 0.001. Conclusion: HCC treated with SOR with TPA > 3 months had longer OS, and TPA was an independent prognostic factor.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

Varela, M. , Castaño-Fernández, O. , Garrido, M. , Blanco-García, L. , Martínez-Camblor, P. , Mesa-Álvarez, A. , Navascués, C. , Cadahía-Rodrigo, V. , Llano, R. , Pérez-Álvarez, R. , González-Diéguez, M. and Rodríguez, M. (2014) Time to Progression of AFP (TPA) as a Predictor of Survival in Hepatocellular Carcinoma Treated with Sorafenib (SOR). Journal of Cancer Therapy, 5, 1332-1343. doi: 10.4236/jct.2014.514133.

References

[1] Ferlay, J., Shin, H.R., Bray, F., Forman, D., Mathers, C. and Parkin, D.M. (2010) Estimates of Worldwide Burden of Cancer in 2008: GLOBOCAN 2008. International Journal of Cancer, 127, 2893-2917. http://dx.doi.org/10.1002/ijc.25516
[2] Llovet, J.M., Ricci, S., Mazzaferro, V., Hilgard, P., Gane, E., Blanc, J.F., de Oliveira, A.C., Santoro, A., Raoul, J.L., Forner, A., Schwartz, M., Porta, C., Zeuzem, S., Bolondi, L., Greten, T.F., Galle, P.R., Seitz, J.F., Borbath, I., H?ussinger, D., Giannaris, T., Shan, M., Moscovici, M., Voliotis, D. and Bruix, J., SHARP Investigators Study Group (2008) Sorafenib in Advanced Hepatocellular Carcinoma. The New England Journal of Medicine, 359, 378-390. http://dx.doi.org/10.1056/NEJMoa0708857
[3] Cheng, A.L., Kang, Y.K., Chen, Z., Tsao, C.J., Qin, S., Kim, J.S., Luo, R., Feng, J., Ye, S., Yang, T.S., Xu, J., Sun, Y., Liang, H., Liu, J., Wang, J., Tak, W.Y., Pan, H., Burock, K., Zou, J., Voliotis, D. and Guan, Z. (2009) 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. The Lancet Oncology, 10, 25-34. http://dx.doi.org/10.1016/S1470-2045(08)70285-7
[4] Cheng, A.L., Kang, Y.K., Lin, D.Y., Park, J.W., Kudo, M., Qin, S., Chung, H.C., Song, X., Xu, J., Poggi, G., Omata, M., Lowenthal, S.P., Lanzalone, S., Yang, L., Lechuga, M.J. and Raymond, E. (2013) Sunitinib versus Sorafenib in Advanced Hepatocellular Cancer: Results of a Randomized Phase III Trial. Journal of Clinical Oncology, 31, 4067-4075. http://dx.doi.org/10.1200/JCO.2012.45.8372
[5] Johnson, P.J., Qin, S., Park, J.W., Poon, R.T., Raoul, R.J., Philip, A., Hsu, C.H., Hu, T.H., Heo, J., Xu, J., Lu, L., Chao, Y., Boucher, E., Han, K.H., Paik, S.W., Robles-Avi?a, J., Kudo, M., Yan, L., Sobhonslidsuk, A., Komov, D., Decaens, T., Tak, W.Y., Jeng, L.B., Liu, D., Ezzeddine, R., Walters, I. and Cheng, A.L. (2013) Brivanib versus Sorafenib as First-Line Therapy in Patients with Unresectable, Advanced Hepatocellular Carcinoma: Results from the Randomized Phase III BRISK-FL Study. Journal of Clinical Oncology, 31, 3517-3524. http://dx.doi.org/10.1200/JCO.2012.48.4410
[6] Cainap, C., Qin, S., Huang, W.T., Chung, I.J., Pan, H., Cheng, Y., Kudo, M., Kang, Y.K., Chen, P.J., Toh, H.C., Gorbunova, V., Eskens, F., Qian, J., McKee, M.D., Ricker, J.L., Carlson, D.M. and Nowiem, S.E. (2013) Phase III Trial of Linifanib versus Sorafenib in Patients with Advanced Hepatocellular Carcinoma (HCC). Journal of Clinical Oncology, 31, 249.
[7] Zhu, A.X., Rosmorduc, O., Evans, J., Ross, P., Santoro, A., Carrilho, F.J., Leberre, M.-A., Jensen, M., Meinhardt, G. and Kang, Y.K. (2012) A Phase III, Randomized, Double-Blind, Placebo-Controlled Trial of Sorafenib plus Erlotinib in Patients with Hepatocellular Carcinoma (HCC). Annals of Oncology, 23, 9.
[8] Llovet, J.M., Decaens, T., Raoul, J.L., Boucher, E., Kudo, M., Chang, C., Kang, Y.K., Assenat, E., Lim, H.Y., Boige, V., Mathurin, P., Fartoux, L., Lin, D.Y., Bruix, J., Poon, R.T., Sherman, M., Blanc, J.F., Finn, R.S., Tak, W.Y., Chao, Y., Ezzeddine, R., Liu, D., Walters, I. and Park, J.W. (2013) Brivanib in Patients With Advanced Hepatocellular Carcinoma Who Were Intolerant to Sorafenib or for Whom Sorafenib Failed: Results from the Randomized Phase III BRISK-PS Study. Journal of Clinical Oncology, 31, 3509-3516. http://dx.doi.org/10.1200/JCO.2012.47.3009
[9] Zhu, A.X., Kudo, M., Assenat, E., Cattan, S., Kang, Y.K., Lim, H.Y., Poon, R.T., Blanc, J.F., Vogel, A., Chen, C.L., Dorval, E., Peck-Radosavljevic, M., Santoro, A., Daniele, B., Furuse, J., Jappe, A., Perraud, K., Anak, O., Sellami, D.B. and Chen, L.T. (2014) Effect of Everolimus on Survival in Advanced Hepatocellular Carcinoma after Failure of Sorafenib: The EVOLVE-1 Randomized Clinical Trial. JAMA, 312, 57-67.
[10] Reig, M., Torres, F., Rodriguez-Lope, C., Forner, A., Llarch, N., Rimola, J., Darnell, A., Ríos, J., Ayuso, C. and Bruix, J. (2014) Early Dermatologic Adverse Events Predict Better Outcome in HCC Patients Treated with Sorafenib. Journal of Hepatology, 14, 211-216.
[11] Nojiri, S., Kusakabe, A., Fujiwara, K., Shinkai, N., Matsuura, K., Iio, E., Miyaki, T., Nomura, T., Sobue, S., Sano, H., Hasegawa, I., Ohno, T., Takahashi, Y., Orito, E. and Joh, T. (2012) Clinical Factors Related to Long-Term Administration of Sorafenib in Patients with Hepatocellular Carcinoma. Cancer Management and Research, 4, 423-429. http://dx.doi.org/10.2147/CMAR.S38684
[12] Llovet, J.M., Pe?a, C.E. and Lathia, C.D., SHARP Investigators Study Group (2012) Plasma Biomarkers as Predictors of Outcome in Patients with Advanced Hepatocellular Carcinoma. Clinical Cancer Research, 18, 2290-2300. http://dx.doi.org/10.1158/1078-0432.CCR-11-2175
[13] Memon, K., Kulik, L., Lewandowski, R.J., Wang, E., Ryu, R.K., Riaz, A,, Nikolaidis, P., Miller, F.H., Yaghmai, V., Baker, T., Abecassis, M., Benson, A.B., Mulcahy, M.F., Omary, R.A. and Salem, R. (2012) α-Fetoprotein Response Correlates with EASL Response and Survival in Solitary Hepatocellular Carcinoma Treated with Transarterial Therapies: A Subgroup Analysis. Journal of Hepatology, 56, 1112-1120. http://dx.doi.org/10.1016/j.jhep.2011.11.020
[14] Vora, S.R., Zheng, H., Stadler, Z.K., Fuchs, S.C. and Zhu, A.X. (2009) Serum α-Fetoprotein Response as a Surrogate for Clinical Outcome in Patients Receiving Systemic Therapy for Advanced Hepatocellular Carcinoma. The Oncologist, 14, 717-725.
http://dx.doi.org/10.1634/theoncologist.2009-0038
[15] Chen, L.T., Liu, T.W., Chao, Y., Shiah, H.S., Chang, J.Y., Juang, S.H., Chen, S.C., Chuang, T.R., Chin, Y.H. and Whang-Peng, J. (2005) α-Fetoprotein Response Predicts Survival Benefits of Thalidomide in Advanced Hepatocellular Carcinoma. Alimentary Pharmacology & Therapeutics, 22, 217-226.
http://dx.doi.org/10.1111/j.1365-2036.2005.02547.x
[16] Chan, S.L., Mo, F.K., Johnson, P.J., Hui, E.P., Ma, B.B., Ho, W.M., Lam, K.C., Chan, A.T., Mok, T.S. and Yeo, W. (2009) New Utility of an Old Marker: Serial α-Fetoprotein Measurement in Predicting Radiologic Response and Survival of Patients with Hepatocellular Carcinoma Undergoing Systemic Chemotherapy. Journal of Clinical Oncology, 27, 446-452.
http://dx.doi.org/10.1200/JCO.2008.18.8151
[17] Shao, Y.Y., Lin, Z.Z., Hsu, C., Shen, Y.C., Hsu, C.H. and Cheng, A.L. (2010) Early α-Fetoprotein Response Predicts Treatment Efficacy of Antiangiogenic Systemic Therapy in Patients with Advanced Hepatocellular Carcinoma. Cancer, 116, 4590-4596. http://dx.doi.org/10.1002/cncr.25257
[18] Yau, T., Yao, T.J., Chan, P., Ng, K., Fan, S.T. and Poon, R.T. (2008) A New Prognostic Score System in Patients with Advanced Hepatocellular Carcinoma Not Amendable to Locoregional Therapy: Implication for Patient Selection in Systemic Therapy Trials. Cancer, 113, 2742-2751.
http://dx.doi.org/10.1002/cncr.23878
[19] Personeni, N., Bozzarelli, S., Pressiani, T., Rimassa, L., Tronconi, M.C., Sclafani, F., Carnaghi, C., Pedicini, V., Giordano, L. and Santoro, A. (2012) Usefulness of α-Fetoprotein Response in Patients Treated with Sorafenib for Advanced Hepatocellular Carcinoma. Journal of Hepatology, 57, 101-107. http://dx.doi.org/10.1016/j.jhep.2012.02.016
[20] Kawaoka, T., Aikata, H., Murakami, E., Nakahara, T., Naeshiro, N., Tanaka, M., Honda, Y., Miyaki, D., Nagaoki, Y., Takaki, S., Hiramatsu, A., Waki, K., Takahashi, S. and Chayama, K. (2012) Evaluation of the mRECIST and α-Fetoprotein Ratio for Stratification of the Prognosis of Advanced-Hepatocellular-Carcinoma Patients Treated with Sorafenib. Oncology, 83, 192-200.
http://dx.doi.org/10.1159/000341347
[21] Nakazawa, T., Hidaka, H., Takada, J., Okuwaki, Y., Tanaka, Y., Watanabe, M., Shibuya, A., Minamino, T., Kokubu, S. and Koizumi, W. (2013) Early Increase in α-Fetoprotein for Predicting Unfavorable Clinical Outcomes in Patients with Advanced Hepatocellular Carcinoma Treated with Sorafenib. European Journal of Gastroenterology & Hepatology, 25, 683-689.
http://dx.doi.org/10.1097/MEG.0b013e32835d913b
[22] Okuwaki, Y., Nakazawa, T., Hidaka, H., Shibuya, A. and Koizumi, W. (2012) Late-Onset Benefit in Progressive Advanced Hepatocellular Carcinoma with Continued Sorafenib Therapy: A Case Report. Journal of Medical Case Reports, 6, 38. http://dx.doi.org/10.1186/1752-1947-6-38
[23] European Association for the Study of the Liver; European Organisation for Research and Treatment of Cancer (2012) EASL-EORTC Clinical Practice Guidelines: Management of Hepatocellular Carcinoma. Journal of Hepatology, 56, 908-943.
[24] Zhang, L., Bhasin, M., Schor-Bardach, R., Wang, X., Collins, M.P., Panka, D., Putheti, P., Signoretti, S., Alsop, D.C., Libermann, T., Atkins, M.B., Mier, J.W., Goldberg, S.N. and Bhatt, R.S. (2011) Resistance of Renal Cell Carcinoma to Sorafenib Is Mediated by Potentially Reversible Gene Expression. PLoS ONE, 6, e19144. http://dx.doi.org/10.1371/journal.pone.0019144
[25] Naito, S., Tsukamoto, T., Murai, M., Fukino, K. and Akaza, H. (2011) Overall Survival and Good Tolerability of Long-Term Use of Sorafenib after Cytokine Treatment: Final Results of a Phase II Trial of Sorafenib in Japanese Patients with Metastatic Renal Cell Carcinoma. BJU International, 108, 1813-1819. http://dx.doi.org/10.1111/j.1464-410X.2011.10281.x
[26] Kang, Y.K., Ryu, M.H., Yoo, C., Ryoo, B.Y., Kim, H.J., Lee, J.J., Nam, B.H., Ramaiya, N., Jagannathan, J. and Demetri, G.D. (2013) Resumption of Imatinib to Control Metastatic or Unresectable Gastrointestinal Stromal Tumours after Failure of Imatinib and Sutinib (RIGHT): A Randomized, Placebo-Controlled, Phase 3 Trial. The Lancet Oncology, 14, 1175-1182.
http://dx.doi.org/10.1016/S1470-2045(13)70453-4
[27] Nakao, K. and Ichikawa, T. (2013) Recent Topics on α-Fetoprotein. Hepatology Research, 43, 820-825. http://dx.doi.org/10.1111/hepr.12052
[28] Shin, S.Y. and Lee, Y.J. (2013) Correlation of Skin Toxicity and Hypertension with Clinical Benefit in Advanced Hepatocellular Carcinoma Patients Treated with Sorafenib. International Journal of Clinical Pharmacology and Therapeutics, 51, 837-846. http://dx.doi.org/10.5414/CP201907

  
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