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Objective To observe the short-term efficacy and safety of sequential administration of erlotinib and chemotherapy in unselected, chemonaive patients with advanced non-small-cell lung cancer (NSCLC). Methods Previously-untreated patients (n=23) with stage Ⅲ_B/Ⅳ NSCLC and ECOG PS of 0/1 received erlotinib (150 mg/d) on days 15-28 of a 4-week cycle that included gemcitabine (1250 mg/m~2, days 1 and 8), and either cisplatin (75 mg/m~2, day 1) or carboplatin (AUC=5, day 1). The primary end points were tumor response rate and safety. Results 23 patients received a total of 95 cycles of treatment, and all were evaluable for efficacy and toxicity. The overall response rate was 30.4%, 0 case achieved complete responses (CR), 7 cases (30.4%) achieved partial responses (PR), 14 cases (60.9 %) achieved stable disease (SD), 2 cases (8.7 %) achieved progression disease (PD). The disease control rate was 91.3 %. The sequential administration of erlotinib following gemcitabine/platinum chemotherapy was well tolerated. The major grade 3 treatment-related adverse events were eutropenia (13.4%), rash (8.7%), nausea (8.7%) and thrombocytopenia (8.7%). No treatment-related interstitial lung disease. Conclusion equential administration of erlotinib following gemcitabine/platinum chemotherapy was effective, and the toxicity was tolerable. This treatment strategy warrants further investigation.
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<p><b>BACKGROUND</b>Dendritic cell (DC)-based immunotherapy is a new approach and effective for some malignant tumors. The aim of this study is to observe the efficacy and toxicity of immunotherapy with carcinoembryonic antigen (CEA) peptide-pulsed DCs in patients with refractory advanced lung cancer.</p><p><b>METHODS</b>Lung cancer patients with high CEA expression were enrolled into this project. Autologous DCs were generated from patients' plastic-adherent peripheral blood mononuclear cells and loaded with CEA 5 days later. Cytokine-induced killer cells (CIK) were cultured from non-adherent peripheral blood mononuclear cells. DCs and CIK were transfused to patients. Responses and toxicities were observed.</p><p><b>RESULTS</b>A total of 22 patients with lung cancer received DCs immunotherapy. DCs doses were 2.5×10⁶-9.6×10⁷ (5.03×10⁶). CIK doses were 3.4×10⁸-46×10⁸. CD3, CD8, NK and IFN-γ levels obviously increased after treatment (P < 0.05). The 1-year survival rate was 68.2% (15/22). Main toxicities were fever and rash.</p><p><b>CONCLUSIONS</b>DCs-based immunotherapy is feasible and safe to patients with lung cancer.</p>
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For advanced lung cancer,multimodality treatment is the main stream.Patients with locally advanced disease may have long-term survival rate with radiation therapy combined with chemotherapy.Patients with advanced metastatic disease may achieve improved survival and palliation of symptoms with chemotherapy.Here we reviewed the recent development in treatment for advanced non-small cell lung cancer.
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The clinical evidences of the guideline came from clinical trials based evidence-based medicine. Applied principle of the evidence was: systematic reviews, RCTs, the results from multiple factors ana-lysis, consensus, especially combined with Chinese experience and some lung cancer guidelines used in USA or Europe. All doctors who use the guideline in making therapeutic strategy must combine patients' conditions with the knowledge of biological behavior, dynamic change and response to treatment of lung cancer.
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<p><b>BACKGROUND</b>To compare the effect and toxicity between gemcitabine and cisplatin (GP) with vinorelbine, ifosfamide and cisplatin (NIP) combined chemotherapy in the treatment of patients with advanced non-small cell lung cancer (NSCLC).</p><p><b>METHODS</b>Eighty patients received either gemcitabine 1 000 mg/m² on days 1, 8, or 15 plus cisplatin 70-80 mg/m² on day 1, or vinorelbine 25 mg/m² on days 1, 8, ifosfamide 1.2 g/m² on days 1-4 plus cisplatin 70-80 mg/m² on day 1, every 28 days as a cycle.</p><p><b>RESULTS</b>The objective response rate was 40.0% in GP goup, compared with 52.5% in NIP group (P > 0.05). Median survival time of GP and NIP groups was 13.68 and 15.34 months respectively, and 1-year survival rates were 54.29% and 59.46% respectively (P > 0.05). Leukopenia at grade III+IV was significantly lower in GP arm (27.5%) than that in NIP arm (55.0%) (P < 0.05). Non-hematological toxicities were less frequent in GP group than those in NIP group (P < 0.05).</p><p><b>CONCLUSIONS</b>Although the response rate tends to be higher in three-drug than in two-drug combined chemotherapy, but no significant difference is observed. Three-drug combinations often result in more toxicities. Two-drug combination GP may be the standard protocol for chemotherapy of advanced NSCLC. Three-drug combination NIP should be given to young patients with good performance status.</p>
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<p><b>BACKGROUND</b>To determine the value of preoperative cardiopulmonary risk index (CPRI) in predicting the short-term prognosis after lung resection in patients with lung cancer.</p><p><b>METHODS</b>Preoperative clinical data were used to generate a cardiac risk index (CRI) and a pulmonary risk index (PRI). And the value of cardiopulmonary risk index (CPRI) consisting of CRI and PRI in predicting postoperative prognosis was estimated in patients who underwent lung resection at Shanghai Chest Hospital in 1999.</p><p><b>RESULTS</b>A total of 625 consecutive patients were studied. Postoperative complications occurred in 49 patients (7.8%), including 8 deaths within 30 days of operation. In the total group, CRI, PRI and CPRI scores ranged from 1 to 3, 0 to 5 and 1 to 7, respectively. There were 489 patients with CPRI < 4, and 136 with CPRI≥4. Using CPRI≥4 as a threshold for predicting postoperative complications, the sensitivity, specificity and accuracy rate were 75.5%, 82.8% and 82.2% respectively.</p><p><b>CONCLUSIONS</b>The preoperative CPRI is one of the important indexes in predicting the short-term postoperative prognosis for patients with lung cancer. However, it can not completely predict all of postoperative risks, and should be used together with other factors.</p>
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<p><b>BACKGROUND</b>To detect dendritic cells (DC)in the peripheral blood and plasma concentration of vascular endothelial growth factor (VEGF) of patients with non-small cell lung cancer (NSCLC) and to evaluate their relationship.</p><p><b>METHODS</b>The quantitation of DC in the blood was performed in 55 patients with NSCLC, 13 patients with pulmonary benign diseases, and 12 healthy volunteers by a novel flow cytometric assay. The concentration of VEGF in the plasma was measured by ELISA kit.</p><p><b>RESULTS</b>No significant difference was found in the levels of DC and VEGF between the patients with pulmonary benign diseases and healthy volunteers (P>0.05). In comparison with subjects of healthy volunteers and pulmonary benign diseases, the level of DC was significantly decreased, while that of VEGF was significantly increased in the patients with NSCLC(P < 0.05 to 0.01). The levels of DC and VEGF in the peripheral blood of NSCLC were closely associated with TNM stages and lymph node metastasis. However, no correlation was found among the levels of DC and VEGF and age, gender, cell differentiation and histologic classification. There was a negative correlation between the VEGF concentration and the DC counts.</p><p><b>CONCLUSIONS</b>The decline of DC count in peripheral blood and the enhancement of plasma VEGF are remarkably related to the malignancy of NSCLC. And VEGF overexpression may be one of mechanisms of DC maturation and differentiation inhibition in patients with NSCLC.</p>
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Background and Purpose:Lung cancer is the most malignant tumour in the world.Its incidence is growing and NSCLC is predominent(80%) in lung cancer.Most patients with lung cancer were diagnosed in late stages.The tumour could be shrunk by neoadjuvant chemotherapy when the case with stage Ⅲ NSCLC was considered not possible for radical operated neoadjuvant chemotherapy may lead to the following,operation could be improved,micrometastasis could be annihilated and survival could be extended.Objective of this paper was to analyse the prognostic factors for survival in patients treated by surgery and chemotherapy for NSCLC.Methods:98 cases of neoadjuvant chemotherapy combined with surgery for NSCLC,stageⅠ~Ⅲ,were collected retrospectively in our hospital from 1995 to 1997.35 cases were stageⅠ.21 cases were stage Ⅱ.42 cases were stage Ⅲ.83 cases had 1 cycle of chemotherapy pre-operatively.15 cases had 2 cycles chemotherapy pre-operatively.Regimes of chemotherapy were MVP,MOP and MAP et al.Response rate(RR) of chemotherapy was:45 cases had partial response(PR) and 53 cases were stable disease(SD).Operative mode was lobectomy and pneumectomy with lymph nodes dissection.Pathologic type was squamous,adeno,adeno-squamous and others.All the patients were treated by chemotherapy for two or three cycles after surgery except for the patients in stageⅠin 1996~1997.After being followed-up for more than 5 years,data were examined using life table,KaplanMeier method,Log Rank statistic and Cox-mantel test.The possible factors affecting survival were tested with univariate and multivariate analysis.Results:The median followed-up time of 98 cases for NSCLC was 41.2 months.36 cases were alive.62 cases were dead.The 1-,3-,5-year survival rate of 98 cases for NSCLC was 88.78%、49.63% and 18.46%.The 5-year survival rates of stageⅠ、ⅡandⅢ were 33.23%、20.26% and 5.52% respectively(P=0.0002).The 5-year survival rates of N_(0)、N_(1)、N_(2) were 35.49%、19.08% and 4.90% respectively(P=0.0004).In the 98 cases of NSCLC,better prognosis was correlated with earlier stage.The prognosis was better if the period from last chemotherapy before operation to operation was no more than 1 month. The prognosis of lobectomy,lung hila activity,thorax lymph nodes negativity and squamous cancer was better.The prognosis was poorer if the tumor had invaded big vessels,viscera,chest wall,pericardium and quantity bleeding during≥400ml.The prognosis was better if the tumor was fibrotic.The prognosis of 2 cycles of chemotherapy pre-operatively might be better than 1 cycle.The prognosis of tumor necrosis was poorer and the prognosis of chemotherapy post-operatively was better.Conclusions:The main prognostic factors affecting survival in patients treated by surgery and chemotherapy for NSCLC was stage,the period from last chemotherapy before operation to operation,operation mode,lung hila activity,thorax lymph nodes,site of tumor invasion,bleeding quantity,pathologic type,tumor fibrosis and necrotis,cycles chemotherapy pro-operation and chemotherapy post-operation.
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Purpose:To evaluate the effect of cisplatin-based peri-operation chemotherapy (CT) on survival after completed resection of non small cell lung cancer (NSCLC)Methods:A prospective, randomized, multicenter study was conducted by Shanghai Lung Cancer Team since Feb 1995 to Dec 2003 for stage Ⅰ~ⅢA NSCLC with completed resection. Patients were randomly assigned to receive pre-operative CT or no pre-operative CT (pre-op CT). Post-operative CT (post-op CT) were used for majority of the patients, except for partial stage I patients. Accumulated survival, log rank, MST, Cox uni-variance and multi-variance analyses, HR were used as statistics for evaluation Results:A total of 337 patients underwent randomization, 169 cases received pre-operative CT, and 168 cases didn't receive pre-operative CT. There was statistical survival difference between the group with no pre-op CT and with pre-op CT, 5-yr survival rate were of 47.85%∶ 36.52%, MST were 56.63∶39.14(P=0.03), respectively. Stage and post-op CT were the only two meaningful parameters with statistical survival difference calculated by multi-variance analyses (P0.05). There were 121 cases received more than 3 cycles post-op CT, 216 cases received less than 3 cycles post-op CT. The patients received more than 3 cycles had better yr-survival and MST than those received less cycles (P=0.04).Post-op CT was not benefit to the survival rate of stage I. In stage Ⅱ and ⅢA ,the patients received ≥3 cycles post-op CT had better yr-survival than those received less cycles(P
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Purpose:To evaluate the effects of thymosin ?1 (T?1) in chemotherapy of NSCLC. Methods:We have conducted a prospective randomized controlled clinical trial.40 non-treated cases of stage Ⅲ-Ⅳ NSCLC were randomized into T?1 group ( chemotherapy combined with thymosin ?1) and control group (chemotherapy alone). The number of T cell subgroups, the activity of NK cell and phagocytic index of neutrophilic granulocyte in peripheral blood were detected and quality of life and changes of cancer lesions were evaluated before and after treatment. Results:After treatment,the levels of CD4 in the T?1 group was significantly higher than before treatment(P0.05). There was no significant difference of myelosuppression between the two groups. No infections or severe toxicity occurred in the T?1 group. One severe lung infection was seen in the control group.There was better quality of life for the T?1 group compared with the control group(P
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With the progression of chemotherapy (CT)and radiotherapy (RT), multidisciplinary measures in surgical treatment of lung cancer has become a hot subject for research. The chairman of ASCO, Dr. Bunn, pointed out that all kinds of cancers should be treated with multidisciplinary methods. Neoadjuvant chemotherapy is standard for care of Ⅲa N 2 NSCLC in Europe and U.S.A., but a large randomized trial was needed to confirm this hypothesis. At the 2003 ASCO meeting, Dr. Le Chevalier reported the result of the randomized international adjuvant lung cancer trial for 1867 resected NSCLC. 2 and 5 yr survival rates, progression free survival (PFS) were superior for the adjuvant CT group. Shanghai Lung Cancer Team studied 211 cases of rescected NSCLC with multi variant cox analyses. The result shows post operation chemotherapy might be beneficial to survival. Besides, in the cases with ≥3 cycles of post operation CT have better survival rates than less cycles. Patients with stage Ⅲa NSCLC and clinical or pathologically confirmed N 2 nodes (pN 2) have a poor prognosis after surgery of RT. Surgical resection after induction CT or CT/RT yields encouraging results in phase Ⅱ trials, but its role is controversial. Dr. Albain reported 429 cases of resectable Ⅲa (pN 2)NSCLC divided into CT/RT/S and CT/RT groups. CT/RT followed by surgery yields superior MST, 3-year survival rates and PFS, but there were more non cancer deaths in CT/RT/S group. The benefit reported could prevent annually-7,000 deaths worldwide.
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Purpose:To study the effectiveness and safety o f first-line chemotherapy with GEM-Cis 3-week regimen in routine care of Chin ese patients with advanced NSCLC. Methods:Gem-Cis 3-week regimen was used as first line chemoth erapy to treat stage Ⅲb/Ⅳ NSCLC patients, measurements of effectiveness includ ed clinical benefit and significant clinical response (SCR), and side events of GEM-Cis in the treatment of stage Ⅲb/IV NSCLC. Results:221 patients with cytological or pathological confirmed stage Ⅲb or IV NSCLC were enrolled, 209 eligible for effectiveness and safety analysis. Median age 58 years (range, 29 to 79 years); males: females, 67.5%∶ 32.5%; stage Ⅳ: ⅢB, 52.5%∶47.8 %; KPS
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Malignant mesothelioma is an aggressive malig na ncy that may be caused by environmental carcinogens(asbestos),viruses(SV40),and genetic predisposition.Diagnosis relies on radiographic studies as well as patho logy and mdecular bidogy tests.Most such patients are not suitable for surgical or radiotherapy treatment,and cytotoxic agents are the only options.Historically ,no single or combinations of agents consistently yielded response rates over 20 %.Recently,pemetrexed,a folate-based inhibitor of thymidylate synthase,has been evaluated in phase Ⅰ,ⅡandⅢ clinical trials with promising results.Moreover, low-dose folic acid and vitamin B 12 supplementation significantly reduced the toxicity observed with the use of pemetrexed.In light of these data,it is l ikely that pemetrexed/cisplatin will soon be recommended for malignant pleural m esothelioma as first-line standard chemotherapy.
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As we know a poor prognosis is seen in locally advanced NSCLC treated with surgery, there have some consistencies and controversies found in a number of surgical studies. Consistency: Incomplete resection of tumor and central T3 tumor have poor 5-yr survival, T3 with N, has a worse long-term survival rate than with N0. Mediastinal lymph node metastasis N2 is known as the most important prognostic factor in stage Ⅲ NSCLC, multiple node stations, location and extra-capsular nodal extension of tumor are unfavorable prognostic indicatiors. Preoperative induction chemotherapy may improve the complete resection and survival of stage M NSCLC, but more multicenter randomized studies are needed to be further study. T4, N, Mb NSCLC are known as having quite a poor prognosis and low resectability. Controversy: Clinical image staging is a noninvasive method to look for intrathoracic lymph node, but it is not as accurate as mediastinoscopy. Post-operative radiotherapy has a lower relapse rate but no benefit to survival. Pre-operative radiotherapy of pancoast tumor has a higher complication rate. 30% of intrathoracic nodes have skip N2 metastasis, thus, careful dissection of all the nodes stations and sample it sent to pathology is necessary. Pneumonectomy is not beneficial to the survival of pN2. Carinaectomy is not suitable for those patients with N1, N2. Malignant pleural effusion is basically a nonsurgical disease.