Vol 12, No 4 (2016)
Review paper
Published online: 2016-12-22
Side effects of tyrosine kinase inhibitors — management guidelines
DOI: 10.5603/OCP.2016.0004
Oncol Clin Pract 2016;12(4):113-118.
Abstract
Tyrosine kinase inhibitors (TKI) are molecular targeted therapies that inhibit EGFR-related signal transduction pathway. Non-small cell lung cancer patients harbouring activating mutation benefit more from EGFR TKI in first line treatment than from standard platinum-based chemotherapy in terms of objective response rate, quality of life, progression free survival and, in some cases, overall survival. Treatment-related adverse events are observed in 70 per cent of patients but mainly in mild or moderate grade. The most common adverse events are: skin disorders, fatigue, diarrhoea, and elevated liver enzymes. Rare cases of interstitial lung disease are also observed. In clinical practice the treatment plan is achieved and drug discontinuation is rarely needed provided that the guidelines of prevention and management of the toxicities are followed.
Keywords: tyrosine kinase inhibitorsadverse eventstoxicitymanagement
References
- Costa C, Molina MA, Drozdowskyj A, et al. The impact of EGFR T790M mutations and BIM mRNA expression on outcome in patients with EGFR-mutant NSCLC treated with erlotinib or chemotherapy in the randomized phase III EURTAC trial. Clin Cancer Res. 2014; 20(7): 2001–2010.
- Mok T, Wu YL, Thongprasert S, et al. Gefitinib or Carboplatin–Paclitaxel in Pulmonary Adenocarcinoma. New England Journal of Medicine. 2009; 361(10): 947–957.
- Rosell R, Carcereny E, Gervais R, et al. Spanish Lung Cancer Group in collaboration with Groupe Français de Pneumo-Cancérologie and Associazione Italiana Oncologia Toracica. 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(3): 239–246.
- Yang JCH, Reguart N, Barinoff J, et al. Diarrhea associated with afatinib: an oral ErbB family blocker. Expert Rev Anticancer Ther. 2013; 13(6): 729–736.
- Lacouture ME, Wu S, Robert C, et al. Evolving strategies for the management of hand-foot skin reaction associated with the multitargeted kinase inhibitors sorafenib and sunitinib. Oncologist. 2008; 13(9): 1001–1011.
- Hirsh V. Managing treatment-related adverse events associated with egfr tyrosine kinase inhibitors in advanced non-small-cell lung cancer. Curr Oncol. 2011; 18(3): 126–138.
- Harandi A, Zaidi AS, Stocker AM, et al. Clinical Efficacy and Toxicity of Anti-EGFR Therapy in Common Cancers. J Oncol. 2009; 2009: 567486.
- National Cancer Institute. Common Terminology Criteria for Adverse Events (CTCAE) 04.03.2010.
- Ocvirk J, Heeger S, McCloud P, et al. A review of the treatment options for skin rash induced by EGFR-targeted therapies: Evidence from randomized clinical trials and a meta-analysis. Radiol Oncol. 2013; 47(2): 166–175.
- Soria JC, Felip E, Cobo M, et al. LUX-Lung 8 Investigators. Afatinib versus erlotinib as second-line treatment of patients with advanced squamous cell carcinoma of the lung (LUX-Lung 8): an open-label randomised controlled phase 3 trial. Lancet Oncol. 2015; 16(8): 897–907.
- Ramalingam SS, Jänne PA, Mok T, et al. Dacomitinib versus erlotinib in patients with advanced-stage, previously treated non-small-cell lung cancer (ARCHER 1009): a randomised, double-blind, phase 3 trial. Lancet Oncol. 2014; 15(12): 1369–1378.
- Park K, Tan EH, O'Byrne K, et al. Afatinib versus gefitinib as first-line treatment of patients with EGFR mutation-positive non-small-cell lung cancer (LUX-Lung 7): a phase 2B, open-label, randomised controlled trial. Lancet Oncol. 2016; 17(5): 577–589.
- Takeda M, Okamoto I, Nakagawa K. Pooled safety analysis of EGFR-TKI treatment for EGFR mutation-positive non-small cell lung cancer. Lung Cancer. 2015; 88(1): 74–79.
- Chen X, Pan Y, Zhang S, et al. Rechallenge with gefitinib following severe drug-induced hepatotoxicity in a patient with advanced non-small cell lung cancer: A case report and literature review. Oncol Lett. 2014; 7(3): 878–880.
- Togashi Y, Masago K, Fujita S, et al. Differences in adverse events between 250 mg daily gefitinib and 150 mg daily erlotinib in Japanese patients with non-small cell lung cancer. Lung Cancer. 2011; 74(1): 98–102.
- Shi L, Tang J, Tong Li, et al. Risk of interstitial lung disease with gefitinib and erlotinib in advanced non-small cell lung cancer: a systematic review and meta-analysis of clinical trials. Lung Cancer. 2014; 83(2): 231–239.
- Camus P, Kudoh S, Ebina M. Interstitial lung disease associated with drug therapy. Br J Cancer. 2004; 91 Suppl 2: S18–S23.
- Kowalski DM, Płużański A. Odległe następstwa przeciwnowotworowego leczenia. In: Krzakowski M, Potemski P, Warzocha K, Wysocki P. ed. Onkologia kliniczna. Tom I. Via Medica, Gdańsk 2014: 351–352.
- Żołnierek J. Uzupełnienia. In: Krzakowski M, Potemski P, Warzocha K, Wysocki P. ed. Onkologia kliniczna. Tom I. Via Medica, Gdańsk 2014: 447.
- Cleverley JR, Screaton NJ, Hiorns MP, et al. Drug-induced lung disease: high-resolution CT and histological findings. Clin Radiol. 2002; 57(4): 292–299.
- Kudoh S, Kato H, Nishiwaki Y, et al. Japan Thoracic Radiology Group. Interstitial lung disease in Japanese patients with lung cancer: a cohort and nested case-control study. Am J Respir Crit Care Med. 2008; 177(12): 1348–1357.
- Kuo LC, Lin PC, Wang KF, et al. Successful treatment of gefitinib-induced acute interstitial pneumonitis with high-dose corticosteroid: a case report and literature review. Med Oncol. 2011; 28(1): 79–82.
- Schuler M, Wu YL, Hirsh V, et al. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol. 2013; 31(27): 3327–3334.
- Zhou C, Wu YL, Chen G, 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(8): 735–742.
- Mitsudomi T, Morita S, Yatabe Y, et al. West Japan Oncology Group. 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(2): 121–128.
- Wu YL, Zhou C, Hu CP, et al. Afatinib versus cisplatin plus gemcitabine for first-line treatment of Asian patients with advanced non-small-cell lung cancer harbouring EGFR mutations (LUX-Lung 6): an open-label, randomised phase 3 trial. Lancet Oncol. 2014; 15(2): 213–222.