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Efficacy and Influence Factors of Icotinib Hydrochloride in Treating Advanced Non-Small Cell Lung Cancer

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Efficacy and Influence Factors of Icotinib Hydrochloride in Treating Advanced Non-Small Cell Lung Cancer European Review for Medical and Pharmacological Sciences 2017; 21: 266-274 Efficacy and influence factors of icotinib hydrochloride in treating advanced non-small cell lung cancer X.-H. MA, T.-D. TIAN, H.-M. LIU, Q.-J. LI, Q.-L. GAO, L. LI, B. SHI Integrated TCM & Western Medicine Department, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, China Abstract. – OBJECTIVE: To evaluate the effi- Introduction cacy and safety of icotinib hydrochloride in the treatment of patients with advanced non-small In the most parts of the world, the lung cancer cell lung cancer (NSCLC) and discuss the influ- ranks on the top list between global tumor occur- ence factors on efficacy. rence and mortality, which seriously threatens PATIENTS AND METHODS: 120 treatment-ex- the human health and life. Lung cancer mainly perienced patients confirmed by pathology or includes non-small cell lung cancer (NSCLC) cytology with stage III B-IV non-small cell lung cancer took icotinib hydrochloride and erlotinib and small cell lung cancer (SCLC), in which orally until the occurrence of disease progres- NSCLC accounts for 80% and has a five-year 1,2 sion or serious adverse reactions. Then, the effi- survival rate of only 12-15% . Due to the oc- cacy of icotinib hydrochloride and the related in- cult features of lung cancer at the early stages, fluence factors were analyzed. over 70% patients with lung cancer have missed RESULTS: In icotinib hydrochloride group, the the chance of surgery when they felt ill. More- response rate and the disease control rate were over, less than 1/3 NSCLC patients are early 30.00% and 65.00%, and the median progres- sion-free survival time was 179 days (95% CI: diagnosed and subjected to excision. Although 103.21-254.78); in erlotinib group, the response the traditional chemotherapy can reduce mor- rate and the disease control rate were 25.00% and tality to some extent, it just only increases the 56.70%, and the median progression-free surviv- one-year survival rate from 20% to 29%3. Also, al time was 121 days (95% CI: 95.05-146.94). More- the traditional chemotherapy has great toxicity over, the objective response rate and the disease and side effects that are intolerable for advan- control rate of second-line therapy were both su- perior to the third-line and above therapy. The ob- ced patients with poor health conditions. Befo- jective response rate of patients with complete re application of the targeted therapy to clinical response/partial response/stable disease after treatment, the systemic chemotherapy was the the first-line therapy was higher than that of pa- primary method of treating advanced NSCLC. tients without response after the first-line thera- However, with the development of molecular py (p<0.05), and the significant differences exist- biology and further study of tumor signal tran- ed in the objective response rate and the disease sduction, the targeted therapy has been a signifi- control rate among mutant group, wild-type group, 4 and unknown group (p<0.05). The response rate cant method . Epidermal growth factor receptor and the disease control rate of erythra group were (EGFR) is a major signal transduction pathway, higher than those of non-erythra group (p<0.05). which regulates onset, growth and apoptosis of It was showed in the univariate analysis that the tumor, and it was turned out in many studies that progression-free survival was correlated with the NSCLC with EGFR mutants has special clinical smoking status and the epidermal growth factor characteristics and progressions. The epidermal receptor gene mutations. CONCLUSIONS: The icotinib hydrochloride is growth factor receptor tyrosine kinase inhibi- effective and safe in treating the treatment-ex- tors (EGFR-TKIs) have been widely applied to perienced patients with advanced NSCLC, espe- the second-line therapy of advanced NSCLC. cially for patients with sensitive mutations. Through working on the epidermal growth factor receptor tyrosine kinase, it was discovered that Key Words: the EGFR can block the signal transduction to Icotinib hydrochloride, Non-small cell lung cancer, Efficacy, Safety, Erlotinib. inhibit tumor growth, thereby prolonging the life of patients, especially lung cancer patients with 266 Corresponding Author: Tong-de Tian, MD; e-mail: [email protected] Efficacy and influence factors of icotinib hydrochloride in treating advanced non-small cell lung cancer EGFR mutants5-7. As the convenient way takes Clinical data mild adverse reactions with better tolerance than From March 2010 to March 2016, 120 patients the second-line therapy, its representative me- met the above inclusion and exclusion criteria. The dicines gefitinib and erlotinib have been widely clinical data includes: sex, age, pathological type, used in clinical treatment for superior clinical tumor stage, smoking history, Eastern Cooperative trial results at Stage III8. As the third single tar- Oncology Group Performance Status (ECOG-PS) get EGFR-TKI clinically applied to the treatment and chemotherapy history, etc. Before the treat- of advanced NSCLC, icotinib hydrochloride was ment, all patients were subjected to examinations the first Chinese small molecular targeted an- of blood routine, liver and kidney function, chest ti-cancer drug with the independent intellectual CT, abdominal color Doppler ultrasound, head property rights, and it is an effective and specific CT or MRI and bone scan (Thermo Fisher Scien- EGFR-TKI9. The basic research and clinical trial tific, Waltham, MA, USA) as well as evaluation suggested that icotinib hydrochloride and gefi- of ECOG PS score. The above indicators were tinib were similar in chemical structures, mole- checked regularly during the medication period, cular mechanisms, efficacies and other aspects; and the imaging examination was carried out after Phase III clinical trial, ICOGEN, proved equi- 1 month, then once in every 2 months until they valent clinical efficacy of both drugs in the se- had disease progression or adverse reactions for cond-line and third-line therapy of NSCLC, but intolerance. Among the 120 cases, there were 44 the icotinib hydrochloride was superior in safety females and 76 males, aged 44-80 (62.54±12.63) aspect8. Besides, a clinical observation indicated years old. For case stages, there were 41 cases of that the icotinib highlighted sounds efficacy and phase III B and 79 cases of phase IV. For tumor safety in treating advanced NSCLC patients. In types, there were 84 cases of adenocarcinoma, 27 this study, advanced NSCLC patients who have cases of squamous carcinoma, 6 cases of squamous complete clinical data upon treatment of icotinib adenocarcinoma and 3 cases of other types. By ran- hydrochloride or gefitinib from March 2010 to dom number table, all cases were evenly divided March 2016 were recruited to the retrospective into two groups, the experimental group (60 cases) analysis of efficacy, safety, and the exploration and the control group (60 cases). The process of of risk factors. patients’ recruitment and follow-up were shown in Figure 1. The study had been approved by Ethical Committee of Henan Tumor Hospital. All patients Patients and Methods had signed the informed consent. Inclusion criteria and exclusion criteria Methods The inclusion criteria: (1) Patients in pha- Patients in the experimental group orally took se III-B or IV NSCLC confirmed by histology icotinib hydrochloride (Beida Pharmaceutical Co., or cytology (according to the 7th Edition TNM Ltd, Hangzhou, Zhejiang, China) (H20110061, clinical staging criteria of NSCLC by IASLC); specification: 125 mg) three times a day and 125 (2) Patients with recurrence during or after the mg every time until they had disease progression first-line therapy; (3) At least one evaluable tar- or intolerance. Due to the side effects, 2 cases get lesion; (4) Aging between 18-80 years old; reduced dose to two times a day and 125 mg in (5) All patients have voluntarily signed the in- each time for one month, and after that they were formed consent. back in normal dose again. Patients in the control The exclusion criteria: (1) Lymphatic metasta- group orally took erlotinib (Roche Registration sis; (2) No evaluable lesion; (3) Other TKI taking Ltd, Welwyn Garden City, Hertfordshire, UK) history; (4) Radiotherapy and chemotherapy into- (H20120101) once a day and 100 mg in every day. lerance; (5) Using other drugs during medication During the treatment, patients received neither an- without permission; (6) With history of mental il- ti-tumor treatment except for important treatment lness, unable to cooperate with treatment, or being nor palliative radiotherapy except for the reason followed up; (7) Interstitial pneumonia; (8) The of releasing pain. patient’s last chemotherapy to this trial was less than three weeks, and still suffered from toxics Evaluation criteria and side effects with chemotherapy; (9) The life The Response Evaluation Criteria in Solid Tumor expectancy was less than 12 weeks; (10) Incom- (RECIST) was employed to evaluate the efficacy. plete clinical data. The first efficacy evaluation was performed in the 267 X.-H. Ma, T.-D. Tian, H.-M. Liu, Q.-J. Li, Q.-L. Gao, L. Li, B. Shi Figure 1. Patient recruitment and follow-up. fourth week after the medication, after which the ef- were analyzed by X2 test and Fisher exact test. ficacy evaluation was conducted every eight weeks Kaplan-Meier method was employed to carry out (less than one week between every two evaluable survival analysis and Log-Rank test for difference periods). The overall efficacy was divided into the significance. p<0.05 indicates statistical differen- complete response (CR), the partial response (PR), ce and p>0.05 indicates the opposite. the stable disease (SD) and the progressive disease (PD). The objective response rate (ORR) was calcu- lated by CR and PR, the disease control rate (DCR) Results was calculated by CR, PR and SD.
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