The Relationship Between Response To Platinum-based Regimens Chemotherapy And Genetic Polymorphisms Of DNA Repair Enzyme XRCC1 And The Effect On The Patients' Quality Of Life In Advanced Non-small Cell Lung Cancer

Background: Chemotherapy is the main treatment in advanced non-small cell lung cancer(NSCLC).Platinum-based of the two drugs combination is currently recognized standard first-line chemotherapy regimen, but the response is only about 30%, side effect also appear. It is necessary to be explored for predicting chemotheraputic response factor, so that we enable patients not only to get effective treatment and avoid side effects, but also to be helpful for individualized chemotherapy.Many factors affect the platinum-based chemotherapeutic effect including tumor cells resistance to chemotherapy and the individual inherent gene change related to chemotheraputic drug metabolism and damage repair. The DNA repair enzyme system polymorphisms play an important role on the response of platinum-based chemotherapy. It is possible to achieve chemotherapeutic response predictors to guide the development of clinical individualized chemotherapy by selecting detection of the DNA repair gene polymorphism loci. On the other hand, the effect of different platinum-based combination chemotherapy plus traditional Chinese medicine on patients chemotherputic response rate, survival time and quality of life is different in advanced non-small cell lung cancer, it is necessary to be explored and studied for these questions.Objective:To explore the relationship between genetic polymorphisms of DNA repair gene and response to platinum-based combination regimens chemotherapy in advanced non-small cell lung cancer. This study selects three standard first-line combination chemotherapy regimens (cisplatin plus NVB,GEM or PTX ) and detects patients DNA repair gene XRCC1 codon 399 polymorphism to observe the relationship between genetic polymorphisms and response to platinum-based combination regimens chemotherapy. Another, we compare difference of the short-term response and the progress free survival time (PFS ) in three combination chemotherputic regimens and observe the effect of chemotherapy or combination with traditional Chinese medicine on patients quality of life.Methods: 64 patients with advanced non-small cell lung cancer diagnosed by pathology and in accord with the standard of research scheme were admitted and randomized to different research scheme including different chemotherputic regimens and chemotherapy alone or chemotherapy plus traditional Chinese medicine. All patients' DNA of peripheral blood leukocytes was obtained before therapy. Taqman probe were used to analyze the SNP of XRCC1 codon399 and genotypes were detected by Stratagene soft .The short-term response were evaluated by Response Evaluation Criteria in Solid Tumors after 2 to 4 courses chemotherapy, and then the correlation of genotypes polymorphisms to clinical response analyzed. The progress free survival time (PFS) was evaluated by follow-up, the effect of chemotherapy alone or chemotherapy plus traditional Chinese medicine on the patient's quality of life were understood by questionnaire before and after therapy.Results:1) The genotypes distribution of XRCC1 codon 399 were Arg/Arg 2( 3.1%),Arg/Gln 60(93.8%) and Gln/Gln 2(3.1%).2) The response rate to chemotherapy among patients with Arg/Arg,Arg/Gln and Gln/Gln genotype was 100%, 32.6% and 0.3) The overall response rate to platinum-based chemotherapy in all of 64 patients'was 32.8%. The short-term response rate of the NP,GP,TP groups was 28%,40%,29.4% and the PFS of NP group was 15.1 weeks, 25.6 weeks in GP group and 13.1 weeks in TP group.4) Analyzed by QLQ-C30: All the patients after chemotherapy the score of physical function, the role function and global health status were increased (P<0.05); the score of symptoms - fatigue,pain,dyspnea,insomnia,anorexia were decreased (P <0.05); and there is no significant change in cognitive function,social function constipation,and diarrhea etc.5) The response rate of the chemotherapy plus traditional Chinese medicineand chemotherapy alone was 14 (37.84%) and 7(25.93%), there were no statistical difference (P>0.05) in the response rate and side effect. Comparing chemotherapy alone group with chemotherapy plus traditional Chinese medicine group, the former′s score of QLQ-C30 in emotional, fatigue, nausea and vomiting, dyspnea,insomnia, anorexia improved more significantly than the later′s (P<0.05) after chemotherapy. Chemotherapy plus traditional chinese medicine also improved symptoms of cough, increased weight and KPS (>10).Conclusion:1) In our study, the genotype of DNA repair gene XRCC1 399 is mainly distributed to Arg/Gln. Arg/Arg and Gln/Gln genotype appeared only in few cases.2) As the fewer cases distribution of Arg/Arg,Gln/Gln genotypes, it is impossible to contrast the relationship of chemotherapy response to genotype. However, we preliminary found Arg/Arg genotype more sensitive to platinum-based chemotherapy than Arg/Gln and Gln/Gln genotypes.3) Chemotherapy can improve the patient's quality of life in advanced non-small cell lung cancer. 4) There is no significant different in response rate and PFS among these three groups chemotherapy scheme. The patients response to chemotherapy in three groups were significantly improved in the quality of life.5) Chemotherapy plus traditional Chinese medicine group and the chemotherapy alone group have no significant difference in the response to theraputy, but the former is more obviously in increasing the quality of life and improving symptoms.