[Detection of epidermal growth factor receptor gene mutations in advanced non-small cell lung cancer].

OBJECTIVE: To investigate the mutations of epidermal growth factor receptor (EGFR) in tumor tissue and pleural effusion in advanced non-small cell lung cancer (NSCLC) patients, and to analyze the relationship between EGFR mutations and the clinicopathologic characteristics. METHODS: Two-hundred and forty-one cases of formalin-fixed, paraffin-embedded tumor tissues and 14 paired pleural effusions from advanced NSCLC patients were collected. Twenty-nine different EGFR mutations in exons 18-21 were assessed by scorpions and amplification refractory mutation system (scorpions ARMS) using real time PCR. The relationship between the EGFR mutations and clinical parameters was analyzed using statistical methods. EGFR mutation of 37 cases were detected with direct sequencing, and assessed the sensitivity, the specificity and the accuracy of scorpions ARMS. RESULTS: EGFR somatic mutations were detected in 114 of 234 advanced NSCLC patients, with the mutation rate of 48.7%, including deletions in exon 19 in 65 patients and point mutation of L858R in exon 21 in 39 patients; both accounting for 91.2% (104/114) of all types of EGFR mutations. The test results of 14 paired pleural effusion specimens were entirely the same to the tissues. The concordance rate of 2 different detection methods was 94.6%. Mutation rate was higher in women (55.9%) than in men (42.2%), and there was no difference in mutation rates between smokers and non-smokers; patients in stage IIIB and stage IV; adenocarcinoma and non-adenocarcinoma. CONCLUSIONS: EGFR somatic mutations appear to occur frequently in Chinese. Scorpions ARMS technology is a sensitive method to detect EGFR mutations and is suitable for screening patients who would likely respond to EGFR inhibitors therapy.

[Efficacy analysis of third-generation plus platinum doublets in the first-line chemotherapy of advanced non-small cell lung cancer].

OBJECTIVE: To compare the chemotherapeutic efficacies of third-generation plus platinum doublets in advanced non-small cell lung cancer (NSCLC) patients. METHODS: A total of 1112 patients were diagnosed as advanced NSCLC at Chinese Academy of Medical Science and Cancer Hospital from January 2005 to August 2009. Their clinical efficacies and regimen compositions were retrospectively analyzed. All calculations were performed by SPSS 17.0. RESULTS: Differences in objective response rate (ORR) existed among four third-generation agents (paclitaxel, gemcitabine, vinorelbine and docetaxel) plus platinum doublets. Their ORRs were 35.6%, 35.4%, 25.9% and 37.4% respectively (χ(2) = 16.331, P = 0.001). And vinorelbine doublets had the lowest ORR (all P < 0.01). The ORRs of cisplatin and carboplatin doublets were 35.2% and 33.5% respectively. There was no difference in ORR among them (χ(2) = 0.352, P = 0.569). Subgroup analysis showed that the ORRs of four third generation plus platinum doublets were 34.8%, 35.3%, 23.2% and 37.1% in non-agers. And the vinorelbine doublets performed the worst. In the patients with squamous-cell lung cancer, the ORRs of paclitaxel and gemcitabine doublets were 45.5% and 28.4% respectively. And the paclitaxel doublets had the better performance (χ(2) = 5.250, P = 0.026). When combined with carboplatin, the ORRs of four doublets were 36.2%, 16.7%, 15.4% and 32.0% respectively. And the paclitaxel regimen was more effective than the gemcitabine and vinorelbine regimens (P = 0.018 and P = 0.034). The influences of subsequent therapy were nullified when the progression-free survival (PFS) was analyzed. The PFSs of these doublets were (3.67 ± 0.19), (2.95 ± 0.18), (3.05 ± 0.36) and (3.40 ± 0.37) months respectively. There was no difference among them. Pairwise comparisons showed that the mean PFS of patients on paclitaxel doublets was longer than those on gemcitabine doublets. And their PFSs were (3.67 ± 0.19) and (2.95 ± 0.18) months respectively (χ(2) = 7.037, P = 0.008). The PFSs of cisplatin and carboplatin doublets were (3.05 ± 0.14) and (3.65 ± 0.20) months respectively. The patients on carboplatin doublets had a longer PFS than that of those on cisplatin doublets (χ(2) = 6.012, P = 0.014). CONCLUSIONS: No difference exist in ORRs among different third-generation plus platinum doublets. But as the first-line treatment of advanced NSCLC, carboplatin doublets is superior to cisplatin doublets in terms of PFS.

[Factors affecting the sensitivity of EGFR-TKI treatment in advanced non-small cell lung cancer].

OBJECTIVE: To explore the clinical factors affecting the sensitivity of EGFR-TKI treatment in advanced non-small cell lung cancer. METHODS: Clinical data were retrospective analyzed to determine the clinical factors affecting the outcome of 166 patients with advanced non-small cell lung cancer who received EGFR-TKI treatment in our hospttal from January of 2005 to December of 2006. RESULTS: One hundred and nineteen patients benefited from EGFR-TKI treatment in the total of 166 patients and the disease control rate was 71.7%. Among the factors analyzed, sex, age, smoking, pathological type, brain and bone metastasis or not when EGFR-TKI was used, the time using EGFR-TKI and the level of LDH at the time of diagnosis had no significant effect on the clinical benefit rate. Among the 126 patients with serum CEA assayed at diagnosis, 84 cases had a higher serum CEA level. Compared with the patients with normal serum CEA level, the patients with a higher serum CEA level benefited more easily from EGFR-TKI therapy, with a disease control rate of 79.8% and 59.5%, respectively (P = 0.016). Among the patients who got benefits from EGFR-TKI treatment, smoking and the CEA level at diagnosis had effects on the duration of progression-free survival. The progression free survivals were 9.57 ± 6.75 months in non-smokers, 4.86 ± 3.44 months in light-smokers and 5.25 ± 4.34 months in heavy-smokers (P = 0.007). The progression free survival was 9.45 ± 7.48 months in the group with a higher serum CEA level and 6.52 ± 4.46 months in the group with normal serum CEA level (P = 0.036). CONCLUSIONS: In patients with advanced non-small cell lung cancer, EGFR-TKIs treatment is safe and effective. The patients with high CEA level are prone to benefit from it.

[Analysis of chemotherapeutic efficacy after a failed regimen of epidermal growth factor receptor-tyrosine kinase inhibitor in patients with advanced non-small cell lung carcinoma].

OBJECTIVE: To analyze the treatment efficacy after a failed regimen of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) in patients with advanced non-small cell lung carcinoma (NSCLC). METHODS: A retrospective analysis was conducted for 87 patients with advanced NSCLC at our hospital from January of 2005 to December of 2006. All subjects received chemotherapy after a failure of EGFR-TKI, there were 37 cases of male and the median age was 56 ± 11 (range, 31 - 76) years, 50 cases of female, median age 56 ± 13 (range, 31 - 78) years; They received a 2-drug combination chemotherapy (n = 61) and a monodrug chemotherapy (n = 26). The primary endpoint was overall survival (OS). And the secondary endpoints were objective response rate (ORR) and side effects. RESULTS: The OS was 9.4 ± 6.0 (range, 2-33) months and ORR 9.2% (8/87). The OS was 9.1 ± 5.2 (range, 2 - 31) months in combination chemotherapy group and 10.0 ± 7.3 (range, 3 - 33) months in monodrug group; the ORRs were 11.5% (7/61) and 3.8% (1/26) respectively in two groups. There was no significant difference in OS and ORR between two groups (P > 0.05). The common side effects were myelosuppression and nausea/vomiting. The rate of myelosuppression was 87.4% (76/87) and that of 3/4 grade myelosuppression 33.3% (29/87). And the rate of nausea/vomiting was 86.2% (75/87) and that of 3/4 grade nausea/vomiting 10.3% (9/87). Other side effects were mild and well-tolerated. CONCLUSION: If tolerated, chemotherapy after an EGFR-TKI failure may prolong the survival in advanced NSCLC patients.