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Query: UMLS:C0242379 (lung cancer)
 71,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The resectability of NSCLC is determined by its stage. The surgical treatment in stage I and II NSCLC remains a golden standard. Stage IIIA NSCLC constitutes a non-homogenous group, and many patients are potentially non-resectable. The patients in stage IIIA NSCLC also constitute a non-homogenous group. The patients in stage T3N1 usually undergo surgical resection, but many patients with N2 disease are disqualified from surgical treatment due to the negative prognostic factors. The negative prognostic factors comprise: (1) metastases to upper paratracheal (no 2), anterior paratracheal (no 3), and subcarinal (no 7) lymph nodes; (2) metastases to multiple mediastinal lymph nodes; (3) occurrence of the so called 'bulky disease'; (4) capsular lymph node invasion. The occurrence of one of these negative prognostic factors disqualifies the patient with N2 disease from radical surgical treatment. In more advanced cases, i.e. stage IIIB, and stage IV NSCLC, patients are rarely operated. It regards the patients in stage T4 N1, and in M1 disease with a single metastasis (mainly to CNS) accompanied by the stage I, or II, of the primary focus. In these cases N2 disease always constitutes the contraindication to the surgical treatment. Multidisciplinary approach in the treatment of NSCLC is supposed to improve the results of the treatment of NSCLC.
Lung Cancer 2001 Dec
PMID:Surgical treatment of stage III non-small cell lung cancer. 1172 Jul 55

Although new agents and drug combinations have increased the response rate in advanced non-small cell lung cancer (NSCLC), long-term survivors are rare. There is an urgent need to develop new chemotherapeutic approaches for disease. In a previous pilot phase I-II study on 5-aza-2'-deoxycytidine (5-AZA-CdR) in patients with stage IV NSCLC, we observed several interesting responses, including one patient that was still alive (68 months) at the time of publication of our results. In the present report, we want to point out the long-term follow up of this patient, who survived 81 months, and discuss the interesting mechanism of action of 5-AZA-CdR that may have been responsible for this interesting response. 5-AZA-CdR is a potent inhibitor of DNA methylation. Recent progress in this field has shown that aberrant methylation of the promoter region of tumor suppressor genes inhibits their expression. This epigenetic event can contribute to tumorigenesis. Since 5-AZA-CdR can reactivate these genes by blocking DNA methylation, it has the potential to reverse tumorigenesis. This novel mode of action makes it an interesting agent to investigate for the chemotherapy of malignant disease, including lung cancer.
Lung Cancer 2001 Dec
PMID:Potential of 5-aza-2'-deoxycytidine (Decitabine) a potent inhibitor of DNA methylation for therapy of advanced non-small cell lung cancer. 1174 14

Stage IV non-small cell lung cancer (NSCLC) denotes the presence of metastatic disease and is largely incurable using present-day therapies. Chemotherapy remains a therapeutic option in this patient population, and there are many pertinent issues surrounding its use in patients with stage IV NSCLC. Eleven questions were framed by the American College of Chest Physicians Lung Cancer Guidelines Committee, and these were addressed by a systematic search of the available literature. The issues addressed included the identification of prognostic factors in selecting patients for chemotherapy and a critical analysis of the survival benefit provided by chemotherapy. Given the development of several new chemotherapy agents over the past decade, the impact that these agents have made was addressed as well as the definition of a standard of care regarding chemotherapeutic regimens. Given the fact that chemotherapy does not represent a curative option, other issues addressed were the optimal duration of treatment as well as its impact on symptom relief and quality of life, the role of second-line therapy, and the outcomes expectations from both first-line and second-line chemotherapy. The question of what specialty delivered the chemotherapy also was addressed. Once the data were identified, a critical analysis was undertaken attempting to objectively portray the data in support of answers for each of the questions posed. We believe the data support the fact that properly selected patients benefit from chemotherapy with regard to survival and palliation in both first-line and second-line settings. It appears that in trials addressing the duration of first-line therapy, this survival and palliative benefit occurs early, and prolonged therapy is not indicated. Therapy in this setting is cost-effective, and there are several regimens that can be considered to be "standard-of-care" options. Physicians involved in the diagnosis of these patients should be aware of the potential benefits of chemotherapy, allowing them to give recommendations to patients that are based on data derived from clinical trials. In addition, this awareness will allow them to make referrals, when appropriate, to physicians who are trained in the administration of chemotherapy and the management of patients undergoing such therapy.
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PMID:Chemotherapeutic management of stage IV non-small cell lung cancer. 1252 82

A phase II multicentre study of a 3-week schedule of irinotecan (CPT-11) and cisplatin providing the highest recommended dose intensity of both agents in combination, was conducted in patients with advanced non-small cell lung cancer (NSCLC). Seventy-four stage IIIB (not suitable for radiotherapy) or stage IV NSCLC patients were enrolled to receive CPT-11 200 mg/m(2) i.v. and cisplatin 80 mg/m(2) i.v. on day 1 every 3 weeks. Relative dose-intensities for CPT-11 and cisplatin were 92 and 95%, respectively. No complete responses were observed. Twenty-five patients out of 73 obtained a partial response (34.2%). Partial responses were confirmed in 18 patients (24.7%: 95% CI, 15.3-36.1%). Median survival overall was 8.2 months, 9.7 months for patients with baseline performance status (PS) 0 and 1, and 4 months for patients with PS 2. The 1-year survival rate was 31%. Major clinical toxicities were grade 3 and 4 delayed diarrhoea (29% of patients) and febrile neutropenia (14% of patients). In conclusion, the present once-every-3-week schedule of CPT-11 and cisplatin is feasible and active in PS 0-1 advanced NSCLC patients, but results do not seem superior to those reported with other schedules.
Lung Cancer 2003 Feb
PMID:Three-week schedule of irinotecan and cisplatin in advanced non-small cell lung cancer: a multicentre phase II study. 1258 74

We recently reported that regular infusions of adenosine 5'-triphosphate (ATP) inhibited loss of body weight and quality of life in patients with non-small cell lung cancer (NSCLC). In the present paper we investigated whether ATP affects tumor growth and survival in the same group of patients. Fifty-eight NSCLC patients (stage IIIB or IV) were randomly assigned to receive either 10 i.v. 30-h ATP infusions every 2-4 weeks over a 24-week period (n = 28) or no ATP (control patients, n = 30). ATP was given for a median of 6.5 infusions. Differences in time to progression and survival between patients in both groups were tested by means of the log-rank test and Cox regression analysis. Forty-nine patients were evaluable for tumor response. None of the evaluable patients showed a complete or partial response. Median time to progression was 3.9 months [95% confidence interval (CI) = 2.3-5.5] in the ATP group compared to 3.0 months (95% CI = 2.4-3.7) in the control group (p = 0.71). Median survival was 5.6 months (95% CI = 1.1-10.1) for the ATP group and 4.7 months (95% CI = 2.6-6.8) for the control group (p = 0.68). ATP treatment was associated with a significant increase in survival in the subgroup of weight-losing patients with stage IIIB NSCLC: in this subgroup, median survival was 9.3 months (95% CI = 2.1-16.5) for ATP-treated patients versus 3.5 months (95% CI = 2.3-4.7) for control patients (between-group difference: p = 0.009). No significant effect of ATP was observed for weight-losing patients with stage IV NSCLC or for weight-stable NSCLC patients. Although ATP as a single therapy does not lead to tumor regression or increased survival in patients with advanced lung cancer, it may prolong survival in weight-losing patients with stage IIIB lung cancer. The latter finding is intriguing, but requires confirmation in larger clinical trials.
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PMID:Randomized clinical trial of adenosine 5'-triphosphate on tumor growth and survival in advanced lung cancer patients. 1450 86

Activation of coagulation appears to play a role in tumor progression. This report describes the preliminary results of a phase II study using docetaxel plus enoxaparin in 15 patients with stage IV non-small cell lung cancer (NSCLC). Time to progression was the primary endpoint. Several surrogate markers of coagulation and angiogenesis were evaluated. Enoxaparin was administered at a daily dose of 1 mg/kg (subcutaneously). The initial dose of docetaxel was 100 mg/m2, given as a 60 min infusion every 21 days with prophylactic dexamethasone. Eight patients achieved an objective response (53%) and four had stable disease, with a median duration of 3.5 months. The median time to progression was 5 months (range, 2 to >15 months). The median survival was 11 months. The most frequent toxicities were neutropenia and asthenia. No significant bleeding or thrombotic events were observed. Eleven patients had elevated D-dimer plasma levels prior to therapy, and seven of these patients with a response or stable disease had a significant decline of the D-dimer during therapy. There were no consistent changes of the plasma levels of the angiogenic factors, except for transforming growth factor-beta-1 (TGF-beta1). The median baseline level of TGF-beta1 prior to therapy was 34,867 pg/ml. Twelve out of 13 patients who achieved a response or stable disease had a significant reduction of the TGF-beta1 levels during therapy. Enoxaparin in combination with chemotherapy was safe and well tolerated in patients with advanced NSCLC. This preliminary data suggests that enoxaparin may prolong the time to progression, and therefore justify the continuation of this trial.
Lung Cancer 2003 Nov
PMID:Phase II study of docetaxel plus enoxaparin in chemotherapy-naive patients with metastatic non-small cell lung cancer: preliminary results. 1456 92

The purpose of this study was to compare the efficacy and safety profile of docetaxel versus the combination of docetaxel/cisplatin as frontline treatment of patients with advanced or metastatic non-small-cell lung cancer (NSCLC) in a multicenter, randomized, prospective phase III trial. Patients with unresectable stage IIIB or metastatic stage IV NSCLC who had previously undergone no chemotherapy were allocated to receive either docetaxel (100 mg/m2 in a 1-hour intravenous infusion; group A) or the combination of docetaxel (100 mg/m2 day 1) and cisplatin (80 mg/m2 day 2) after adequate hydration (group B). Appropriate premedication was given before docetaxel infusion. All patients in group B received granulocyte colony-stimulating factor (150 microg/m2 subcutaneously) support from days 3 to 9 after treatment. Response and toxicity were assessed by World Health Organization criteria. From March 1999 to November 2001, 302 patients were randomly assigned to receive docetaxel (group A, n = 146) or docetaxel/cisplatin (group B, n = 156). The overall response rate was significantly higher in the combination arm (18% vs. 36%; P < 0.001). However, the 2 groups did not differ in median duration of response, time to progression (TTP), median overall survival (OS), or 1-year survival rate. Drug combination was associated with higher toxicity than single-agent therapy. Both regimens had comparable activity in terms of TTP and OS in chemotherapy-naive patients with advanced NSCLC; however, single-agent therapy had a more favorable toxicity profile.
Clin Lung Cancer 2003 Mar
PMID:Docetaxel versus docetaxel/cisplatin in patients with advanced non-small-cell lung cancer: preliminary analysis of a multicenter, randomized phase III study. 1460 46

In view of favorable reports with the 3-drug combination of PGV (cisplatin/gemcitabine/vinorelbine), this multicenter phase II study evaluated the therapeutic index of PGV in patients with advanced non-small-cell lung cancer (NSCLC). Thirty-two patients with stage IV NSCLC and 1 with stage IIIB were studied. There were 23 men and 10 women, with a median age of 63 years (range, 38-80 years). Twelve patients had a performance status (PS) of 0, and 21 patients had a PS of 1. Treatment consisted of cisplatin 50 mg/m2, gemcitabine 1000 mg/m2, and vinorelbine 25 mg/m2 all given intravenously on days 1 and 8, in 21-day cycles. Fifteen patients (45%; 95% confidence interval (CI), 28%-64%) achieved a partial response. Median response duration was 3 months (range, 1-9 months). The median and 1-year survival rates were 9.4 months and 39% (95% CI, 23%-58%), respectively. The median number of cycles was 4. Only 3 patients (9%) completed treatment without regimen modifications. Median dose intensity (% planned) was cisplatin 24 mg/m2/week (72%), gemcitabine 483 mg/m2/week (72%), and vinorelbine 12 mg/m2/week (72%). Toxicities were predominantly hematologic, with grade 3/4 neutropenia (67%), febrile neutropenia (21%), and thrombocytopenia (67%). There were 3 (9%) treatment-related deaths due to neutropenic complications. This study confirms the substantial antineoplastic activity of PGV. We observed a high rate of severe hematologic toxicity, especially febrile neutropenia, despite a lower delivered dose intensity of PGV. Given these results, PGV appears to offer no therapeutic advantage to current doublet regimens.
Clin Lung Cancer 2002 Jul
PMID:Unfavorable therapeutic index of cisplatin/gemcitabine/vinorelbine in advanced non-small-cell lung cancer. 1465 76

Irinotecan possesses significant single-agent activity in non-small-cell lung cancer (NSCLC) and is active in combination with either cisplatin or carboplatin. Two phase III trials completed in Japan have suggested that the combination of irinotecan/cisplatin yields superior survival rates in stage IV NSCLC patients compared to vindesine/cisplatin. The principal toxicities of the irinotecan/cisplatin regimen are neutropenia and diarrhea. This regimen is currently being tested in Japan against regimens commonly used in the United States, such as cisplatin/gemcitabine, cisplatin/vinorelbine, and carboplatin/paclitaxel. These studies include evaluation of monthly as well as weekly schedules of cisplatin in combination with irinotecan as well as a triplet regimen of irinotecan/carboplatin/paclitaxel. Ongoing trials are evaluating these regimens as well as irinotecan/carboplatin and several nonplatinum-based irinotecan-containing doublets in both the first- and second-line treatment of advanced NSCLC. Several ongoing trials are attempting to integrate irinotecan with thoracic radiation therapy in stage III NSCLC. These trials are using irinotecan-containing regimens as induction and concurrent therapy with thoracic radiation therapy. Irinotecan is also being evaluated in the preoperative setting in early-stage resectable NSCLC. Many of these trials are also incorporating celecoxib, a potent inhibitor of the cyclooxygenase-2 pathway, in combination with irinotecan-containing regimens in both advanced as well as early-stage NSCLC. Future trials should focus on the integration of the new targeted agents in combination with irinotecan-containing regimens in all stages of NSCLC.
Clin Lung Cancer 2002 Nov
PMID:Irinotecan in non-small-cell lung cancer: status of ongoing trials. 1465 36

Chemotherapy in nonsmall-cell lung cancer (NSCLC) is not just a reality but has resulted in important improvements in quality of life and survival for patients with locally advanced and metastatic NSCLC. For patients with stage IV NSCLC, platinum-based 2-drug combinations are superior to single-agent therapy and have a superior therapeutic index than 3-drug combinations. Concurrent chemoradiation has become the standard of care for patients with locally advanced NSCLC. The addition of consolidation chemotherapy following definitive chemoradiation appears to improve median survival. The era of molecularly targeted therapies for NSCLC is here. Early results with some of the targeted agents studied for the treatment of NSCLC have generated a great deal of excitement. In this article, we review the results of recent clinical trials in locally advanced and metastatic NSCLC.
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PMID:Results of clinical trials for locally advanced and metastatic nonsmall-cell lung cancer. 1471 Mar 86


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