Share This Article:

Crizotinib in non-small cell lung cancer

DOI: 10.4236/mc.2014.31002    3,305 Downloads   6,648 Views  

ABSTRACT

Chemotherapy and targeted therapy remain the cornerstone of treatment of locally advanced and metastatic non-small cells lung cancer (NSCLC). Given the intrinsic chemoresistance of tumor cells, new treatment options have been developped. The knowledge of the molecular mechanisms of tumor biology, and signal transduction pathways activating cancer cells led to the identification of a new targeted therapy such as Crizotinib. The small molecule Crizotinib is a selective inhibitor of the receptor tyrosine kinase ALK (anaplastic lymphoma kinase) and its oncogenic variants (ALK fusion gene and some mutations of ALK). Phases I and II trials showed the efficacy of Crizotinib in the treatment of locally advanced and metastatic NSCLC expressing ALK. Thereafter, randomized Phase III trial confirmed the significant superiority of Crizotinib versus standard chemotherapy in terms of progression free survival and objective response with good tolerance; therefore, it has been approved by the Food and Drug Administration (FDA) as the standard treatment for locally advanced and metastatic ALK-positive NSCLC.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

Mellas, N. , Hijri, F. , Benbrahim, Z. , Mesbahi, O. and Ismaili, N. (2014) Crizotinib in non-small cell lung cancer. Modern Chemotherapy, 3, 5-9. doi: 10.4236/mc.2014.31002.

References

[1] Scagliotti, G.V., Parikh, P., Von Pawel, J., Biesma, B., Vansteenkiste, J., Manegold, C., Serwatowski, P., Gatzemeier, U., Digumarti, R., Zukin, M., Lee, J.S., Mellemgaard, A., Park, K., Patil, S., Rolski, J., Goksel, T., de Marinis, F., Simms, L., Sugarman, K.P. and Gandara, D. (2008) Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. Journal of Clinical Oncology, 26, 3543-3551.
http://dx.doi.org/10.1200/JCO.2007.15.0375
[2] Shepherd, F.A., Rodrigues, P.J., Ciuleanu, T., Tan, E.H., Hirsh, V., Thongprasert, S., Campos, D., Maoleekoonpiroj, S., Smylie, M., Martins, R., van Kooten, M., Dediu, M., Findlay, B., Tu, D., Johnston, D., Bezjak, A., Clark, G., Santabárbara, P., Seymour, L., National Cancer Institute of Canada Clinical Trials Group. (2005) Erlotinib in previously treated non-small-cell lung cancer. New England Journal of Medecine, 353, 123-132.
http://dx.doi.org/10.1056/NEJMoa050753
[3] Yamazaki, S., Vicini, P., Shen, Z., Zou, H.Y., Lee, J., Li, Q., Christensen, J.G., Smith, B.J. and Shetty, B. ((2012) Pharmacokinetic/pharmacodynamic modeling of crizotinib for anaplastic lymphoma kinase inhibition and antitumor efficacy in human tumor xenograft mouse models. Journal of Pharmacology and Experimental Therapeutics, 340, 549-557.
http://dx.doi.org/10.1124/jpet.111.188870
[4] Kwak, E.L., Camidge, D.R., Clark, J., Shapiro, G.I., Maki, R.G., Ratain, M.J., Solomon, B., Bang, Y., Ou, S. and Salgia, R. (2009) Clinical activity observed in a Phase I dose escalation trial of an oral c-met and ALK inhibitor, PF-02341066. Journal of Clinical Oncology, 27, Abst. 3509.
[5] Crino, L., Kim, D., Riely, G.J., Janne, P.A., Blackhall, F.H., Camidge, D.R., et al. (2011) Initial Phase II results with crizotinib in advanced ALK-positive non-small cell lung cancer (NSCLC): PROFILE 1005. Journal of Clinical Oncology, 29, Abst. 7514.
[6] Crizotinib [package insert]. (2011)
http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202570s000lbl.pdf
[7] Ding, L., Getz, G., Wheeler, D.A., Mardis, E.R., Mc-Lellan, M.D., Cibulskis, K., et al. (2008) Somatic mutations affect key pathways in lung adenocarcinoma. Nature, 455, 1069-1075.
http://dx.doi.org/10.1038/nature07423
[8] Soda, M., Choi, Y.L., Enomoto, M., Takada, S., Yamashita, Y., Ishikawa, S., Fujiwara, S.-I., Watanabe, H., Kurashina, K., Hatanaka, H., Bando, M., Ohno, S., Ishikawa, Y., Aburatani, H., Niki, T., Sohara, Y., Sugiyama, Y. and Mano, H. (2007) Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature, 448, 561-566. http://dx.doi.org/10.1038/nature05945
[9] Inamura, K., Takeuchi, K., Togashi, Y., Nomura, K., Ninomiya, H., Okui, M., Satoh, Y., Okumura, S., Nakagawa, K., Soda, M., Choi, Y.L., Niki, T., Mano, H. and Ishikawa, Y. (2008) EML4-ALK fusion is linked to histological characteristics in a subset of lung cancers. Journal of Thoracic Oncology, 3, 13-17.
http://dx.doi.org/10.1097/JTO.0b013e31815e8b60
[10] Palmer, R.H., Vernersson, E., Grabbe, C. and Hallberg, B. (2009) Anaplastic lymphoma kinase: Signalling in development and disease. Biochemical Journal, 420, 345.
http://dx.doi.org/10.1042/BJ20090387
[11] Mourali, J., Bénard, A., Lourenco, F.C., Monnet, C., Greenland, C., Moog-Lutz, C., Racaud-Sultan C, Gonzalez-Dunia, D., Vigny, M., Mehlen, P., Delsol, G. and Allouche, M. (2006) Anaplastic lymphomakinase is a dependence receptor whose proapoptotic functions are activated by caspase cleavage. Molecular and Cellular Biology, 26, 6209-6222.
http://dx.doi.org/10.1128/MCB.01515-05
[12] Fallet, V., Toper, C., Antoine, M., Cadranel, J. and Wislez, M. (2012) Crizotinib, modalités pratiques d’un traitement personnalisé. Bulletin de Cancer, 99, 787-791.
[13] Janoueix-Lerosey, I., Lequin, D., Brugières, L., Ribeiro, A., de Pontual, L., Combaret, V., Raynal, V., Puisieux, A., Schleiermacher, G., Pierron, G., Valteau-Couanet, D., Frebourg, T., Michon, J., Lyonnet, S., Amiel, J. and Delattre, O. (2008) Somatic and germline activating mutations of the ALK kinase receptor in neuroblastoma. Nature, 455, 967-970. http://dx.doi.org/10.1038/nature07398
[14] Camidge, D.R. and Doebele, R.C. (2012) Treating ALK-positive lung cancer early successes and future challenges. Nature Reviews Clinical Oncology, 3, 268-277.
http://dx.doi.org/10.1038/nrclinonc.2012.43
[15] Kwak, E.L., Bang, Y.J., Camidge, D.R., Shaw, A.T., Solomon, B., Maki, R.G., Ou, S.H., Dezube, B.J., Jänne, P.A., Costa, D.B., Varella-Garcia, M., Kim, W.H., Lynch, T.J., Fidias, P., Stubbs, H., Engelman, J.A., Sequist, L.V., Tan, W., Gandhi, L., Mino-Kenudson, M,. Wei, G.C., Shreeve, S.M., Ratain, M.J., Settleman, J., Christensen, J.G., Haber, D.A., Wilner, K., Salgia, R., Shapiro, G.I., Clark, J.W. and Iafrate, A.J. (2010) Anaplastic lymphoma kinase inhibition in non-small cell lung cancer. New England Journal of Medecine, 363, 1693-1703.
http://dx.doi.org/10.1056/NEJMoa1006448
[16] Camidge, D.R., Bang, Y.J, Kwak, E.L, Iafrate, A.J., Varella-Garcia, M., Fox, S.B., Riely, G.J., Solomon, B., Ou, S.H., Kim, D.W., Salgia, R., Fidias, P., Engelman, J.A., Gandhi, L., Jänne, P.A., Costa, D.B., Shapiro, G.I., Lorusso, P., Ruffner, K., Stephenson, P., Tang, Y., Wilner, K., Clark, J.W. and Shaw, A.T. (2012) Activity and safety of crizotinib in patients with ALK-positive non-small-cell lung cancer: Updated results from a Phase 1 study. Lancet Oncology, 13, 1011-1019.
http://dx.doi.org/10.1016/S1470-2045(12)70344-3
[17] Shaw, A.T., Kim, D.W., Nakagawa, K., Seto, T., Crinó, L., Ahn, M.J., De Pas, T., Besse, B., Solomon, B.J., Blackhall, F., Wu, Y.L., Thomas, M., O’Byrne, K.J., Moro-Sibilot, D., Camidge, D.R., Mok, T., Hirsh, V., Riely, G.J., Iyer, S., Tassell, V., Polli, A., Wilner, K.D. and Jänne, P.A. (2013) Crizotinib versus chemotherapy in advanced ALKpositive lung cancer. New England Journal of Medecine, 368, 2385-2394.
http://dx.doi.org/10.1056/NEJMoa1214886
[18] Lee, J.O., Kim, T.M., Lee, S.H., Kim, D.W., Kim, S., Jeon, Y.K., Chung, D.H., Kim, W.H., Kim, Y.T., Yang, S.C., Kim, Y.W., Heo, D.S. and Bang, Y.J. (2011) Anaplastic lymphoma kinase translocation: A predictive biomarker of pemetrexed in patients with non-small cell lung cancer. Journal of Thoracic Oncology, 6, 1474-1480.
http://dx.doi.org/10.1097/JTO.0b013e3182208fc2
[19] Ou, S.H., Azada, M., Dy, J. and Stiber, J.A. (2011) Asymptomatic profound sinus bradycardia (heart rate ≤ 45) in non-small cell lung cancer patients treated with crizotinib. Journal of Thoracic Oncology, 6, 2135-2137.
http://dx.doi.org/10.1097/JTO.0b013e3182307e06
[20] Zhang, S., Wang, F., Keats, J., Zhu, X., Ning, Y., Wardwell, S.D., Moran, L., Mohemmad, Q.K., Anjum, R., Wang, Y., Narasimhan, N.I., Dalgarno, D., Shakespeare, W.C., Miret, J.J., Clackson, T. and Rivera, V.M. (2011) Crizotinib-resistant mutants of EML4-ALK identified through an accelerated mutagenesis screen. Chemical Biology and Drug Design, 78, 999-1005.
http://dx.doi.org/10.1111/j.1747-0285.2011.01239.x
[21] Doebele, R.C., Pilling, A.B., Aisner, D.L., Kutateladze, T.G., Le, A.T., Weickhardt, A.J., Kondo, K.L., Linderman, D.J., Heasley, L.E., Franklin, W.A., Varella-Garcia, M. and Camidge, D.R. (2012) Mechanisms of resistance to crizotinib in patients with ALK gene rearranged nonsmall cell lung cancer. Clinical Cancer Research, 18, 1472-1482. http://dx.doi.org/10.1158/1078-0432.CCR-11-2906
[22] Katayama, R., Shaw, A.T., Khan, T.M., Mino-Kenudson, M., Solomon, B.J., Halmos, B., Jessop, N.A., Wain, J.C., Yeo, A.T., Benes, C., Drew, L., Saeh, J.C., Crosby, K., Sequist, L.V., Iafrate, A.J. and Engelman, J.A. (2012) Mechanisms of acquired crizotinib resistance in ALK-rearranged lung cancers. Science Translational Medicine, 4, 120ra17.
[23] Sasaki, T., Koivunen, J., Ogino, A., Yanagita, M., Nikiforow, S., Zheng, W., Lathan, C., Marcoux, J.P., Du, J., Okuda, K., Capelletti, M., Shimamura, T., Ercan, D., Stumpfova, M., Xiao, Y., Weremowicz, S., Butaney, M., Heon, S., Wilner, K., Christensen, J.G., Eck, M.J., Wong, K.K., Lindeman, N., Gray, N.S., Rodig, S.J. and Jänne, P.A. (2011) A novel ALK secondary mutation and EGFR signaling cause resistance to ALK kinase inhibitors. Cancer Research, 71, 6051-6060.
http://dx.doi.org/10.1158/0008-5472.CAN-11-1340

  
comments powered by Disqus

Copyright © 2019 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.