Epidermal growth factor receptor genotype in plasma DNA and outcome of chemotherapy in the Chinese patients with advanced non-small cell lung cancer / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The genotype of epidermal growth factor receptor (EGFR) is associated with tyrosine kinase inhibitor and effectiveness of therapy, but its role in cytotoxic chemotherapy is still unknown. Previous studies indicated that certain EGFR mutations were associated with response and progression free survival following platinum based chemotherapy. Our recent studies have identified that EGFR genotypes in the tumour tissues were not associated with response to the first-line chemotherapy in Chinese patients with advanced non-small cell lung cancer (NSCLC). In this study, we investigated associations of EGFR genotypes from plasma of patients with advanced NSCLC and response to first-line chemotherapy and prognosis.</p><p><b>METHODS</b>We enrolled 145 advanced NSCLC patients who had received first-line chemotherapy in our department. We examined plasma EGFR genotypes for these patients and associations of EGFR mutations with response to chemotherapy and clinical outcomes.</p><p><b>RESULTS</b>There were 54 patients with known EGFR mutations and 91 cases of wild types. No significant difference was detected in the response rate to first-line chemotherapy between mutation carriers and wild-type patients (37.0% vs. 31.9%). The median survival time and 1-, 2-year survival rates were higher in mutation carriers than wild-types (24 months vs. 18 months, 85.7% vs. 65.7% and 43.7% vs. 25.9%, P = 0.047). Clinical stage (IV vs. IIIb), response to the first-line chemotherapy (partial vs. no) and EGFR genotype were independent prognostic factors.</p><p><b>CONCLUSION</b>Plasma EGFR mutations in the Chinese patients with advanced NSCLC is not a predictor for the response to first-line chemotherapy, but an independent prognostic factor indicating longer survival.</p>

Gefitinib in the treatment of advanced non-small cell lung cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the efficacy, time to progression, survival time and toxicity of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor Gefitinib (Iressa), a target therapy agent, in the treatment of advanced non-small cell lung cancer (NSCLC), and to analyze the factors affecting the efficacy and patients' survival.</p><p><b>METHODS</b>From Nov. 2003 to May 2005, 91 patients with advanced NSCLC who failed from previous first-line chemotherapy were treated by gefitinib in this trial with a median chemotherapy cycle of six. Sixty-eight of these 91 patients (74.7%) had received a second-line chemotherapy. Seventy-six (83.5%) of the 91 patients had stage IV disease, and 42 (46.2%) had developed metastases at least two sites. Gefitinib was administered orally at a dose of 250 mg daily until disease progressed or severe toxicity developed. Clinical data were analyzed using chi-square test, Log-lank test, Cox regression and Kaplan-Meier survival analysis in SPSS 11.5.</p><p><b>RESULTS</b>(1) Overall response rate was 20.9% (19/91) and the disease control rate (response and stable disease) was 63.7% (58/91). Patients'symptoms were improved in 72.7% (40/55), and ECOG score was improved or remained stable in 71.4% (65/91). The disease control rate of those who had adenocarcinoma, or received second-line chemotherapy or developed skin toxicity was significantly better than the other patients (P value = 0.04, 0.02, 0.00, respectively). (2) Median time to progress (TIP) was 5.0 months (95% CI 3.26-6.74). (3) Median following-up duration was 7.5 months (1-18. 5 months), and 1-year survival rate was 56.4%. Of the 56 patients (61.5%) who were still alive when following-up ended, 29 (51.8%) had stable disease, 20 had survived more than one year (12-18. 5 months). Non-smoker, stable diseases, skin toxicities, and controlled metastatic diseases during the treatment of gefitinib were the favorable factors affecting the survival (P value = 0.00, 0.00, 0.00, 0.01, respectively). (4) The main toxicity of gefitinib was grade I or II skin toxicity.</p><p><b>CONCLUSION</b>Gefitinib, a target therapy agent which may be an alternative, is effective and tolerable in the treatment for advanced NSCLC patients who have failed in the first-line or even second-line chemotherapy. It can remarkablely improve the disease control rate and disease-related symptoms, and also prolong survival in the responders.</p>

Phase II clinical trial on China manufactured recombinant human interleukin-11 derivative in the prevention and treatment of chemotherapy-induced thrombocytopenia / 中华肿瘤杂志

<p><b>OBJECTIVE</b>This phase II clinical trial was designed to evaluate the efficacy and toxicity of recombinant human interleukin-11 (rhIL-11) derivative manufactured in China in the prevention and treatment of chemotherapy-induced thrombocytopenia in cancer patients.</p><p><b>METHODS</b>A total of 100 cancer patients with chemotherapy-induced thrombocytopenia (< or = 75 x 10(9)/L) were studied by self-cross control. Ninty-one of them received 2 cycles of chemotherapy. In the first cycle (control cycle) the patients received chemotherapy only, while in the second cycle (treatment cycle), the patients were given subcutaneous injection of rhIL-11 derivative (40 microg.kg(-1).d(-1)) once daily after chemotherapy for 10 consecutive days or more until platelet count reached > or = 300 x 10(9)/L.</p><p><b>RESULTS</b>1. The patients with platelet count of < or = 75 x 10(9)/L was 89/89 in the control cycle and 44/89 in the treatment cycle (P = 0.00). The recovery time to the normal platelet count was 1-47 days (median 9 days) in the control cycle, and 1-18 days (median 5.5 days) in treatment cycle (P = 0.00). 2. Patients with platelet count of < or = 50 x 10(9)/L was 56/89 in the control cycle and 20/89 in the treatment cycle (P = 0.00). The recovery time to normal platelet count was 1-31 days (median 9 days) in the control cycle and 3-13 days (median 6 days) in the treatment cycle (P = 0.05). 3. The median nadir platelet count was 44 x 10(9)/L (range: 10 x 10(9)/L-75 x 10(9)/L) in the control cycle, and 83 x 10(9)/L (range: 10 x 10(9)/L-310 x 10(9)/L) in the treatment cycle (P = 0.00). The time of recovery to the normal platelet count was 1-31 days (median 6 days) in the control cycle, and 0-13 days (median 2 days) in the treatment cycle (P = 0.00). 4. Nine of 89 evaluable patients required platelet transfusion in the control cycle versus 1 of 89 patients in treatment cycle (P = 0.01), and the total platelet transfusion was 10 times in the control cycle versus once in the treatment cycle (P = 0.01). 5. The major adverse events associated with rhIL-11 derivative were: headache, fatigue, myalgia/arthralgia, edema and palpitation, etc.</p><p><b>CONCLUSION</b>rhIL-11 derivative can be safely and effectively used for the prevention and treatment for chemotherapy-induced thrombocytopenia.</p>

Plasma level and prognostic significance of VEGF, bFGF and MMP-9 in patients with advanced non-small-cell lung cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To measure plasma levels of VEGF, bFGF and MMP-9 in advanced non-small-cell lung cancer (NSCLC) patients and evaluate their prognostic value.</p><p><b>METHODS</b>The plasma levels of VEGF, bFGF and MMP-9 in 46 cases with advanced NSCLC were measured by ELISA before chemotherapy and in 30 cases after chemotherapy.</p><p><b>RESULTS</b>The plasma levels of VEGF, bFGF and MMP-9 in patients before chemotherapy were significantly higher than those in healthy control persons (P < 0.05). The correlation between plasma levels of VEGF and bFGF was significant, Spearman's r = 0.329 (P = 0.027). No correlation was found among the levels of angiogenic factors studied above and the following clinical parameters such as age, sex, histological subtype, differentiation of tumor cells, TNM-stage and also blood leukocyte, hemoglobin and platelet counts. The plasma level of MMP-9 in patients with extensive metastasis (including bone metastasis) was significantly higher than that in patients with bone metastasis only (P = 0.013). Reduction of plasma bFGF level after chemotherapy was a unique independent good prognostic factor (RR = 11.737, P = 0.02).</p><p><b>CONCLUSION</b>The measurement of plasma levels of such angiogenic factors as VEGF, bFGF and MMP-9 in advanced NSCLC is helpful for prediction of metastasis tendency and evaluation of prognosis.</p>