CC BY-NC-ND 4.0 · Indian J Med Paediatr Oncol 2017; 38(01): 15-17
DOI: 10.4103/0971-5851.203502
Original Article

Differential Toxicities of Tyrosine Kinase Inhibitors in the Management of Metastatic Lung Cancer

Karthik S Udupa
Department of Medical Oncology, KMC, Manipal, Karnataka, India
,
Rejiv Rajendranath
Department of Medical Oncology, Cancer Institute, Chennai, Tamil Nadu, India
,
Tenali Sagar
Department of Medical Oncology, Cancer Institute, Chennai, Tamil Nadu, India
,
Joseph Thomas
Department of Medical Oncology, KMC, Manipal, Karnataka, India
› Author Affiliations
Financial support and sponsorship Nil.

Abstract

Introduction: Erlotinib and gefitinib are the most commonly used epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in the treatment of EGFR mutant nonsmall cell lung cancer (NSCLC). Both erlotinib and gefitinib have shown equal efficacy in terms of response rates and overall survival. Hence, their toxicity profile becomes the most important determining factor in choosing these agents when treating EGFR mutant NSCLC. In this study, we compared the toxicity profile of erlotinib and gefitinib among an Indian subset of lung cancer patients. Materials and Methods: In this prospective nonrandomized study, 85 patients of South Indian origin with NSCLC were tested for EGFR mutation status, and EGFR mutant patients were started on either erlotinib or gefitinib. They were periodically monitored for drug toxicities. Results: Out of the 85 patients tested, 34 patients were positive for EGFR mutation. Eleven of them were started on erlotinib and 23 were started on gefitinib. The most common side effect of TKIs was skin rash. Nine out of the 11 patients started on erlotinib and 7 of the 23 patients started on gefitinib had skin rash. Grade 3 and 4 skin rash was significantly more among patients treated with erlotinib which resulted in treatment delays. Other side effects of TKIs such as diarrhea and deranged liver functions were similar among the both subsets of patients. Conclusion: Skin toxicity is the major and serious side effect with erlotinib among Indian patients with EGFR mutant lung cancer. This resulted in significant treatment delay, which might adversely affect the overall survival of patients. Gefitinib was better tolerated and had a safer toxicity profile compared to erlotinib in Indian patients.



Publication History

Article published online:
06 July 2021

© 2017. Indian Society of Medical and Paediatric Oncology. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/.)

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  • References

  • 1 Maemondo M, Inoue A, Kobayashi K, Sugawara S, Oizumi S, Isobe H, et al. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med 2010;362:2380-8.
  • 2 Mitsudomi T, Morita S, Yatabe Y, Negoro S, Okamoto I, Tsurutani J, et al. Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): An open label, randomised phase 3 trial. Lancet Oncol 2010;11:121-8.
  • 3 Zhou C, Wu YL, Chen G, Feng J, Liu XQ, Wang C, et al. Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): A multicentre, open-label, randomised, phase 3 study. Lancet Oncol 2011;12:735-42.
  • 4 Rosell R, Carcereny E, Gervais R, Vergnenegre A, Massuti B, Felip E, et al. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): A multicentre, open-label, randomised phase 3 trial. Lancet Oncol 2012;13:239-46.
  • 5 Wu WS, Chen YM, Tsai CM, Shih JF, Chiu CH, Chou KT, et al. Erlotinib has better efficacy than gefitinib in adenocarcinoma patients without EGFR-activating mutations, but similar efficacy in patients with EGFR-activating mutations. Exp Ther Med 2012;3:207-13.
  • 6 Lee E, Keam B, Kim DW, Kim TM, Lee SH, Chung DH, et al. Erlotinib versus gefitinib for control of leptomeningeal carcinomatosis in non-small-cell lung cancer. J Thorac Oncol 2013;8:1069-74.
  • 7 National Institutes of Health. National Cancer Institute. Common Terminology Criteria for Adverse Events (CTCAE); Version 4.0 Published: May 28, 2009 (v4.03: June 14, 2010). 2010. Available from: http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_5x7.pdf. [Last accessed on 2016 Jun 7].
  • 8 Li J, Karlsson MO, Brahmer J, Spitz A, Zhao M, Hidalgo M, et al. CYP3A phenotyping approach to predict systemic exposure to EGFR tyrosine kinase inhibitors. J Natl Cancer Inst 2006;98:1714-23.
  • 9 Tan AR, Yang X, Hewitt SM, Berman A, Lepper ER, Sparreboom A, et al. Evaluation of biologic end points and pharmacokinetics in patients with metastatic breast cancer after treatment with erlotinib, an epidermal growth factor receptor tyrosine kinase inhibitor. J Clin Oncol 2004;22:3080-90.