| 1 Background and purposeLung cancer is the leading cause of cancer related death. Smoking, environmental pollution etc. are major factors attributing to the development of carcinoma. The non-small cell lung cancer (NSCLC) is the major pathological type of lung cancer (85%) with 5-year survival rate less than 15%. Mounting researches show that the advanced cancer from precancerous lesions or early stage carcinoma loses its curable opportunity with 5-year survival rate of 4.2% for lacking an effective screening methods.The EGFR (epidermal growth factor receptor) family consists of 4 closely related receptors, HER-1/ErbB1, HER-2/neu/ErbB2, HER-3/ErbB3 and HER-4/ErbB4 with significant homology in their kinase domains, but differences in the coding regions for the extracellular domain and the C-terminal tails. It is a 170-kDa plasma membrane glycoprotein consisting of a large extracellular region, a single transmembrane domain, and an intracellular domain with tyrosine kinase activity and a C-terminal tail. Activation of the EGFR receptor via phosphorylation relays downstream signals to the phosphatidylinositol 3-kinase (PI3K)/AKT and RAS/RAF/mitogen-activated protein kinase (MAPK) pathways. These intracellular signaling pathways are responsible for the normal regulation of essential cellular processes such as proliferation, differentiation and apoptosis. EGFR-TKIS (epidermal growth factor receptor-tyrosine kinase inhibitors) induce non-active dimerization by competing with ATP receptor reversibility, inhibiting EGFR kinase activity and resulting in cell cycle arrest, apoptosis, anti-angiogenesis, and growth inhibition.Mutations in the EGFR gene occurring in NSCLC are commonly localized within the tyrosine kinase domain of the gene, which promotes the conjunction stability with mutation site and EGFR-TKIS increasingly. Well established mutations include sensitive mutations and resistant mutations. Mutations in exions 18,19, and 21 consist of the sensitive mutations and exion 20 is the resistant mutation. The proptions of exion 18,19,20,21 are 4.7%,44%,9.3%,42% respectively. Activating mutations in the gene encoding the EGFR protein are present in approximately 10-20% of NSCLC patients diagnosed in North America and Western Europe and 30-50% of Asian patients. Other studies show that the active rate of EGFR gene mutation in Chinese NSCLC patients is about 30% in unselected patients,50% in patients with adenocarcinoma,60-70% in non-smoking patients with lung adenocarcinoma and 10% in squamous cell lung carcinoma.Currently the EGFR-TKIS are categorized as follows:the first generation: gefitinib, erlotinib, icotinib; the second generation:afatinib, dacomitinib; the third generation:AZD9291, CO 1686, HM61713. The first generation of molecular targeted drugs are beneficial to patients of lung cancer with EGFR sensitive mutations mostly in terms of PFS, but there are some other people with bad PFS. So this article will focus on the efficacy of three EGFR-TKIS of the first generation, such as gefitinib, elotinib and icotinib, in NSCLC patients with EGFR sensitive mutations.2 Methods(1) We retrospectively followed up 95 cases of advanced NSCLC patients with EGFR sensitive mutations (exon 19 deletion vs L858R in exon 21) according to the including standards. All patients received first-line gefitinib 0.25mg qd (33 cases), erlotinib 0.15mg qd (32 cases), icotinib 125mg tid (30 cases) respectively until disease progression or intolerable drug related adverse events.(2) Between November 1,2013 to 30th December 2013, the test of peripheral blood EGFR was applied to 21 outpatients of lung cancer in our hospital, who received no prior chemotherapy, radiotherapy and biological therapy with a confirmed EGFR mutation status or tumor tissues).(3) The χ2 test of R*C was used to compare the difference of ORR (objective response rate) and DCR (disease control rate). Kaplan-Meier (Log-rank) was applied to compare the PFS (progression free survival) among groups and Cox regression analysis was used to explore prognostic factors on PFS. P<0.05 was identified as significant statistical.3 Results(1) The ORR, DCR, median PFS of three EGFR-TKIS were 63.3% vs 71.9% vs 60.0%(P=0.600),90.9% vs 93.8% vs 93.3%(P=0.894),346 days vs 390 days vs 386 days (P=0.497). Meanwhile, the Cox regression analysis showed that tumor differentiation was an independent prognostic factor for PFS.(2) No significant difference was observed in exon 19 vs 21 EGFR sensitive mutation patients. However, patients with exon 19 EGFR mutation have a tendency to benefit from EGFR-TKIS compared with patients of exon 21 EGFR mutation (472 days vs 328 days, P=0.116).(3) The specificity and sensitivity of peripheral blood EGFR was 90.9%(10/11 patients),70%(7/10 cases) respectively compared with tumor EGFR test. The EGFR concordance of peripheral blood and tumor was 81.0%(17/21).4 ConclusionsThe first-line gefitinib, erlotinib and icotinib benefit equally in NSCLC patients with EGFR sensitive mutations. Both exon 19 deletion and L858R in exon 21 mutations can benefit from EGFR-TKIS therapy.1 Background and purposeThe toll death number of lung cancer in China has increased continously by 465% since 1980s according to the China Lung Cancer Summit in 2013. It was estimated that the patients of lung cancer in China would rank as the most in the world by 2025. People living with advanced cancer are a diverse population that are newly diagnosed or diagnosed with recurrent disease by pathologists, are receiving active anticancer treatment, are in the end stage of their life. Virnig et al. reported that up to 42% of patients with lung cancer are diagnosed to have metastatic disease with poor prognosis.Comparing to those patients of early stage or localized disease, people with advanced cancer often suffer much more physical, emotional, and spiritual disorders. Physical symptoms contain pain, dyspnea, constipation, fatigue and sleep pattern disturbances. Emotional symptoms involve anxiety, depression, and grief for actual or potential losses.The expressions of existential distress, loss of meaning, the need for forgiveness and isolation from family, friends, community and religious are spiritual symptoms. It was reported that anxiety is common in cancer patients (12%) and depression in advanced cancer patients shows higher morbility (56%-77%) respectively, which impaire the patients’treatment compliance, will to live, quality of life, increasing the disease mortality, weakening the roles of social and family and resulting in huge medical costs. Furthermore, it was found that 60% of family members of cancer patients have major life changes and 25% patients report difficulty in functioning normally. Family members of patients with cancer may experience poorer physical, psychological, and poorer social functioning than family members of patients with other chronic diseases. This is mainly attributed to the caregiver pressure which originates not only from regular life of caring patients, such as eating, sleeping moderate exercise, etc., but also participating the patients’ decision-making of treatments combined the patients’ will, the familiar belief and economy. All these factors containing physical, psychological, emotional and social problems promote the unpleasant sense to caregivers. Moreover, it was concluded that the severity of depression in patients is positively related to that of family members. The older, women, religious or patients received radical operation suffer higher incidence of depression.The EGFR-TKIS were administrated to NSCLC patients haboring EGFR sensitive mutations with high response rate and tolerable toxic effects. However, the platinum-based doublet-agents were chosed as the standard first line regimen for the EGFR wild-type NSCLC patients with benefit. Meanwhile, the complications of chemotherapy including digestive tract reaction, hematologic toxicity, liver and kidney toxicity, alopecia, chemobrain, etc. reduced quality of life (QOL). The previous clinical trials demonstrated that depression and anxiety had an association with health related QOL. Patients with depression showed a worse median overall survival and poor treatment adherence. Moreover, the better QOL scores, the longer the survival. Therefore, chemotherapy may deteriorate patients’ anxiety and depression.The previous study showed that the treatment of CBI on cancer patients alleviated anxiety and depression, feeling of social support, self-efficacy and QOL. The CBI is guided by psychology, behavioral science and education including social learning theory, self-efficacy theory, adult education, and stress and coping theory, to relieve symptoms and foster the ability to cope questions. Cognitive, behavioral and educational are identified as the three major types of interventions. The detail mechanism of cognitive interventions contains the identification and modification of negative thoughts, beliefs and expectations, including cognitive restructuring, problem solving, guided imagery, and meaning-making interventions. Behavioral interventions are aimed to increase the use of adaptive behaviors instead of maladaptive behaviorsand behavior learning based on rewards and punishments. Pyscho-educational interventions have been an effective methods in the relief of physical and emotional symptoms in cancer patients.So far, it is unclearly how the combined treatment regimenes of CBI intervention on patients and caregivers affect advanced cancer patients. This article will draw on it specifically. 2 Methods2.1 According to the study including criteria,100 cases of advanced lung cancer patients receiving first-line chemotherapy (stage IIIB or IV) were allocated randomly to 4 groups:the first group received CBI in patients and caregivers of advanced lung cancer, the second group accepted the CBI in patients of advanced lung cancer only, the third group received CBI in the caregivers of advanced lung cancer only, and the fourth group was a controled group with no CBI. The intervention was lasted for four weeks using self-rating anxiety scale (SAS), self-rating depression scale (SDS). The difference of SAS (SAS1-SAS2) and SDS (SDS1-SDS2) before and after the intervention were calculated respectively.2.2 The SAS difference (SAS1-SAS2) and SDS difference (SDS1-SDS2) before and after intervention in 4 groups were analyzed by completely random design analysis of variance or chi-square test. 3 Results3.1 The anxiety and depression were found in 56% and 57% patients of advanced lung cancer patients, and the anxiety and depression of caregivers were observed in 25%,18% respectively. Moreover, patients who are women, youth, PS=2, the smoking index≥400, suffering complications and sleeping disorders tended to be anxiery and patients who are women, youth, PS=2, suffering complications and sleeping disorders tended to be depression. The caregivers of patients who are women and youth tended to be anxiery and people who are women, youth and sleeping disorders tended to be depression.3.2 A statistical difference of cancer patients in SAS and SDS before and after CBI in each group was significant (P<0.05). Furthermore, subgroup analysis revealed that the SAS and SDS of first group were significantly higher than the other three groups (P<0.05). No significantly statistical difference was found between group 2 and 3 (P<0.05). 4 ConclusionsCBI is an effective approach that can improve patients’mood with advanced lung cancer during first-line chemotherapy obviously. |
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