DOI QR코드

DOI QR Code

Low-dose Epidermal Growth Factor Receptor (EGFR)-Tyrosine Kinase Inhibition of EGFR Mutation-positive Lung Cancer: Therapeutic Benefits and Associations Between Dosage, Efficacy and Body Surface Area

  • Hirano, Ryosuke (Department of Respiratory Medicine, Fukuoka University School of Medicine) ;
  • Uchino, Junji (Department of Respiratory Medicine, Fukuoka University School of Medicine) ;
  • Ueno, Miho (Department of Pharmacy, Fukuoka University Hospital) ;
  • Fujita, Masaki (Department of Respiratory Medicine, Fukuoka University School of Medicine) ;
  • Watanabe, Kentaro (Department of Respiratory Medicine, Fukuoka University School of Medicine)
  • Published : 2016.03.07

Abstract

A key drug for treatment of EGFR mutation-positive non-small cell lung cancer is epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). While the dosage of many general anti-tumor drugs is adjusted according to the patient body surface area, one uniform dose of most TKIs is recommended regardless of body size. In many cases, dose reduction or drug cessation is necessary due to adverse effects. Disease control, however, is frequently still effective, even after dose reduction. In this study, we retrospectively reviewed the characteristics of 26 patients at Fukuoka University Hospital between January 2004 and January 2015 in whom the EGFR-TKI dose was reduced with respect to progression free survival and overall survival. There were 10 and 16 patients in the gefitinib group and the erlotinib group, respectively. The median progression-free survival in the gefitinib group and the erlotinib group was 22.4 months and 14.1 months, respectively, and the median overall survival was 30.5 months and 32.4 months, respectively. After stratification of patients by body surface area, the overall median progression-free survival was significantly more prolonged in the low body surface area (<1.45 m2) group (25.6 months) compared to the high body surface area (>1.45 m2) group (9.7 months) (p=0.0131). These results indicate that low-dose EGFR-TKI may sufficiently control disease without side effects in lung cancer patients with a small body size.

Keywords

References

  1. Dubois D, Dubois EF (1989). Nutrition metabolism classic - a formula to estimate the approximate surface-area if height and weight be known (reprinted from archives internal medicine, Vol 17, Pg 863, 1916). Nutrition, 5, 303-11.
  2. Fukuoka M, Yano S, Giaccone G, et al (2003). Multi-institutional randomized phase II trial of gefitinib for previously treated patients with advanced non-small-cell lung cancer (The IDEAL 1 Trial) [corrected]. J Clin Oncol, 21, 2237-46. https://doi.org/10.1200/JCO.2003.10.038
  3. Ichihara E, Hotta K, Takigawa N, et al (2013). Impact of physical size on gefitinib efficacy in patients with non-small cell lung cancer harboring EGFR mutations. Lung Cancer, 81, 435-9. https://doi.org/10.1016/j.lungcan.2013.05.021
  4. Kawaguchi T, Hamada A, Hirayama C, et al (2009). Relationship between an effective dose of imatinib, body surface area, and trough drug levels in patients with chronic myeloid leukemia. Int J Hematol, 89, 642-8. https://doi.org/10.1007/s12185-009-0315-4
  5. Kris MG, Natale RB, Herbst RS, et al (2003). Efficacy of gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, in symptomatic patients with non-small cell lung cancer: a randomized trial. JAMA, 290, 2149-58. https://doi.org/10.1001/jama.290.16.2149
  6. Kudo K, Hotta K, Ichihara E, et al (2015). Impact of body surface area on survival in EGFR-mutant non-small cell lung cancer patients treated with gefitinib monotherapy: observational study of the Okayama Lung Cancer Study Group 0703. Cancer Chemother Pharmacol, 76, 251-6. https://doi.org/10.1007/s00280-015-2789-5
  7. Maemondo M, Inoue A, Kobayashi K, et al (2010). Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med, 362, 2380-8. https://doi.org/10.1056/NEJMoa0909530
  8. Miles DW, Chan A, Dirix LY, et al (2010). Phase III study of bevacizumab plus docetaxel compared with placebo plus docetaxel for the first-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol, 28, 3239-47. https://doi.org/10.1200/JCO.2008.21.6457
  9. Mitsudomi T, Morita S, Yatabe Y, et al (2010). 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, 11, 121-8. https://doi.org/10.1016/S1470-2045(09)70364-X
  10. Nakagawa K, Tamura T, Negoro S, et al (2003). Phase I pharmacokinetic trial of the selective oral epidermal growth factor receptor tyrosine kinase inhibitor gefitinib ('Iressa', ZD1839) in Japanese patients with solid malignant tumors. Ann Oncol, 14, 922-30. https://doi.org/10.1093/annonc/mdg250
  11. Roengvoraphoj M, Tsongalis GJ, Dragnev KH, et al (2013). Epidermal growth factor receptor tyrosine kinase inhibitors as initial therapy for non-small cell lung cancer: focus on epidermal growth factor receptor mutation testing and mutation-positive patients. Cancer Treat Rev, 39, 839-50. https://doi.org/10.1016/j.ctrv.2013.05.001
  12. Rosell R, Carcereny E, Gervais R, et al (2012). Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-smallcell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol, 13, 239-46. https://doi.org/10.1016/S1470-2045(11)70393-X
  13. Sato S, Kurishima K, Miyazaki K, et al (2014). Efficacy of tyrosine kinase inhibitors in non-small-cell lung cancer patients undergoing dose reduction and those with a low body surface area. Mol Clin Oncol, 2, 604-8. https://doi.org/10.3892/mco.2014.281
  14. Satoh H, Inoue A, Kobayashi K, et al (2011). Low-dose gefitinib treatment for patients with advanced non-small cell lung cancer harboring sensitive epidermal growth factor receptor mutations. J Thorac Oncol, 6, 1413-7. https://doi.org/10.1097/JTO.0b013e31821d43a8
  15. Seto T, Kato T, Nishio M, et al (2014). Erlotinib alone or with bevacizumab as first-line therapy in patients with advanced non-squamous non-small-cell lung cancer harbouring EGFR mutations (JO25567): an open-label, randomised, multicentre, phase 2 study. Lancet Oncol, 15, 1236-44. https://doi.org/10.1016/S1470-2045(14)70381-X
  16. Siegel R, Ma J, Zou Z, et al (2014). Cancer statistics, 2014. CA Cancer J Clin, 64, 9-29. https://doi.org/10.3322/caac.21208
  17. Yeo WL, Riely GJ, Yeap BY, et al (2010). Erlotinib at a dose of 25 mg daily for non-small cell lung cancers with EGFR mutations. J Thorac Oncol, 5, 1048-53. https://doi.org/10.1097/JTO.0b013e3181dd1386
  18. Yoshioka H, Hotta K, Kiura K, et al (2010). A phase II trial of erlotinib monotherapy in pretreated patients with advanced non-small cell lung cancer who do not possess active EGFR mutations: Okayama Lung Cancer Study Group trial 0705. J Thorac Oncol, 5, 99-104. https://doi.org/10.1097/JTO.0b013e3181c20063
  19. Zhou C, Wu YL, Chen G, et al (2011). Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, openlabel, randomised, phase 3 study. Lancet Oncol, 12, 735-42. https://doi.org/10.1016/S1470-2045(11)70184-X

Cited by

  1. Comparison of gefitinib, erlotinib and afatinib in non-small cell lung cancer: A meta-analysis vol.140, pp.12, 2017, https://doi.org/10.1002/ijc.30691
  2. Gefitinib provides similar effectiveness and improved safety than erlotinib for east Asian populations with advanced non–small cell lung cancer: a meta-analysis vol.18, pp.1, 2018, https://doi.org/10.1186/s12885-018-4685-y
  3. Gefitinib provides similar effectiveness and improved safety than erlotinib for advanced non-small cell lung cancer vol.97, pp.16, 2018, https://doi.org/10.1097/MD.0000000000010460