Disease flare after gefitinib discontinuation.
BACKGROUND
A recent retrospective analysis found that 23% of non-small cell lung cancer patients who acquired resistance to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) demonstrated "disease flare" after discontinuation of EGFR-TKIs. However, limitations of this study present the need for further investigation to elucidate this phenomenon in more detail.


METHODS
We reviewed the clinical records of EGFR mutated patients with advanced lung adenocarcinoma who were treated with gefitinib monotherapy in our hospital between January 2007 and December 2010. Disease flare was defined as unexpected interventions (e.g. radiation therapy or pleural drainage), hospitalization, or death attributable to disease progression after gefitinib discontinuation.


RESULTS
Among 52 eligible patients, only two experienced disease flare (4%; 95% confidence interval: 1-13%). In both cases, interval time from gefitinib discontinuation to disease flare was 11 days, and the brain was the site of flare. Survival time after gefitinib was significantly shorter in the flare patients (78 and 97 days, respectively) compared with the no-flare patients (median 388 days).


CONCLUSIONS
Our analysis demonstrated a lower incidence rate of disease flare after gefitinib discontinuation compared with the previous report, but the prognosis was similarly poor.
Division of Thoracic Oncology, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho Sunto-gun, Shizuoka 411-8777, Japan; Third Department of Internal Medicine, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-8509, Japan. Electronic address: h-akamat@wakayama-med.ac.jp.
Hiroaki
H
Akamatsu
Division of Thoracic Oncology, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho Sunto-gun, Shizuoka 411-8777, Japan. Electronic address: a.ono@scchr.jp.
Akira
A
Ono
Division of Thoracic Oncology, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho Sunto-gun, Shizuoka 411-8777, Japan; Department of Respiratory Medicine, Juntendo University, School of Medicine, 2-1-1 Hongou, Bunkyou-ku, Tokyo 113-8421, Japan. Electronic address: tshukuya@juntendo.ac.jp.
Takehito
T
Shukuya
Division of Thoracic Oncology, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho Sunto-gun, Shizuoka 411-8777, Japan; Department of Clinical Oncology, Osaka City General Hospital, 2-13-22 Miyakojimahondohri, Miyakojima-ku, Osaka 534-0021, Japan. Electronic address: a-tsuya@hospital.city.osaka.jp.
Asuka
A
Tsuya
Division of Thoracic Oncology, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho Sunto-gun, Shizuoka 411-8777, Japan; Department of Respiratory Medicine, Yokohama Munincipal Citizen׳s Hospital, 56 Okazawa-cho, Hodogaya-ku, Yokohama, Kanagawa 240-8555, Japan. Electronic address: yu43-nakamura@city.yokohama.jp.
Yukiko
Y
Nakamura
Division of Thoracic Oncology, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho Sunto-gun, Shizuoka 411-8777, Japan. Electronic address: h.kenmotsu@scchr.jp.
Hirotsugu
H
Kenmotsu
Division of Thoracic Oncology, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho Sunto-gun, Shizuoka 411-8777, Japan. Electronic address: t.naito@scchr.jp.
Tateaki
T
Naito
Division of Thoracic Oncology, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho Sunto-gun, Shizuoka 411-8777, Japan. Electronic address: ha.murakami@scchr.jp.
Haruyasu
H
Murakami
Division of Diagnostic Radiology, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho Sunto-gun, Shizuoka 411-8777, Japan. Electronic address: m.endo@scchr.jp.
Masahiro
M
Endo
Division of Radiation Oncology, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho Sunto-gun, Shizuoka 411-8777, Japan. Electronic address: t.nakajima@scchr.jp.
Takashi
T
Nakajima
Division of Thoracic Oncology, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho Sunto-gun, Shizuoka 411-8777, Japan; Third Department of Internal Medicine, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-8509, Japan. Electronic address: nb.yamamo@wakayama-med.ac.jp.
Nobuyuki
N
Yamamoto
Division of Thoracic Oncology, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho Sunto-gun, Shizuoka 411-8777, Japan. Electronic address: t.takahashi@scchr.jp.
Toshiaki
T
Takahashi
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D018450:Disease Progression; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011799:Quinazolines / Q000627:therapeutic use*; D012189:Retrospective Studies; D028761:Withholding Treatment
D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; C512478:EGFR protein, human; D066246:ErbB Receptors; D000077156:Gefitinib
Disease flare; EGFR-tyrosine kinase inhibitor (EGFR-TKI); Epidermal growth factor receptor (EGFR) mutation; Gefitinib