Efficacy of first-line erlotinib in non-small cell lung cancer patients undergoing dose reduction and those with a low body surface area: A population-based observational study by the Ibaraki Thoracic Integrative (POSITIVE) Research Group

Inagaki,Masaharu; Shinohara,Yoko; Kaburagi,Takayuki; Homma,Shinsuke; Hizawa,Nobuyuki; Nakamura,Hiroyuki; Hayashihara,Kenji; Saito,Takefumi; Ishikawa,Hiroichi; Ichimura,Hideo; Nawa,Takeshi; Kikuchi,Norihiro; Miyazaki,Kunihiko; Kodama,Takahide; Kamiyama,Koichi; Satoh,Hiroaki; Furukawa,Kinya

doi:10.3892/mco.2015.720

March-2016 Volume 4 Issue 3

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March-2016 Volume 4 Issue 3

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Article

Efficacy of first-line erlotinib in non-small cell lung cancer patients undergoing dose reduction and those with a low body surface area: A population-based observational study by the Ibaraki Thoracic Integrative (POSITIVE) Research Group

Authors:
- Masaharu Inagaki
- Yoko Shinohara
- Takayuki Kaburagi
- Shinsuke Homma
- Nobuyuki Hizawa
- Hiroyuki Nakamura
- Kenji Hayashihara
- Takefumi Saito
- Hiroichi Ishikawa
- Hideo Ichimura
- Takeshi Nawa
- Norihiro Kikuchi
- Kunihiko Miyazaki
- Takahide Kodama
- Koichi Kamiyama
- Hiroaki Satoh
- Kinya Furukawa
View Affiliations / Copyright

Affiliations: Divisions of Thoracic Surgery and Respiratory Medicine, Tsuchiura Kyodo General Hospital and Regional Cancer Center, Tsuchiura, Ibaraki 300‑0053, Japan, Division of Respiratory Medicine, Ibaraki Prefectural Central Hospital and Regional Cancer Center, Kasama, Ibaraki 309‑1793, Japan, Division of Respiratory Medicine, Faculty of Clinical Medicine, University of Tsukuba, Tsukuba, Ibaraki 305‑8576, Japan, Divisions of Thoracic Surgery and Respiratory Medicine, Tokyo Medical University, Ibaraki Medical Center Hospital, Ami, Ibaraki 300‑0395, Japan, Division of Respiratory Medicine, Ibaraki Higashi National Hospital, Tokai, Ibaraki 319‑1113, Japan, Division of Respiratory Medicine, Tsukuba Medical Center Hospital and Regional Cancer Center, Tsukuba, Ibaraki 305‑8558, Japan, Divisions of Thoracic Surgery and Respiratory Medicine, Hitachi General Hospital, Hitachi, Ibaraki 317‑0077, Japan, Division of Respiratory Medicine, Kasumigaura Medical Center, Tsuchiura, Ibaraki 300‑0812, Japan, Division of Respiratory Medicine, Ryugasaki Saiseikai General Hospital, Ryugasaki, Ibaraki 301‑0854, Japan, Division of Thoracic Surgery, Tsukuba Kinen General Hospital, Tsukuba, Ibaraki 300‑2622, Japan, Division of Respiratory Medicine, Mito Medical Center, Institute of Clinical Medicine, University of Tsukuba, Mito, Ibaraki 310‑0015, Japan
Pages: 425-428
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Published online on: December 21, 2015

https://doi.org/10.3892/mco.2015.720
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Abstract

The aim of the present study was to evaluate the efficacy of erlotinib, one of the epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR‑TKIs), in patients undergoing dose reduction and in those with a low body surface area (BSA). The association between dose reduction, low BSA and efficacy, including response rate, disease control rate, time to treatment failure and overall survival, were evaluated in patients prescribed first‑line erlotinib for EGFR mutated non‑small cell lung cancer patients between April 2012 and March 2015. A total of 22 patients received first‑line erlotinib during the study period. A dose reduction of erlotinib for the reason of low BSA and poor performance status occurred in 14 (63.6%) of the patients: 6 (27.3%) had initial dose reduction, 6 (27.3%) had dose reduction in their clinical courses, and 2 (9.1%) had both. Dose reduction of erlotinib with the initial dose of erlotinib/BSA was >80 mg/m2, and longest‑term prescribed dose of erlotinib/BSA was >50 mg/m2, which may have no association with a survival disadvantage. Dose‑reduction estimation studies for TKIs may be crucial, particularly for patients with a low BSA. Future prospective studies and confirmation of these results in population‑based retrospective ones investigating the incidence of dose reduction in patients with AEs and those with low BSA may be required for the efficient use of erlotinib in common clinical practice.

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1	Seymour L and Eisenhauer E: A review of dose-limiting events in phase I trials: Antimetabolites show unpredictable relationships between dose and toxicity. Cancer Chemother Pharmacol. 47:2–10. 2001. View Article : Google Scholar : PubMed/NCBI
2	Hoekstra R, Verweij J and Eskens FA: Clinical trial design for target specific anticancer agents. Invest New Drugs. 21:243–250. 2003. View Article : Google Scholar : PubMed/NCBI
3	Zohar S, Lian Q, Levy V, Cheung K, Ivanova A and Chevret S: Quality assessment of phase I dose-finding cancer trials: Proposal of a checklist. Clin Trials. 5:478–485. 2008. View Article : Google Scholar : PubMed/NCBI
4	Wolf M, Swaisland H and Averbuch S: Development of the novel biologically targeted anticancer agent gefitinib: Determining the optimum dose for clinical efficacy. Clin Cancer Res. 10:4607–4613. 2004. View Article : Google Scholar : PubMed/NCBI
5	Takimoto CH: Maximum tolerated dose: Clinical endpoint for a bygone era? Target Oncol. 4:143–147. 2009. View Article : Google Scholar : PubMed/NCBI
6	Yamamoto N, Horiike A, Fujisaka Y, Murakami H, Shimoyama T, Yamada Y and Tamura T: Phase I dose-finding and pharmacokinetic study of the oral epidermal growth factor receptor tyrosine kinase inhibitor Ro50-8231 (erlotinib) in Japanese patients with solid tumors. Cancer Chemother Pharmacol. 61:489–496. 2008. View Article : Google Scholar : PubMed/NCBI
7	Boyer M, Horwood K, Pavlakis N, De Souza P, Millward M, Stein B, Johnston M, Abell F and Rischin D: Efficacy of erlotinib in patients with advanced non-small-cell lung cancer (NSCLC): Analysis of the Australian subpopulation of the TRUST study. Asia Pac J Clin Oncol. 8:248–254. 2012. View Article : Google Scholar : PubMed/NCBI
8	Gahr S, Stoehr R, Geissinger E, Ficker JH, Brueckl WM, Gschwendtner A, Gattenloehner S, Fuchs FS, Schulz C, Rieker RJ, et al: EGFR mutational status in a large series of Caucasian European NSCLC patients: Data from daily practice. Br J Cancer. 109:1821–1828. 2013. View Article : Google Scholar : PubMed/NCBI
9	Kaburagi T, Satoh H, Hayashihara K, Endo T, Hizawa N, Kurishima K, Nishimura Y, Hashimoto T, Nakamura H, Kishi K, et al: Observational study on the efficacy and safety of erlotinib in patients with non-small cell lung cancer. Oncol Lett. 5:435–439. 2013.PubMed/NCBI
10	Ichihara E, Hotta K, Takigawa N, Kudo K, Kato Y, Honda Y, Hayakawa H, Minami D, Sato A, Tabata M, et al: Impact of physical size on gefitinib efficacy in patients with non-small cell lung cancer harboring EGFR mutations. Lung Cancer. 81:435–439. 2013. View Article : Google Scholar : PubMed/NCBI
11	Sato S, Kurishima K, Miyazaki K, Kodama T, Ishikawa H, Kagohashi K, Tamura T, Homma S, Satoh H and Hizawa N: 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. 2:604–608. 2014.PubMed/NCBI
12	Travis WD, Brambilla E, Muller-Hermelink HK and Harris CC: Pathology and Genetics: Tumours of the Lung, Pleura, Thymus and Heart. Lyon: IARC Press. 2004. View Article : Google Scholar
13	Cancer Therapy Evaluation Program, Common Toxicity Criteria for Adverse Events. Version 3.0. http://ctep.cancer.govAccessed. May 15–2014
14	Pennell NA: Integration of EGFR inhibitors and conventional chemotherapy in the treatment of non-small-cell lung cancer. Clin Lung Cancer. 12:350–359. 2011. View Article : Google Scholar : PubMed/NCBI
15	Roengvoraphoj M, Tsongalis GJ, Dragnev KH and Rigas JR: 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. 39:839–850. 2013. View Article : Google Scholar : PubMed/NCBI
16	Hayashibara K, Satoh H, Shinohara Y, Inagaki M, Kaburagi T, Hashimoto T, Kurishima K, Ishikawa H, Ichimura H, Nawa T, et al: A population-based study of gefitinib in patients with non-small cell lung cancer. Med Oncol. 26:222–227. 2009. View Article : Google Scholar : PubMed/NCBI
17	Miles DW, Chan A, Dirix LY, Cortés J, Pivot X, Tomczak P, Delozier T, Sohn JH, Provencher L, Puglisi F, et al: 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. 28:3239–3247. 2010. View Article : Google Scholar : PubMed/NCBI
18	Wittenburg LA and Gustafson DL: Optimizing preclinical study design in oncology research. Chem Biol Interact. 190:73–78. 2011. View Article : Google Scholar : PubMed/NCBI
19	Fujita KI and Sasaki Y: Optimization of cancer chemotherapy on the basis of pharmacokinetics and pharmacodynamics: From patients enrolled in ‘clinical trials’ to those in the ‘real world’. Drug Metab Pharmacokinet. 29:20–28. 2014. View Article : Google Scholar : PubMed/NCBI
20	Fukudo M, Ikemi Y, Togashi Y, Masago K, Kim YH, Mio T, Terada T, Teramukai S, Mishima M, Inui K and Katsura T: Population pharmacokinetics/pharmacodynamics of erlotinib and pharmacogenomic analysis of plasma and cerebrospinal fluid drug concentrations in Japanese patients with non-small cell lung cancer. Clin Pharmacokinet. 52:593–609. 2013. View Article : Google Scholar : PubMed/NCBI
21	Ranson M and Wardell S: Gefitinib, a novel, orally administered agent for the treatment of cancer. J Clin Pharm Ther. 29:95–103. 2004. View Article : Google Scholar : PubMed/NCBI

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Efficacy of first-line erlotinib in non-small cell lung cancer patients undergoing dose reduction and those with a low body surface area: A population-based observational study by the Ibaraki Thoracic Integrative (POSITIVE) Research Group

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