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  Table of Contents  
Year : 2017  |  Volume : 54  |  Issue : 1  |  Page : 215-222

Retrospective analysis of icotinib neoadjuvant therapy of 63 lung cancer patients

Department of Thoracic Surgery, PLA General Hospital, Beijing 100853, China

Date of Web Publication1-Dec-2017

Correspondence Address:
Dr. T Wang
Department of Thoracic Surgery, PLA General Hospital, Beijing 100853
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0019-509X.219585

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 » Abstract 

OBJECTIVE: This study aims to explore the feasibility of icotinib neoadjuvant therapy for nonsmall cell lung cancer (NSCLC). MATERIALS AND METHODS: This was a retrospective analysis of the clinical data for 63 NSCLC patients (61 cases of adenocarcinoma and two cases of squamous cell carcinoma) receiving surgical resection of lung lesions after oral intake of icotinib from December 2011 to November 2013 in the PLA General Hospital. Preoperative oral intake of the patients was icotinib 125 mg tid, drug side effects were evaluated according to the American National Cancer Institute Common Toxicity Criteria Version 4.0; computed tomography scan was done on the day taking medicine and 2 weeks later to determine tumor changes. After oral intake of Icotinib for 2 to 22 weeks (5 cases for 2 weeks,13 cases for 3 to 22 weeks), all patients receive surgical resection of lung cancer lesions, and testing of removed tumor to evaluate the epidermal growth factor receptor (EGFR) gene mutation status was performed by fluorescence polymerase chain reaction. The patients with sensitive EGFR mutations receive Icotinib as postoperative adjuvant therapy. RESULTS: Side effects of medication within 2 weeks included rash (44.4%, 28/63), dry skin (34.9%, 22/63), diarrhea (14.3%, 9/63), and oral ulcer (1.6%, 1/63); there were no icotinib-associated thoracic surgery complications during the perioperational period. 71.4% patients (45/63) achieve an average reduction of 23.5% ±10.7%(10%-53.5%) after 2 weeks medication of Icotinib(regressive tumor[RT]) .28.6% patients(18/63) achieve stable tumor(ST),enlargement of 8.7% to reduction of 8.7% of the maximum diameter of lung cancer after 2 weeks medication of Icotinib. Of the RT group, 68.9% (31/45) of the tumors were detected with EGFR-sensitive mutation (exon 19 or 21 mutation), 24.4% (11/45) with wild-type EGFR, and three cases of exon 20 mutation. Of the ST group, 77.8% (14/18) were detected with wild-type EGFR, three cases of exon 20 mutation, and one case of exon 19 deletion mutation (tumor reduction by 7.9%). 45 cases in RT group and 1 case with EGFR 19 exon metation in ST group receive Icotinib as adjuvant therapy. Among 45 cases in RT group and 18 cases in ST group, there was no difference in gender, age, smoking history, tumor diameter, tumor differentiation degree, and incidence of side effects (P = 0.076). There was significant difference (P < 0.0001) in terms of symptom remission rate after medication and EGFR gene-sensitive mutation rate in RT and ST groups. CONCLUSION: Icotinib neoadjuvant therapy for NSCLC is safe and feasible, and the reactivity of lung cancer patients to icotinib can be determined within 2 weeks of medication. People sensitive to preoperative selection of drugs can more accurately determine the sensitivity of tumors to drugs, thus providing evidence for postoperative adjuvant therapy.

Keywords: Epidermal growth factor receptor gene mutation, icotinib, neoadjuvant therapy, nonsmall cell lung cancer

How to cite this article:
Wang T, Liu Y, Zhou B, Hao S, Wang Z, Liang N, Liu J, Wang S. Retrospective analysis of icotinib neoadjuvant therapy of 63 lung cancer patients. Indian J Cancer 2017;54:215-22

How to cite this URL:
Wang T, Liu Y, Zhou B, Hao S, Wang Z, Liang N, Liu J, Wang S. Retrospective analysis of icotinib neoadjuvant therapy of 63 lung cancer patients. Indian J Cancer [serial online] 2017 [cited 2022 Oct 2];54:215-22. Available from:

 » Introduction Top

Lung cancer is one of the most common cancers worldwide, and there are about 12,000,000 people die from lung cancer every year ranking the first most fatal cancer. For nonsmall cell lung cancer (NSCLC), except Stage Ia, even though Stage Ib–IVb patients have the opportunity for lesion resection, systemic therapy (chemotherapy) is still required as postoperative treatment to eliminate potential metastatic lesions (NCCN and ACCP Guide). However, the benefit rate of chemotherapy is not higher than 35%;[1],[2] therefore, the clinical effect of postoperative adjuvant chemotherapy is unknown.

In recent years, the application studies of epidermal growth factor receptor (EGFR)-targeting tyrosine kinase inhibitor (TKI) in NSCLC, especially carcinoma-sensitive patients, demonstrate TKI's remarkable curative effect and tolerance, bringing a new method of treatment for potential TKI beneficiaries. However, similar to the postoperative adjuvant chemotherapy, the effectiveness of TKI application in NSCLC patients after surgery is still not certain. Although treatment strategies can be indirectly determined by discovering patients with TKI-sensitive mutations through EGFR testing, the rate of evaluation accuracy is limited due to the heterogeneity of tumors.[3],[4]

Tumor sensitivity to chemotherapy can be revealed through preoperative medication in neoadjuvant chemotherapy reducing surgical difficulty or increasing the chance of resection after reducing tumor-node-metastasis (TNM) stage and killing potential metastatic lesions; despite the above advantages, the effectiveness of chemotherapy is limited and serious side effects decrease the surgical tolerance of patients increasing the operation risk. Patients have to wait for more than 4 weeks after chemotherapy before receiving surgical operation. The above-mentioned factors may lead to progressed growth of tumor in patients losing the chance for surgery.[5],[6] In addition, the educational and cultural background of the Chinese people may cause quite a number of patients to resent chemotherapy. In theory, beneficiaries of EGFR-TKI neoadjuvant therapy can enjoy benefits similar to neoadjuvant chemotherapy but less severe side effects; therefore, whether TKI can be used as the neoadjuvant therapy for NSCLC has obvious clinical significance. A few small sample reports showed that NSCLC patients with EGFR genetic mutations become capable of receiving surgical resection after gefitinib neoadjuvant therapy.[7]

Icotinib is a Chinese Food and Drug Administration-approved oral EGFR-TKI drug appearing on the market in 2010. In clinical trials (ICOGEN Research), icotinib has achieved similar curative effects to gefitinib in treating Stage III advanced NSCLC patients who experienced previously platinum chemotherapy failure but with much less severe side effects.[8] Based on the research above, we retrospectively analyzed the relevant issues about icotinib neoadjuvant therapy for NSCLC, such as safety, effectiveness, and effects of drug on operations, particularly the feasibility of screening and identifying postoperative adjuvant therapy beneficiaries by drug medication.

 » Materials and Methods Top

Clinical data

This was a retrospective analysis of NSCLC patients receiving surgical resection of lung lesions after oral intake of icotinib from December 2011 to November 2013 in the PLA General Hospital. Of 289 patients who take Icotinib initially, we screen out the patients by the criteria: NSCLC, treatment naive, fully chest CT profling, PS=0 or KPS=90, resection of entire lung cancer, EGFR mutation testing. Totally, 63 patients met such conditions.

Tumor staging was performed according to the International Association for the Study of Lung Cancer.[9]

Treatment plan

All patients recieve Icotinib treatment, 125mg Tid. All patients received chest CT examination on the day taking medication and after 2 weeks of medication.

Fifty patients received resection of lung lesions immediately after the second chest scan.

The 2-week medication was proven effective for 13 patients who received resection of lung lesions after extended medication owing to various reasons. The 13 patients took the second chest CT, carcinoembryonic antigen, and transaminase 1 day before surgery. The 13 patients took chest CT scan, CEA and liver function test 1 day before surgery. And all patients stopped medication 1 day before surgery. All patients stopped medication 1 day before the surgery.

On the basis of operation indications, 45 patients received lobectomy and 18 cases of wedge or segmental resection. All patients received hilar and mediastinal lymph nodes resection and pathological staging. One case of IIIb (supraclavicular lymph node metastasis), four cases of IVa (malignant pleural effusion), and two cases of IVb (solitary bone metastasis and brain metastasis) received lesion resection after TKI treatment and disappearance of pleural effusion and extrathoracic metastasis. Two cases of IVa patients with pleural metastasis discovered in operation. All operations were undergone through video-assisted thoracoscopy (VATS) or lateral incision approach and by the same surgeon to ensure the stability of operation parameters.

Fluorescent polymerase chain reaction (Beijing ACCB Biotech Ltd.) was used for detection of EGFR genetic mutations in tumor samples.

Drug side effects and efficacy evaluation

Side effects of the drug were evaluated according to the common toxicity criteria American National Cancer Institute Version 4.0. Taking into account tumor response to drugs and effect of respiratory depth on CT results, the patients were divided into regressive tumor (RT) group: Maximum tumor diameter reduction by over 10% after medication and stable tumor (ST) group: Maximum tumor diameter reduction by <10% or slight enlargement of tumor.

Data analysis

SPSS 16 software (IBM Corporation, USA) was applied for statistical analysis. 45 patients in RT group and 18 patients in ST group take Chi-square test for gender, age, smoking status, tumor size, adverse effects, rate of EGFR mutation in two group. Logistic regression analysis was applied to analyze the relationship between tumor response rate and clinical features of icotinib treatment. P < 0.05 was considered statistically significant.

 » Results Top

Clinical features of the patients in question

Totally, 63 NSCLC patients on neoadjuvant therapy of icotinib including 28 males and 35 females were involved in the study. The mean age was 57.8 ± 9.5 years (37–78-year, median age 58-years). 29 patients have lung cancer symptoms(including cough, chest pain, blood in phlegm).

63 patients have pathological diagnosis, 61 patients adenocarcinoma and 2 patients squamous cell carcinoma. Tumor TNM stage was between Stage Ia and Stage IVb. EGFR gene mutation testing of the removed tumor for all patients was performed, including 25 cases of wild-type and 38 cases of mutations: Exon 21 mutation in twenty patients (L858R, two cases accompanied with Q787Q exon 20 mutation), exon 19 deletion mutation in 12 patients, exon 20 mutation (Q787Q) in six patients. The clinical features of the patients are shown in [Table 1].
Table 1: Clinical features

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Common side effects after 2 weeks of medication include rash, dry skin, diarrhea, and oral ulcer. Only three patients suffered second-degree side effects and no case of third-degree side effects [Table 2]. Among the 33 cases in RT group with incidence of side effects (73.3%, 33/45), 14 cases suffered more than two side effects. Nine cases in group ST (50%, 9/18) suffered side effects. Noticeably, first-degree side effects demonstrated different severity in the two groups of patients – side effects in ST group were obviously less severe than those in RT group. Drug tolerance for all patients was high and no patient discontinued medication or delayed operation due to adverse side effects.
Table 2: Side effects of icotinib neoadjuvant therapy (2-weeks)

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All operations were performed through VATS or lateral incision approach. Unlike conventional lung cancer surgery, there may be some condition of tissue adhesion after the medication of Icotinib [Figure 1], but there were no inseparable vascular conditions. Vascular fragility seems to be increased, but no vascular rupture occurred as a result.
Figure 1: Case No. 5 lobectomy of theupper left lobe

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All patients recovered well and stitches at incision were taken out 10 days after surgery; no abnormal cicatrization (resume oral intake of icotinib after taking out stitches as appropriate due to concern about possible influence on cicatrization) was noted. Only one patient (with dual primary carcinoma) experienced delayed healing of breast flap due to radical mastectomy (4 weeks of preoperative oral intake of icotinib). The delayed healing after debridement dragged on for 1 month before medication was resumed and no other complications attributed to icotinib subsequently. Another patient also with dual primary carcinoma of gastric antrum cancer received distal gastrectomy (2 weeks of preoperative oral intake of icotinib) with normal abdominal recovery.

Long-term follow-up (1–20 months) results showed no other short- and long-term operation complications for all patients.

Clinical effects

About 72.4% (21/29) of the patients with symptoms achieved obvious palliation after 4.7 ± 1.9 days (2–10 days, median 5 days) of medication and were CT-proved to be the RT patients. 27.6% (8/29) of the patients with symptoms failed to achieve any relief after 2 weeks of medication and were all ST patients. Apparently, there was significant difference (100% vs. 0%) in the relief rate of medication for the 21 cases in RT group and the eight cases in ST group.

Change of tumor size was visually noticeable between the two CT scans before and after medication [Figure 2]. Thirteen patients prolonged medication for various reasons, and the preoperative CT scan results showed that 12 (92.3%) of 13 cases could see tumor reduction up to PR Criteria of RECIST Version 1.1. [Figure 2]; one patient in Stage IVb experienced lesion reduction by 14.4% after 18 weeks of medication and the brain metastases completely disappeared. The patient received lesion resection after cancer downgrade [Figure 3] and [Table 3].
Figure 2: Case No. 11

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Figure 3: Case No. 12. Left parietal lobe solitary metastasis (T2-weighted image)

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Table 3: Prolonged neoadjuvant tyrosine kinase inhibitor therapy longer than 2 weeks

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Nine (50%) of the 18 cases in ST group (28.6%, 18/63) experienced a maximum tumor diameter enlargement by 2.5% ± 2.6% (0.3%–8.7%) on average and the other nine cases (50%) experienced a maximum tumor diameter reduction by 3.2% ± 3.1% (0.3%–8.7%) on average after 2 weeks of medication. Lesion resection was performed on all patients after 2 weeks [Figure 4].
Figure 4: Waterfall response plot after 2 weeks of Icotinib

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Epidermal growth factor receptor mutation analysis

EGFR genetic mutation testing was performed for 63 patients in this study. Tumor in 96.9% (31/32) patients with TKI-sensitive mutations (EGFR exon 19 or 21 mutation) shrank by over 10% within 2 weeks of medication; tumor in 50% (3/6) patients with EGFR exon 20 mutation (TKI-insensitive) shrank by over 10% within 2 weeks of medication; tumor in 44% (11/25) patients with wild-type EGFR mutation shrank by over 10% within 2 weeks of medication; patients with EGFR-sensitive mutation were more prone to responding to the drug (verified by bilateral exact probability method, P < 0001) [Figure 4] and [Table 4].
Table 4: Baseline comparison - regressive tumor group and stable tumor group

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Of the 45 patients in the RT group, tumor was seen in 11 (24.4%) with EGFR exon 19 mutation shrank by 26.5% ± 7.4% (15.6%–40.4%, median 28.9%) within 2 weeks of TKI drug medication; tumor in 20 cases (44.4%) with EGFR exon 21 mutation shrank by 23.4% ± 11.2% (12.3%–53.5%, median 20.6%) within 2 weeks of TKI drug medication; and tumor in 11 cases (24.4%) with EGFR wild-type shrank by 23.1% ± 13.2% (10%–52.4%, median 22.6%) within 2 weeks of TKI drug medication. In the RT group, there was no difference in tumor diameter reduction among 11 cases of exon 19 mutation, 20 cases of exon 21 mutation, and 11 cases of wild type after 2 weeks of TKI medication (Wilcoxon rank test, P = 0.2645) [Figure 4].

In the RT group, wild-type and exon 20 mutations' (TKI-insensitive mutant) patients accounted for 31.1% (14/45) and the population ratio between TKI-insensitive and TKI-sensitive EGFR mutations was 1:2.21 (14/31).

Analysis of related factors for clinical effect

Chi-square test verified that there was no difference in gender, age, smoking history, tumor diameter before medication, the incidence of side effects, and degree of tumor differentiation for patients in the RT and ST groups (P = 0.262, 0.808, 0.071, 0.373, 0.076, 0.137). However, RT and ST groups of patients demonstrated significant difference in EGFR-sensitive mutation rate (P< 0.0001). Baseline comparison of RT and ST groups is shown in [Table 4].

Univariate analysis was performed between gender, age, smoking history, tumor diameter before treatment, side effects of drugs, degree of tumor differentiation, and clinical effects of icotinib to identify related factors to efficacy. Still, no statistically significant factor was discovered. Relationship between clinical features and icotinib efficacy is shown in [Table 5].
Table 5: Relationship between clinical features and icotinib efficacy

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 » Discussion Top

Lung cancer is malignant cancer with the highest morbidity and mortality in China and still on the rise. EGFR-TKI has been introduced to treat partially patients with the advanced NSCLC, especially adenocarcinoma patients accompanied with EGFR-sensitive mutations. For sensitive people, to achieve identical curative effects, TKI medication enjoys distinct advantages in compliance and life quality compared with chemotherapy. For NSCLC patients received lesion resection, whether EGFR-TKI should be applied as the first-line drugs to reduce the recurrence probability in the long run is still as uncertain clinically as postoperative adjuvant chemotherapy, although its suitability can be indirectly evaluated by EGFR mutation testing of the removed tumor since resection of lesion disables control unless tumor recurs and contrast is thus established.

In theory, similar to the neoadjuvant chemotherapy, neoadjuvant TKI medication can help us determine the reactivity of tumor to drugs before lesion resection. To date, there is no literature about neoadjuvant therapy of icotinib in treating patients with NSCLC. This study is the first clinical research on retrospectively analyzing icotinib neoadjuvant therapy for NSCLC.

Icotinib medication can result in the common side effects of EGFR-TKI drugs, such as the rash incidence rate of 41% and diarrhea incidence rate of 22%,[8] as ICOGEN research reports. Patients in this study demonstrated common side effects of rash, dry skin, diarrhea, and oral ulcer in very rare cases within 2 weeks of oral intake of icotinib, similar to reports in relevant literature. All patients could tolerate side effects of icotinib therapy, and the majority of adverse reaction is first degree. Compared with other EGFR-TKI drugs in the same class reported in the literature for neoadjuvant therapy, icotinib has relatively light toxicity. Rizvi et al.[10] applied gefitinib as neoadjuvant therapy to early-stage NSCLC patients to observe the relationship between tumor response and EGFR genetic mutations, and the results showed that the incidence rate of toxicity reactions was 52% for rash, 32% for diarrhea, one patient with third-degree diarrhea in the fifty patients and one patient discontinued use of icotinib due to intolerance to rash. Besides the drug difference, duration of neoadjuvant therapy is the only distinction between this study and Rizvi et al., the latter strictly abides by 3-week dosage. In our study, 50 (79.4%) of 63 patients received tumor resection after 2 weeks of medication and only 13 (20.6%) patients received tumor resection after over 2 weeks of medication due to various reasons without deterioration of side effects over 2 weeks of medication; therefore, evaluation of side effects of icotinib within 2-week medication does not differ from evaluation after longer period of icotinib therapy.

The optimal timing for surgery on NSCLC patients received TKI neoadjuvant therapy and drug effects on surgery is rarely involved in literature. Our experience showed that medication can be taken till 1 day before surgery, unlike neoadjuvant chemotherapy which requires 3–5 weeks after stopping chemotherapy to receive surgical operations. Fifty patients in the study were operated on immediately after 2 weeks of medication and other 13 patients after 3–22 weeks. Similar to the neoadjuvant chemotherapy, tissue fibrosis can be resulted increasing the operational difficulty, and severe adhesion of tissue space was also discovered for patients in the study, especially in the isolation of pulmonary vessels and vascular sheath; in the mediastinal lymph node dissection, strengthen toughness of lymphoid tissue was apparent. No pulmonary vascular dissociation difficulty in this study may be attributed to any perivascular metastasis lymph node in patients in this study. Literature reports that with the metastasis lymph nodes around the blood vessels, local fibrosis after neoadjuvant therapy may lead to vascular dissociation difficulties and extended resection.

Chemotherapy can significantly affect tissue cicatrization, but the influence of TKI therapy on tissue cicatrization is not literally reported. Since conventional incision was not applied to patients in this study, despite well-controlled length of lateral incision within 10 cm, no chest incision or difficult close-up of drainage or bronchopleural fistula or other relevant complications of difficult healing of tissue stump, the effects of TKI therapy on tissue healing under special circumstances should not be ignored, such as the short-term delayed healing of breast flap due to radical mastectomy for the patient receiving right upper lobectomia simultaneously. According to the hands-on experience in this study, icotinib neoadjuvant therapy for NSCLC can increase the dissociation difficulty in operation and no special treatment is required for the perioperational period. TKI medication can cease just 1 day before surgery which is the major difference from neoadjuvant chemotherapy. The above description concludes that preoperative icotinib neoadjuvant therapy for NSCLC is safe and will not increase the operation risks significantly.

Evaluation of the curative effects was performed based on 2-week medication, rather than the traditional period (4 weeks). Short-time window enables patients with inefficacy of medication to be treated with operation the soonest possible, avoiding any delay of the disease while saving cost of treatment. Reduction of the maximum tumor diameter by over 10% was applied as the evaluation standard for effective treatment, rather than the RECIST Criteria [11] (reduction of tumor size by over 30%) because effective TKI therapy can display a visually noticeable change of tumor on CT after 2 weeks of medication (to be reflected in a retrospective study with a larger sample size in the future article); further, with the continued therapy, RECIST PR Criteria will be gradually reached. For example, among the 13 cases of preoperative TKI medication for more than 3 weeks, 92.3% of the patients achieved the tumor reduction by over 30% on the subsequent CT review. There was one patient with exon 21 mutation, though the lung tumor reduction failed to meet PR Criteria, the brain metastases disappeared completely, therefore, still reaching the down-staging goal of TKI neoadjuvant therapy. For Stage IVb patients with distal metastasis, whether the practice of eradicating extrathoracic metastasis before resection of lung lesions will improve long-run survival and life quality as well as reduce the probability of future drug resistance of TKI therapy still requires long-term follow-up and larger sample size. Similarly, we evaluate the 18 cases with tumor size change <10% to be inefficacy and clinical features also indirectly support our judgment, such as the 17 patients without EGFR sensitive mutation (only one patient with exon 19 mutations, tumor reduction by 7.9% only), side effects occurred in nine cases only, and are pretty light. After longer application of the medication, the disease will continue to maintain a stable or progressed status for patients of this category (to be reflected in a retrospective study with a larger sample size in the future article).

EGFR testing results of the RT group also verified that 68.9% (31/45) of the patients with efficacy were EGFR sensitive (exon 19 or 21 mutation), similar to the reported patterns in literature; however, a significant proportion (31.1%, 14/45) of the patients in the RT group were wild type or exon 20 mutation and further testing indicated that the tumor reduction speed (reduction percentage) is not inferior to that of sensitive mutations. The above findings clearly illustrate that predicting the efficacy of TKI medication by EGFR genetic mutation status falls short, at least will leave outpatients with wild-type or exon 20 positive who are generally categorized as patients incapable of benefiting from EGFR-TKI therapy, and without the preoperative medication verification, they would have missed the opportunity for TKI therapy. Therefore, the accuracy of screening patients through preoperative TKI neoadjuvant therapy is superior to the currently prevailing genetic mutation testing. In view of the fact that this study was based on carcinomas' specimens obtained from surgical operations, the probability of genetic detection error is far lower than fine-needle aspiration; the possibility of failure to detecting exon 19 or exon 21 mutation due to medication is questionable because five patients in the RT group on medication for over 6 weeks (up to 22 weeks) detected exon 19 or 21 mutation in the resection specimens, so there is slim possibility of 2-week medication of EGFR-TKI influencing genotype of cancer tissues. As for the unsatisfactory tumor reduction rate of one patient in the ST group with exon 19 deletion mutation, it might be attributed to short period of medication or exon 19 mutation only indicates that patients might benefit from TKI therapy, but not certainly due to heterogeneity of tumor and complexity of genotype.

Since there are omissions in the EGFR mutation screening for beneficiaries, determining TKI beneficiary groups by general clinical features, such as not smoking, woman, Asian descendant, adenocarcinoma, and tumor differentiation degree, is simple, convenient, and easy to practice. Analysis of the relevant factors and the efficacy of icotinib in the RT group, gender, age, smoking history, tumor size, and the degree of tumor differentiation were all of no predictive significance for the efficacy of TKI, and there was no difference in clinical characteristics of the patients in the RT and ST groups. The above findings further demonstrate that screening TKI beneficiaries through general clinical features will also leave out a large number of potential beneficiary patients. In summary, on the basis of verified safety, preoperative medication can judge the drug-sensitive patients more accurately.

Drug efficacy can be evaluated at the CT review after 2 weeks of medication to CT to confirm the change of tumor size. However, we found out that 32 of 33 patients with symptoms in the RT group experienced definitive symptom relief within 1 week of medication which is remarkably distinctive from the nine cases in the ST group without definitive symptom relief after TKI therapy.

Research of Pérez-Soler et al.[12] concluded that rash can be used as an index of predicting erlotinib clinical efficacy. While Emery et al.[13] showed that despite the correlation between rash and clinical efficacy of erlotinib, such correlation failed to appear in the research on gefitinib application. In our study, the incidence rate of side effects in the RT group was higher than that in the ST group (33/45 and 9/18, respectively); although the two groups did not reach the ideal statistical difference (P = 0.076), the clinical manifestations responsive to side effects in the patients of the ST group were obviously less severe than the RT group (all first-degree side effects). The trend has revealed that with the constantly increasing number of samples, statistical difference will manifest itself; therefore, it is worthy of further studies about at an early stage identifying icotinib beneficiaries through the incidence rate and severity of side effects. On the other hand, it cannot be concluded that patients without apparent side effects of drugs will not benefit from TKI therapy, and the viewpoint was supported by the analysis of the relevant factors to drug efficacy in the RT group (P = 0.239).

 » Conclusion Top

Icotinib as the preoperative neoadjuvant therapy for NSCLC is safe and feasible, and the sensitivity of tumor to drugs can be accurately judged from the improved symptoms and sequence CT scans within 2 weeks of medication. Selection of icotinib beneficiaries through drugs is superior to other methods.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

 » References Top

Cardenal F, López-Cabrerizo MP, Antón A, Alberola V, Massuti B, Carrato A, et al. Randomized phase III study of gemcitabine-cisplatin versus etoposide-cisplatin in the treatment of locally advanced or metastatic non-small-cell lung cancer. J Clin Oncol 1999;17:12-8.  Back to cited text no. 1
Sandler AB, Nemunaitis J, Denham C, von Pawel J, Cormier Y, Gatzemeier U, et al. Phase III trial of gemcitabine plus cisplatin versus cisplatin alone in patients with locally advanced or metastatic non-small-cell lung cancer. J Clin Oncol 2000;18:122-30.  Back to cited text no. 2
Kimura H, Kasahara K, Kawaishi M, Kunitoh H, Tamura T, Holloway B, et al. Detection of epidermal growth factor receptor mutations in serum as a predictor of the response to gefitinib in patients with non-small-cell lung cancer. Clin Cancer Res 2006;12:3915-21.  Back to cited text no. 3
Kimura H, Suminoe M, Kasahara K, Sone T, Araya T, Tamori S, et al. Evaluation of epidermal growth factor receptor mutation status in serum DNA as a predictor of response to gefitinib (IRESSA). Br J Cancer 2007;97:778-84.  Back to cited text no. 4
De Marinis F, Gebbia V, De Petris L. Neoadjuvant chemotherapy for stage IIIA-N2 non-small cell lung cancer. Ann Oncol 2005;16 Suppl 4:iv116-22.  Back to cited text no. 5
Migliorino MR, De Petris L, De Santis S, Cipri A, Belli R, Condò S, et al. Locally advanced non-small cell lung cancer: Role of induction chemotherapy in resectable N2 disease. Ann Oncol 2006;17 Suppl 2:ii28-31.  Back to cited text no. 6
Takamochi K, Suzuki K, Sugimura H, Funai K, Mori H, Bashar AH, et al. Surgical resection after gefitinib treatment in patients with lung adenocarcinoma harboring epidermal growth factor receptor gene mutation. Lung Cancer 2007;58:149-55.  Back to cited text no. 7
Shi Y, Zhang L, Liu X, Zhou C, Zhang L, Zhang S, et al. Icotinib versus gefitinib in previously treated advanced non-small-cell lung cancer (ICOGEN): A randomised, double-blind phase 3 non-inferiority trial. Lancet Oncol 2013;14:953-61.  Back to cited text no. 8
Detterbeck FC, Boffa DJ, Tanoue LT. The new lung cancer staging system. Chest 2009;136:260-71.  Back to cited text no. 9
Rizvi NA, Rusch V, Pao W, Chaft JE, Ladanyi M, Miller VA, et al. Molecular characteristics predict clinical outcomes: Prospective trial correlating response to the EGFR tyrosine kinase inhibitor gefitinib with the presence of sensitizing mutations in the tyrosine binding domain of the EGFR gene. Clin Cancer Res 2011;17:3500-6.  Back to cited text no. 10
Nishino M, Jackman DM, Hatabu H, Yeap BY, Cioffredi LA, Yap JT, et al. New response evaluation criteria in solid tumors (RECIST) guidelines for advanced non-small cell lung cancer: Comparison with original RECIST and impact on assessment of tumor response to targeted therapy. AJR Am J Roentgenol 2010;195:W221-8.  Back to cited text no. 11
Pérez-Soler R, Chachoua A, Hammond LA, Rowinsky EK, Huberman M, Karp D, et al. Determinants of tumor response and survival with erlotinib in patients with non-small-cell lung cancer. J Clin Oncol 2004;22:3238-47.  Back to cited text no. 12
Emery IF, Battelli C, Auclair PL, Carrier K, Hayes DM. Response to gefitinib and erlotinib in non-small cell lung cancer: A restrospective study. BMC Cancer 2009;9:333.  Back to cited text no. 13


  [Figure 1], [Figure 2], [Figure 3], [Figure 4]

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]

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