Interventional therapy for lung cancer patients with superior vena cava syndrome / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the method, therapeutic effect and safety of interventional therapy for lung cancer patients with superior vena cava syndrome (SVCS).</p><p><b>METHODS</b>Fifty-two cases of lung cancer with SVCS who received interventional therapy in our hospital between Jan to Dec 2011 were included in this study. Of the 52 cases, 50 cases had successfully carried out superior vena cava stent implantation. The distal venous pressure was measured before and after angioplasty, and the results were assessed by Wilcoxon matched-pairs test. In addition, the 50 patients were followed up and the therapeutic effect and postoperative survival rate were evaluated.</p><p><b>RESULTS</b>The mean distal venous pressure in the 50 patients was significantly decreased from preoperative (28.2 ± 1.9)cm H2O to postoperative (8.7 ± 0.5)cm H2O (P = 0.0085). The efficacy of the treatment was as follows: complete remission (20/52, 38.5%), partial remission (28/52, 53.8%), ineffective 4 (4/52, 7.7%), and total effective rate 92.3%. The complications after angioplasty and stent implantation included chest pain (12 cases, 23.1%), hematoma at the puncture site (5 cases, 9.6%), and fever (2 cases, 3.8%). No serious complications such as massive hemorrhage, pulmonary embolism and stent migration into the cardiac atrium were observed. The rate of postoperative restenosis was low (2/52, 3.8%). For the SCLC group, the objective effective rate was 74.1% and 1-year survival rate was 21.0%. For the NSCLC group, the objective effective rate was 21.7% and 1-year survival rate was 35.0%.</p><p><b>CONCLUSIONS</b>For lung cancer patients with SVCS, interventional therapy may relief obstruction effectively, promote blood flow recovery, and relieve clinical symptoms. Interventional therapy with endovascular angioplasty and stenting may be highly recommended as the first choice for palliative treatment of SVCS. It is an effective initial palliative treatment. However, subsequent comprehensive anti-tumor treatment is necessary.</p>

Correlation of CA-simple sequence repeat polymorphism of epidermal growth factor receptor gene with clinical outcome of patients with advanced non-small cell lung cancer after treatment with epidermal growth factor receptor tyrosine kinase inhibitors / 肿瘤

Objective: To investigate the correlation of CA-simple sequence repeat (SSR) polymorphismof epidermal growth factor receptor (EGFR ) gene with the clinical outcome of patients with advancednon-small cell lung cancer (NSCLC) after treatment with epidermal growth factor receptor tyrosinekinase inhibitors (EGFR-TKIs). Methods: The clinical outcome and the survival of 101 patients withadvanced NSCLC after treatment with EGFR-TKIs were measured. CA-SSR polymorphisim of EGFR intron1 from peripheral blood cells of NSCLC patients was detected by PCR and direct DNA sequencing. Thecorrelations of CA-SSR polymorphisim with the clinical outcome and the survival of NSCLC patientsafter treatment with EGFR-TKIs were analyzed. Results: Twenty-four patients reached a partial response(23.8%), 46 patients reached a stable disease (45.5%), and 70 patients reached a clinical benefit (69.3%).Median survival time (MST) in female or adenocarcinoma patients was longer than that in male or non-adenocarcinoma patients (P<0.05). Allele (CA)20 was the most frequent allele (68.7%, 68/99) in CA-SSR.Progression-free survival (PFS) in patients with short CA-SSR was longer than that in patients with long CA-SSR (P<0.039). The MSTs of patients with short CA-SSR and long CA-SSR were 15.7 and 14.4 months, respectively, and the difference in MST was not significant (P = 0.691). Conclusion: The MST of female or adenocarcinoma patients with NSCLC as well as the PSF of patients with short CA-SSR can be prolonged after treatment with EGFR-TKIs. Copyright© 2011 by Tumor.

Impact of erlotinib treatment on symptoms and quality of life in patients with advanced non-small-cell lung cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the impact of erlotinib as a second or third line treatment on the symptoms and quality of life (QOL) in patients with advanced non-small cell lung cancer (NSCLC).</p><p><b>METHODS</b>Fifty patients with stage III b and IV NSCLC, treated previously with at least one regimen of platinum-based chemotherapy, received 150 mg of erlotinib orally, once a day till disease progression. QOL was assessed by European Organization for Research and Treatment of Cancer QLQ-C30 and the lung cancer module (QLQ-LC13). The primary end points for QOL analysis were time to deterioration of three common lung cancer symptoms: cough, dyspnea and pain.</p><p><b>RESULTS</b>Among 47 evaluable cases, there were partial remission (PR) in 18 cases, stable disease (SD) in 21 cases, and progressive disease (PD) in 8 cases. After two cycles of treatment, the mean scores of global QOL and all 5 functioning scales except the cognitive function increased significantly (P < 0.05). Mean scores of major general symptoms, hypodynamia and anorexia, and disease-related symptoms alleviated significantly. Both response rates of five functioning and global QOL were more than 44% after erlotinib treatment. Response rates of major general symptoms and disease-related symptoms varied from 14% to 76%. Patients with complete or partial response likely had improvement in the QOL response (P < 0.05), and the time to major symptom deterioration in those were significantly longer (P < 0.001) than that in patients with stable or even progressive disease.</p><p><b>CONCLUSION</b>Erlotinib is effective to improve not only survival, but also tumor-related symptoms and quality of life in patients with advanced NSCLC previously treated with cisplatin-contained regimens. The improvement in the quality of life is positively correlated with objective tumor response.</p>

STI 571 potentiates the sensitivity of non-small cell lung cancer cell line A549 to cytotoxic effects of cisplatin in vitro / 肿瘤

Objective: This study was designed to compare the effects of STI 571 on proliferation, cell phases, and apoptosis between A549 and cisplatin-resistant A549 cells (A549/DDP) and detect the expressions of STI 571-related receptors in non-small cell lung cancer (NSCLC) tissues. Methods: A549 and cisplatin-resistant A549 cells (A549/DDP) were cultured in vitro. The cell proliferation was measured by MTT assay. Cell cycle distribution and apoptosis induced by STI 571, cisplatin and their combination were detected by flow cytometry in NSCLC cell lines. The expressions of platelet-derived growth factor receptor (PDGFRs) -α and-β and c-KIT in the non-small cell lung cancer cell lines and tissues were investigated by immunocytochemistry and immunchistochemistry, respectively. Kaplan-Meier survival curves were used to compare the correlation of PDGFR-α and-β expression with total survival of NSCLC patients. Results: STI 571 inhibited proliferation of A549/DDP cells, sensitized them to cisplatin chemotherapy, increased the cell number in G2/M and S phase, and induced apoptosis. However, STI 571 at the concentration below 10 μmol/L had no effect on the proliferation of A549 cells. Both A549 and A549/DDP cells expressed PDGFR-α and-β, but c-KIT expression was only observed in A549/DDP cells. The expression rates of PDGFR-α and-β were 65.5% and 69% in pulmonary adenocarcinoma, similar to those in squamous carcinoma (70.4% and 74.1%). Only one case of squamous carcinoma expressed c-Kit (3.7%). The PDGFR-α or β-positive patients had similar 3-year survival rates and overall survival time with the PDGFRα or β-negative patients. Conclusion: ST1 571 could suppress proliferation of A549/DDP cells, induce apoptosis and increase the sensitivity of A549/DDP to cisplatin. The levels of PDGFRα and β expression did not correlate with the prognosis of NSCLC patients.

Clinical study on the efficacy and safety of erlotinib in treatment of advanced non-small cell lung cancer / 肿瘤

Objective: To investigate the efficacy and adverse reaction of erlotinib as a single agent in 2nd and 3rd treatment of advanced non-small cell lung cancer (NSCLC) patients. Methods: Patients with advanced NSCLC (III B/IV stage) were recruited in this study. They had recurrence after receiving at least one or two regimens of platinum-based chemotherapy from October 2005 to September 2006. Erlotinib was given orally to the patients at 150 mg/d, once daily until disease progression. The clinical outcome and adverse reaction were observed. Patients were followed up. Kaplan-Meier method was used to perform survival analysis. Results: Fifty NSCLC patients were enrolled into the study and followed up until September 20, 2007. The median follow-up period was 17 months and the follow-up ratio was 100%. The clinical outcome could not be evaluated in 3 patients. There was no patient with complete response (0%, 0/47), 38.3% patients with partial response (18/47), 44.7% patients with stable disease (21/47) and 17.0% patients with progressive disease (8/47). Disease control rate was 83.0% (39/47). Median time to progression and median overall survival period were 7.0 and 13.7 months, respectively. One year progression-free survival rate and 1-year overall survival rate were 30% and 56%, respectively. Patients with II to III grade skin rash had higher response rate and disease control rate than those with 0 to I grade. The patients with partial response and stable disease obtained superior survival benefit than those with progressed disease. The occurence rate of skin rash over grade III was 4% (2/50). Conclusion: Erlotinib as a single agent is effective in the treatment of advanced NSCLC patients after failure of chemotherapy. The tolerance is well. The survival time is not dependent on gender, smoking status, and pathological classification. The patients with severe skin rash (> grade II) achieves better.

Detection of epidermal growth factor receptor mutations in non-small cell lung cancer by real-time PCR using TaqMan-MGB probes / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate mutations of EGFR TK gene in non-small cell lung cancer (NSCLC) and the diagnostic value of the mutations assayed by real-time PCR using TaqMan-MGB probes.</p><p><b>METHODS</b>Tyrosine kinase genes of EGFR (exons 18, 19 and 21) were amplified by PCR technology, and sequenced and analyzed by Chromas software in 80 NSCLC patients. Based on the results of sequencing, TaqMan-MGB probes were designed and used to detect the mutations of EGFR by real-time PCR. The results of detected mutations were compared between real-time PCR and direct sequencing. The sensitivity and specificity of real-time PCR using TaqMan-MGB probes were analyzed by adding different number of PC-9 cells (exon 19 deleted EGFR) into A549 cells (Wild-type EGFR).</p><p><b>RESULTS</b>Somatic mutations were identified in the tyrosine kinase domain of the EGFR gene in 21 of 80 NSCLC patients with an incidence rate of 26.3%. In-frame deletions of exon 19 occurred in 13 patients and point mutation occurred in codon 858 (exon 21) in 8 patients. Real-time PCR with the TaqMan MGB probes could detect all the mutations of EGFR found by sequencing. The sensitivity and specificity of the detection of EGFR mutations were both 100%. Real-time PCR with TagMan MGB probes could detect EGFR mutation in as rare as 50 EGFR mutant cells and in a proportion of 10% of mutant cells in a cell population. The mutations were significantly higher in the adenocarcinoma than in non-adenocarcinoma (16/38 vs. 5/42, chi2 = 9.702, P <0.01), in the female patients than in the male patients (14/29 vs. 7/51, chi2 = 11.4, P <0.01) and in non-smokers than in smokers (16/40 vs. 5/40, chi2 = 7.812, P < 0.01). The mutations were not related to patients'age, TNM staging, etc.</p><p><b>CONCLUSION</b>Somatic mutations of EGFR gene develop in NSCLC and are more common in female, non-smoker and adenocarcinoma patients. Real-time PCR using TaqMan-MGB, which can be used to detect the EGFR gene mutations, is easy to operate and deserves widespread application.</p>