Download The efficacy and safety of lcotinib in patients with advanced non

Int J Clin Exp Med 2016;9(9):18360-18366
www.ijcem.com /ISSN:1940-5901/IJCEM0028938
Original Article
The efficacy and safety of lcotinib
in patients with advanced non-small
cell lung cancer: compare with gefitinib
Zhe Zhang1, Qiming Wang1, Hong Tang1, Suhua Xia2, Zelai He3, Zhen He1, Lili Wang1, Hui Zhu1, Shaomei Li1,
Yufeng Wu1
Department of Internal Medicine, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital,
Zhengzhou 450008, Henan, PR China; 2Suzhou University, Suzhou 215000, Jiangsu, PR China; 3The 2nd Affiliated
Hospital & Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang, PR China
1
Received March 23, 2016; Accepted August 14, 2016; Epub September 15, 2016; Published September 30, 2016
Abstract: Background: As is known to all, non-small-cell lung cancer (NSCLC) is one of the most lethal malignancies
with few effective treatment modalities. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are
very effective for treating the patients with EGFR mutations. As the first homegrown anticancer drug, icotinib is a
novel, orally administered, and reversible EGFR-TKI. This study aimed to compare the efficacy and safety of icotinib
with gefitinib to patients with advanced NSCLC. Methods: The retrospective analysis included 219 patients with
stage IIIB/IV NSCLC harbouring mutant-type EGFR. The selected patients received either icotinib (125 mg thrice
daily, n=126) or gefitinib (250 mg daily, n=93) orally until the disease progression or unacceptable toxicities appeared. Meanwhile, side effects, tumor responses, progression-free survival (PFS) and overall survival time (OS)
were recorded for analysis. Results: Compared with gefitinib, it was observed that the overall objective response
rate of patients was 46.0% and the disease control rate was 86.5%. The life quality of patients was improved accordingly. The main toxicities of icotinib were skin toxicity (rash) and diarrhea. A total of 4 patients were found with
moderate adverse reactions, which was lower than gefitinib. The median PFS was 6.5 months in the icotinib group
and 6.3 months in the gefitinib group, and the OS was 20.9 months in the icotinib group and 20.3 months in the gefitinib group. Conclusion: Associated with a lower number of treatment-related adverse cases than gefitinib, icotinib
was not inferior to gefitinib in treating advanced NSCLC. In conclusion, China’s homemade EGFR-TKI, icotinib has
provided a new choice for NSCLC patients.
Keywords: NSCLC, EGFR-TKIs, icotinib, gefitinib, adverse reactions
Introduction
Featured with better efficacy and lighter
adverse reactions, epidermal growth factor
receptor tyrosine kinase inhibitors (EGFR-TKIs)
have been increasingly applied as maintenance
therapy for patients with advanced non-smallcell lung cancer (NSCLC) [1, 2]. EGFR mutations
are more common in Asian people (40-50%)
than European (10%), especially in a subset of
patients like non-smoking Asian women with
adenocarcinoma [3]. Therefore, EGFR-TKIs,
such as gefitinib and erlotinib, is particularly
beneficial for Asian population [4, 5]. As the
first homegrown EGFR-TKI drug designed, synthesized, and screened by Zhejiang Beida
Pharmaceutical Co. Ltd (Zhejiang, China), icotinib is with independent intellectual property
rights [6]. Although the full pharmacokinetic
parameter profiles of icotinib have been published [7], further studies are needed to investigate the efficacy and safety of icotinib compared with other EGFR-TKIs like gefitinib. In current study, by analyzing the data of patients
with advanced NSCLC who were treated in
Henan Cancer Hospital from June 2011 to
November 2014, this study evaluated the efficacy and safety of icotinib in patients with
advanced NSCLC. Therefore, this study can be
of important reference for further clinical
medication.
The efficacy and safety of icotinib in patients with non-small cell lung cancer
Patients and methods
Patients
The selected patients had histologically confirmed as stage IIIB or stage IV with the
American Joint Committee on Cancer [AJCC]
6th edition of tumor-node-metastasis [TNM]
staging system. Moreover, they were diagnosed
with NSCLC accompanying with EGFR-mutant,
and their disease progression was at least one
period of platinum-based chemotherapy. Other
selection criteria included: age from 18 to 75;
Eastern Cooperative Oncology Group (ECOG);
performance status (PS) 0-2; at least one measurable lesion by the Response Evaluation
Criteria in Solid Tumors version 1.1 (RECIST
1.1); adequate hematologic and biochemical
values; and without receiving other antineoplastic therapy during the application of icotinib
or gefitinib treatment. In addition, patients
would be excluded if they received any previous
human EGFR-TKIs or other molecular target
drugs or if they had serious or severe hypersensitivity reactions to icotinib hydrochloride or any
of its excipients. Other excluded criteria contain: symptomatic brain metastases; malignant
tumor within the last five years; severe infection; congestive heart failure; previous treatment with drugs targeting EGFR; and a history
of interstitial lung disease.
RECIST 1.1, the tumor response assessment
was divided into complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), while the objective response
rate (ORR) was defined as the sum of CR and
PR, and the disease control rate (DCR) was
defined as the sum of CR, PR and SD.
Meanwhile, the toxic effects were monitored
and graded based on the National Cancer
Institute Common Toxicity Criteria for Adverse
Events version 3.0 (CTCAE 3.0).
Statistical analysis
The analysis of this study was performed by
SPSS version 17.0 software (SPSS Inc., Chicago,
IL, USA). The safety and toxicity was analyzed
with a descriptive statistical method in the
safety set. Frequency and percentage were
used to describe the categorical data. The
mean, standard deviation, median, minimum
and maximum were utilized to illustrate the
measurement data. Besides, χ2 test was applied to compare the total incidence and the
major adverse events between different groups. The Kaplan-Meier curve was performed to
estimate the median for PFS and OS and draw
the survival curves. The threshold of P<0.05
was defined as statistically significant.
Results
Methods
Demographic data
Patients in icotinib group received 125 mg oral
icotinib in tablet form three times per day while
those in gefitinib group received 250 mg gefitinib in tablet form once daily, until they reach
the required disease progression or unacceptable toxicity. Side effects and tumor response
of the treatment were observed, including clinical symptoms, progression-free survival (PFS)
and overall survival time (OS).
Between June 2011 and November 2014, a
total of 128 patients were enrolled in icotinib
group, in which 126 were evaluated for the efficacy and safety analysis (while 2 cases failed
to complete the experiment due to severe
adverse reactions). A total of 93 patients were
in Gefitinib group. Compared with the demographic situation of patients in two groups, the
chi-square test indicated that there was no significant difference in gender, age, ECOG PS,
smoking history, BMI, pathological typing and
clinical staging of the two groups (P>0.05). The
specific information of two groups was shown
in Table 1.
Response evaluation
Every enrolled patient must include symptom
evaluation one week before enrollment and
four weeks after receiving icotinib or gefitinib.
The detailed evaluation criteria included ECOG
PS, eating and sleeping, choking sensation in
chest, pectoralgia, coughing, breathing difficulties, blood in sputum and other symptoms, as
well as rash, diarrhea, fatigue, lack of appetite,
nausea and other side effects. According to
18361
Symptom and quality of life (QoL)
This study evaluated the clinical symptoms and
the life quality of the patients. The results suggested that the clinical symptoms of patients
were eased significantly after receiving EGFR-
Int J Clin Exp Med 2016;9(9):18360-18366
The efficacy and safety of icotinib in patients with non-small cell lung cancer
Table 1. Baseline patient characteristics in Icotinib and Gefitinib
groups
Icotinib N=126
N (%)
Gefitinib N=93
N (%)
Gender
Male
34 (27.0)
29 (31.2)
Female
92 (73.0)
64 (68.8)
Age
>70 years
41 (32.5)
33 (35.5)
≤70 years
85 (67.5)
60 (64.5)
Smoking status
Smoker
29 (23.0)
19 (20.4)
Non-somker
97 (77.0)
74 (79.6)
ECOG PS
0 or 1
107 (84.9)
85 (91.4)
≥2
19 (15.0)
8 (8.6)
Stage
III B
9 (7.14)
6 (6.5)
IV
117 (92.9)
87 (93.5)
Histology
Adenocarcinoma
118 (93.7)
90 (96.8)
Non-Adenocarcinoma
8 (6.3)
3 (3.2)
2
BMI (kg/m )
23.91 ± 0.3092 24.26 ± 0.3911
χ2
P-value
0.28 0.5979
0.10 0.7559
0.14 0.7088
1.52 0.2175
0.00 0.9438
0.54 0.4635
0.2694
Table 2. Symptoms and QoL
Symptoms
Chest congestion
Ache
Cough
Eating and sleeping
Onset time (day)
Remission rate (%)
Icotinib
Gefitinib
74.2
80.3
43.3
49.1
66.8
65.2
53.5
37.5
7.633 ± 0.2152 8.101 ± 0.3213
χ2
P-value
0.71
0.50
0.02
4.53
0.4008
0.4781
0.8813
0.0333*
0.2694
χ2
0.00
0.13
2.58
0.00
4.55
P-value
0.9601
0.7184
0.1084
0.9925
0.0328*
*, P<0.05.
Table 3. Response evaluation
Response evaluation
CR
PR
SD
ORR (CR+PR)
DCR (CR+PR+SD)
Icotinib N (%)
14 (11.1)
44 (34.9)
51 (40.5)
58 (53.2)
109 (86.5)
Gefitinib N (%)
11 (12.3)
31 (33.8)
27 (28.5)
42 (45.2)
69 (74.2)
*, P<0.05.
TKI. In terms of loosening chest congestion,
icotinib group was slightly less effective than
gefitinib group (74.2% v.s. 80.3%), but there
was no significant difference between the two
groups (P=0.4008), and the difference in ache
18362
(43.3% v.s. 49.1%, P=0.4781)
and cough (66.8% v.s. 65.2%,
P=0.8813) was also not significant in both groups. Nevertheless, the subjective symptoms of eating and sleeping
which were easier to be influenced by the subjective feelings of patients were improved better in the icotinib
group than gefitinib group
(53.5% v.s. 37.5%, P=0.0333)
with statistical significance.
The onset time of icotinib group was slightly less than that of gefitinib group (7.633 ±
0.2152 v.s. 8.101 ± 0.3213),
but there was no significant
difference between the two
groups (P=0.2694), as shown
in the Table 2.
Response evaluation
CR has no significant difference between icotinib group
and gefitinib group (14 of
126 patients v.s. 11 of 93
patients, P=0.9601). Meanwhile, the number of patients
in PR, SD and PD also has no
significant difference (icotinib group 44, 51, 17 v.s. gefitinib group 31, 27, 24, P>
0.05). In this regard, the ORR
of icotinib was no better than
gefitinib (53.2% v.s. 45.2%,
P=0.9925). However, this study found that the DCR of
icotinib group was much
higher than that of Gefitniib
group (86.5% v.s. 74.2%,
P=0.0328), as shown in the
Table 3.
Adverse reactions
As shown in Table 4, 112
patients in the icotinib group
presented the grade 1-3
rashes on their skin 10-20 days later after taking icotinib; 11 patients suffered the grade 1-3
diarrhea; and 3 patients showed the grade 1-2
liver damage. In gefitinib group, 85 patients
presented the grade 1-3 rashes on their skin
Int J Clin Exp Med 2016;9(9):18360-18366
The efficacy and safety of icotinib in patients with non-small cell lung cancer
Table 4. Adverse reactions
Adverse reactions
Rash
Diarrhea
Liver damage
Icotinib
1-2 (%)
3 (%)
109 (86.5)
3 (2.4)
10 (7.9)
1 (0.8)
3 (2.4)
0 (0)
4 (%)
0 (0)
0 (0)
0 (0)
Gefitinib
1-2 (%)
3 (%)
82 (88.2)
3 (3.1)
6 (6.5)
1 (1.1)
1 (1.1)
0 (0)
4 (%)
0 (0)
0 (0)
0 (0)
χ2
P-value
2.09
0.01
0.04
0.1487
0.9429
0.8393
Figure 1. The PFS and OS of icotinib group and gefitinib group. A. The PFS of icotinib group and gefitinib group. B.
The OS of icotinib group and gefitinib group.
after receiving getitinib; 7 patients suffered the
grade 1-3 diarrhea, and 1 patient showed the
grade 1-2 liver damage. Therefore, it can be
concluded that the patients in two groups show
mild adverse reactions, and the symptoms
have been controlled after giving the antidiarrheic and hepatoprotective therapy. Only two
patients presented the grade 3 adverse reactions. They were allowed to stop taking icotinib
for a while, and to take drugs for the treatment
of adverse reactions until the symptom was
controlled. No more moderate adverse reactions occurred after continuing the application
of icotinib.
According to the Kaplan-Meier analysis, the
PFS and the OS did not significantly differ
between the two treatment groups. The median
PFS was 6.5 months in the icotinib group and
6.3 months in the gefitinib group (Figure 1A),
and the OS was 20.9 months in the icotinib
group and 20.3 months in the gefitinib group
(Figure 1B). The PFS and OS had no significant
difference in the two groups (P>0.05).
Discussion
As a leading cause of the cancer-related mortality both in China and abroad, lung cancer is a
18363
serious threat to the health of most people
[8-10]. Unfortunately, more than 80% of NSCLC
cases are diagnosed in advanced stage (IIIB or
IV). At that stage, the systemic chemotherapy
remains the standard care but provides marginal improvement in survival, resulting in poor
prognosis with a median survival of only 10
months or so [6, 11]. The targeted therapy is
one of the main treatments for patients with
NSCLC [12]. As a novel, orally administered,
and reversible EGFR-TKI, icotinib is the first
homegrown anticancer drug [13]. As the previous studies mainly focused on prolonging the
survival time [14], few researchers analyzed
the life quality of patients. Icotinib was not inferior to gefitinib in terms of progression free survival and overall survival [15]. This study aimed
to compare the efficacy and safety of icotinib
with gefitinib on patients with advanced nonsmall cell lung cancer. Hence, this study provides reference and basis for clinical application for patients with advanced NSCLC.
The abnormal activity of EGFR was mainly
caused by the mutation. According to the state
of EGFR, the NSCLC was divided into mutant
type and wild type [8, 16]. It was observed that
the binding capacity of ATP was decreased
after EGFR mutation, but the affinity of gefitinib
Int J Clin Exp Med 2016;9(9):18360-18366
The efficacy and safety of icotinib in patients with non-small cell lung cancer
was enhanced. It indicated that EGFR-TKIs
could competitively inhibit the ATP’s binding to
the intracellular areas of EGFR and block its
signaling pathway so as to achieve the antitumor effect [17, 18]. Considering that the wildtype EGFR has a high affinity with ATP and a low
affinity with EGFR-TKIs, it will not affect the
function of the wild type EGFR or produce the
anti-tumor effect [16, 19].
According to recent analysis, about 35% of
patients in East Asia were diagnosed as nonsmall cell lung cancer with EGFR mutations
[20]. As the first EGFR TKIs, gefitinib and eriotinib were introduced for clinical application. As
patients with EGFR activating mutations are
notably sensitive to EGFR-TKIs, gefitinib and eriotinib show great curative effects in the treatment of EGFR-mutated NSCLC. Moreover, they
not only improve the survival time of patients,
but also greatly improve their quality of life [21,
22]. Icotinib is the first EGFR-TKI with proprietary intellectual property rights in China and the
third commercially available EGFR-TKI in the
globe [23, 24]. As a randomized, double-blind,
head to head, and phase III trial, ICOGEN is
designed to determine whether icotinib is similar to gefitinib in patients with locally advanced
or metastatic NSCLC. This study proves that
icotinib is not inferior to gefitinib in terms of efficacy and it shows a better safety profile when
compared to gefitinb [6, 7]. Made in China, icotinib has an obvious price advantage compared
with the imported drugs, which can further
reduce the treatment-related costs while promoting the development of Chinese pharmaceutical industry. Therefore, Icotinib has the
potential to become a standard treatment for
NSCLC population with EGFR mutations.
The most frequent treatment-related adverse
reactions were rash and diarrhea. Most adverse
reactions were mild to moderate (grade 1/2),
and very few patients suffered serious adverse
reactions [15, 21]. Hence, this study further
confirmed that there was no difference in terms
of safety between icotinib and gefitinib. As a
retrospective study, this study has several limitations. First of all, the sample size is too small,
with only 126 patients. A higher proportion of
patients and more clinical trials are needed in
the future. To sum up, icotinib is one of effective EGFR-TKIs for pretreating NSCLC population with favorable antitumor activity. Furthe-
18364
rmore, this study further confirmed that it was
clinically equivalent to gefitinib in previously
treated patients with NSCLC. Featured with
superior tolerability, safety and efficacy on
patients with NSCLC, icotinib is of great significance in improving the survival time and life
quality of patients. Hence, it is worthwhile to
spread icotinib in clinical therapy.
Acknowledgements
This work was partly supported by Doctoral
Program Foundation of Henan Cancer Hospital
awarded to Yufeng Wu (No. 201511004).
Disclosure of conflict of interest
None.
Address correspondence to: Dr. Yufeng Wu, Department of Internal Medicine, Henan Cancer
Hospital, No. 127 Dongming Road, Zhengzhou
450008, PR China. Tel: (86)18695829280; Fax:
(86)0371-65588134; E-mail: [email protected]
References
[1]
[2]
[3]
[4]
Shi Y, Sun Y, Ding C, Wang Z, Wang C, Wang Z,
Bai C, Bai C, Feng J, Liu X, Li F, Yang Y, Shu Y,
Wu M, He J, Zhang Y, Zhang S, Chen G, Luo H,
Luo R, Zhou C, Zhou Y, Pang Q, Zhao H, Zhao Q,
Gu A, Ling Y, Huang C, Han B, Jiao S and Jiao H.
China experts consensus on icotinib for nonsmall cell lung cancer treatment (2015 version). Ann Transl Med 2015; 3: 260.
Feng S, Wang Y, Cai K, Wu H, Xiong G, Wang H
and Zhang Z. Randomized Adjuvant Chemotherapy of EGFR-Mutated Non-Small Cell Lung
Cancer Patients with or without Icotinib Consolidation Therapy. PLoS One 2015; 10:
e0140794.
Shi Y, Zhang L, Liu X, Zhou C, Zhang L, Zhang S,
Wang D, Li Q, Qin S, Hu C, Zhang Y, Chen J,
Cheng Y, Feng J, Zhang H, Song Y, Wu YL, Xu N,
Zhou J, Luo R, Bai C, Jin Y, Liu W, Wei Z, Tan F,
Wang Y, Ding L, Dai H, Jiao S, Wang J, Liang L,
Zhang W and Sun Y. Icotinib versus gefitinib in
previously treated advanced non-small-cell
lung cancer (ICOGEN): a randomised, doubleblind phase 3 non-inferiority trial. Lancet Oncol
2013; 14: 953-961.
Janne PA, Gurubhagavatula S, Yeap BY, Lucca
J, Ostler P, Skarin AT, Fidias P, Lynch TJ and
Johnson BE. Outcomes of patients with advanced non-small cell lung cancer treated with
gefitinib (ZD1839, “Iressa”) on an expanded
access study. Lung Cancer 2004; 44: 221230.
Int J Clin Exp Med 2016;9(9):18360-18366
The efficacy and safety of icotinib in patients with non-small cell lung cancer
[5]
[6]
[7]
[8]
[9]
[10]
[11]
[12]
[13]
Zhou Q, Cheng Y, Yang JJ, Zhao MF, Zhang L,
Zhang XC, Chen ZH, Yan HH, Song Y, Chen JH,
Feng WN, Xu CR, Wang Z, Chen HJ, Zhong WZ,
Liu YP and Wu YL. Pemetrexed versus gefitinib
as a second-line treatment in advanced nonsquamous nonsmall-cell lung cancer patients
harboring wild-type EGFR (CTONG0806): a
multicenter randomized trial. Ann Oncol 2014;
25: 2385-2391.
Rosell R, Hu X, Zhang L, Shi Y, Zhou C, Liu X,
Wang D, Song Y, Li Q, Feng J, Qin S, Xv N, Zhou
J, Zhang L, Hu C, Zhang S, Luo R, Wang J, Tan
F, Wang Y, Ding L and Sun Y. The Efficacy and
Safety of Icotinib in Patients with Advanced
Non-Small Cell Lung Cancer Previously Treated
with Chemotherapy: A Single-Arm, Multi-Center, Prospective Study. PLoS One 2015; 10:
e0142500.
Ni J, Liu DY, Hu B, Li C, Jiang J, Wang HP and
Zhang L. Relationship between icotinib hydrochloride exposure and clinical outcome in Chinese patients with advanced non-small cell
lung cancer. Cancer 2015; 121 Suppl 17:
3146-3156.
Yu Y, Liu H, Zheng S, Ding Z, Chen Z, Jin W,
Wang L, Wang Z, Fei Y, Zhang S, Ying K and
Zhang R. Gender susceptibility for cigarette
smoking-attributable lung cancer: a systematic review and meta-analysis. Lung Cancer
2014; 85: 351-360.
Kubota K, Kawahara M, Ogawara M, Nishiwaki
Y, Komuta K, Minato K, Fujita Y, Teramukai S,
Fukushima M and Furuse K. Vinorelbine plus
gemcitabine followed by docetaxel versus carboplatin plus paclitaxel in patients with advanced non-small-cell lung cancer: a randomised, open-label, phase III study. Lancet
Oncol 2008; 9: 1135-1142.
Siegel R, Naishadham D and Jemal A. Cancer
statistics, 2012. CA Cancer J Clin 2012; 62:
10-29.
Macedo-Perez EO, Morales-Oyarvide V, Mendoza-Garcia VO, Dorantes-Gallareta Y, Flores-Estrada D and Arrieta O. Long progression-free
survival with first-line paclitaxel plus platinum
is associated with improved response and progression-free survival with second-line docetaxel in advanced non-small-cell lung cancer.
Cancer Chemother Pharmacol 2014; 74: 681690.
Zhang Y, Sheng J, Yang Y, Fang W, Kang S, He
Y, Hong S, Zhan J, Zhao Y, Xue C, Ma Y, Zhou T,
Ma S, Gao F, Qin T, Hu Z, Tian Y, Hou X, Huang
Y, Zhou N, Zhao H and Zhang L. Optimized selection of three major EGFR-TKIs in advanced
EGFR-positive non-small cell lung cancer: a
network metaanalysis. Oncotarget 2016; 7:
20093-108.
Shi B, Zhang XB, Xu J and Huang XE. Systematic Analysis of Icotinib Treatment for Patients
18365
[14]
[15]
[16]
[17]
[18]
[19]
[20]
[21]
[22]
[23]
with Non-Small Cell Lung Cancer. Asian Pac J
Cancer Prev 2015; 16: 5521-5524.
Lin JJ, Cardarella S, Lydon CA, Dahlberg SE,
Jackman DM, Janne PA and Johnson BE. FiveYear Survival in EGFR-Mutant Metastatic Lung
Adenocarcinoma Treated with EGFR-TKIs. J
Thorac Oncol 2016; 11: 556-65.
Liang W, Wu X, Fang W, Zhao Y, Yang Y, Hu Z,
Xue C, Zhang J, Zhang J, Ma Y, Zhou T, Yan Y,
Hou X, Qin T, Dinglin X, Tian Y, Huang P, Huang
Y, Zhao H and Zhang L. Network meta-analysis
of erlotinib, gefitinib, afatinib and icotinib in patients with advanced non-small-cell lung cancer harboring EGFR mutations. PLoS One
2014; 9: e85245.
Paez JG, Janne PA, Lee JC, Tracy S, Greulich H,
Gabriel S, Herman P, Kaye FJ, Lindeman N,
Boggon TJ, Naoki K, Sasaki H, Fujii Y, Eck MJ,
Sellers WR, Johnson BE and Meyerson M.
EGFR mutations in lung cancer: correlation
with clinical response to gefitinib therapy. Science 2004; 304: 1497-1500.
Sirotnak FM, Zakowski MF, Miller VA, Scher HI
and Kris MG. Efficacy of cytotoxic agents
against human tumor xenografts is markedly
enhanced by coadministration of ZD1839 (Iressa), an inhibitor of EGFR tyrosine kinase.
Clin Cancer Res 2000; 6: 4885-4892.
De Rosa V, Iommelli F, Monti M, Fonti R, Votta
G, Stoppelli MP and Del Vecchio S. Reversal of
Warburg Effect and Reactivation of Oxidative
Phosphorylation by Differential Inhibition of
EGFR Signaling Pathways in Non-Small Cell
Lung Cancer. Clin Cancer Res 2015; 21: 51105120.
Zhang HX, Xiong HX and Li LW. Investigation on
the protein-binding properties of icotinib by
spectroscopic and molecular modeling method. Spectrochim Acta A Mol Biomol Spectrosc
2016; 161: 88-94.
Kim YS, Cho EK, Woo HS, Hong J, Ahn HK, Park
I, Sym SJ, Kyung SY, Kang SM, Park JW, Jeong
SH, Park J, Lee JH and Shin DB. Randomized
Phase II Study of Pemetrexed Versus Gefitinib
in Previously Treated Patients with Advanced
Non-small Cell Lung Cancer. Cancer Res Treat
2016; 48: 80-7.
Ni J and Zhang L. Evaluation of Three Small
Molecular Drugs for Targeted Therapy to Treat
Nonsmall Cell Lung Cancer. Chin Med J (Engl)
2016; 129: 332-340.
Singh D, Attri BK, Gill RK and Bariwal J. Review
on EGFR inhibitors: critical updates. Mini Rev
Med Chem 2016; 16: 1134-66.
Li X, Qin N, Wang J, Yang X, Zhang X, Lv J, Wu Y,
Zhang H, Nong J, Zhang Q and Zhang S. Clinical Observation of Icotinib Hydrochloride for
Advanced Non-small Cell Lung Cancer Patients
with EGFR Status Identified. Zhongguo Fei Ai
Za Zhi 2015; 18: 734-739.
Int J Clin Exp Med 2016;9(9):18360-18366
The efficacy and safety of icotinib in patients with non-small cell lung cancer
[24] Yao S, Qian K, Wang R, Li Y and Zhang Y. Comparison of the Efficacy and Safety of Icotinib
with Standard Second-line Chemotherapy in
18366
Previously Treated Advanced Non-small Cell
Lung Cancer. Zhongguo Fei Ai Za Zhi 2015; 18:
369-373.
Int J Clin Exp Med 2016;9(9):18360-18366