Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0684249 (lung carcinoma)
 23,830 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Preoperative chemotherapy in patients with stage III non-small-cell lung cancer (NSCLC) remains controversial. Phase II trials utilizing preoperative chemotherapy in selected patients have achieved complete resection rates of 50%-70% with 3-5 year failure-free survival rates of 15%-33%. Between October 1992 and November 1994, 57 adults (50 of whom were evaluable) with surgically staged IIIA NSCLC and pathologically documented ipsilateral mediastinal nodal involvement (N2) were enrolled in a Cancer and Leukemia Group B randomized trial. Preoperative therapy was thought to be critical to facilitating surgical resectability. For patients randomized to the radiotherapy/surgery/radiotherapy (RSR) arm (n = 24), treatment consisted of preoperative radiation therapy (RT) at 40 Gy, surgery, and then additional RT at 14-20 Gy. For patients randomized to the chemotherapy/surgery/chemotherapy/radiotherapy (CSCR) arm (n = 26), treatment consisted of 2 cycles of cisplatin/etoposide with filgrastim support (PE) followed by surgery, 2 more cycles of PE, then RT 54-60 Gy. The total dose of RT on either arm was 54 Gy if completely resected or 60 Gy if incompletely resected or unresected. Clinical characteristics were well balanced between the two arms. Thoracotomy was performed in 42 patients (84%), 28 (67%) of whom had complete resection. The median failure-free and overall survival rates were 12 months (95% confidence interval [CI], 9-23 months) and 23 months (95% CI, 19 months-infinity) for the RSR arm and 11 months (95% CI, 5-20 months) and 18 months (95% CI, 12-32 months) for the CSCR arm. The rates of overall and complete surgical resection, downstaging of nodal involvement, and failure-free (P = 0.92) and overall survival (P = 0.41) did not differ between the two treatment arms. Moreover, in this trial, the chemotherapy regimen was sufficiently toxic to have had a lower completion rate of prescribed therapy in the CSCR arm than in the RSR arm.
Clin Lung Cancer 2002 Sep
PMID:Radiotherapy versus chemotherapy plus radiotherapy in surgically treated IIIA N2 non-small-cell lung cancer. 1465 65

Chemotherapy for extensive-stage small-cell lung cancer (E-SCLC) produces high response rates and improved survival but few cures. We tested three new regimens for E-SCLC that might merit further investigation in a subsequent phase III trial. Cancer and Leukemia Group B 9430 was a randomized phase II study evaluating 4 treatment arms in 57 evaluable, previously untreated E-SCLC patients. Each arm consisted of the following: Arm 1: cisplatin plus topotecan; Arm 2: cisplatin plus paclitaxel; Arm 3: paclitaxel 230 mg/m2 plus topotecan; and Arm 4: paclitaxel 175 mg/m2 plus topotecan. Because of an accrual time difference, Arm 2 will not be discussed in this manuscript. Arm 1 (12 patients) produced 1 complete response (CR, 8%) and an overall response rate (ORR) of 42%. Toxicity was excessive, with 3 deaths (25%). Arm 3 (13 patients) produced no CRs, 7 partial responses (PRs, 54%), median survival of 13.8 months, and failure-free survival (FFS) of 7.41 months, with 3 toxic deaths (25%). Among 32 evaluable patients on Arm 4, there were 2 CRs (6%) and 20 PRs (63%) for an ORR of 69%, median survival of 9.9 months, FFS of 5.21 months, and 1-year survival of 40%. There was 1 possible treatment-related death (3%). Topotecan plus cisplatin, in the doses and schedule employed, produced excessive toxicity and modest efficacy in E-SCLC patients. Paclitaxel (230 mg/m2 on day 1) plus topotecan (1 mg/m2 on days 1-5) produced excessive toxicity that was ameliorated with an attenuated paclitaxel dose (175 mg/m2). With the latter regimen (Arm 4) in patients with a performance status of 0/1, CR rates, FFS, overall survival, and 1-year survival were similar to standard etoposide plus cisplatin chemotherapy. Further exploration of topoisomerase inhibitors and taxanes in SCLC patients is warranted.
Clin Lung Cancer 2002 Feb
PMID:Novel doublets in extensive-stage small-cell lung cancer: a randomized phase II study of topotecan plus cisplatin or paclitaxel (CALGB 9430). 1466 44

The median survival for patients with locally advanced non-small-cell lung cancer (NSCLC) remains 18 months, at best, in cooperative group efforts. Integrating new agents into the standard combined modality treatment paradigm is a daunting challenge. Gemcitabine has activity in advanced NSCLC and is a potent radiosensitizer, but preclinical trials did not delineate an optimal dose or schedule, and early attempts to graft full-dose gemcitabine (1000 mg/m2/week) onto standard radical thoracic radiation therapy (RT) were marked by significant grade 4 and 5 toxicity. More recent trials, however, have shown that attenuated doses of 150-300 mg/m2/week during radiation (XRT) are safer and potentially efficacious. Higher doses produce dose-limiting esophageal and pulmonary toxicities. Using a twice-weekly schedule, the maximum tolerated dose is 35 mg/m2. The use of 3 dimensional conformal RT may enable significant dose escalations while substantially reducing esophageal exposure and minimizing toxicity. The cooperative oncology groups are just beginning to evaluate gemcitabine in this setting. Cancer and Leukemia Group B, in a randomized phase II study, assessed combination gemcitabine and cisplatin in both the induction and radiosensitizing setting. During the induction phase, gemcitabine was given 1250 mg/m2 on days 1 and 8 every 3 weeks for 2 cycles in combination with cisplatin 80 mg/m2 every 3 weeks, and then reduced to 600 mg/m2 days 1 and 8 every 3 weeks during XRT. The overall response rate was 63% with median survival of 18.3 months and 1-year and 3-year survival rates of 68% and 28%, respectively. Radiation Therapy Oncology Group is currently spearheading a phase I study of concurrent radiation and weekly gemcitabine in combination with either weekly carboplatin or paclitaxel. Ongoing efforts will also evaluate the role of gemcitabine either alone or in combination with docetaxel in the consolidation setting after definitive chemoradiation has been completed. Whether gemcitabine in combination with radiation, with or without other agents, will ultimately prove superior to standard chemoradiation regimens remains to be determined.
Clin Lung Cancer 2003 Jan
PMID:The emerging role of gemcitabine in combination with radiation in locally advanced, unresectable non-small-cell lung cancer. 1472 Mar 36

Surgical resection of early-stage non-small-cell lung cancer (NSCLC) remains the standard of care in patients fit for surgery. Careful preoperative staging is imperative, as is pathologic documentation of the mediastinal nodal contents. Adjuvant postoperative thoracic radiation therapy (RT) clearly has an impact in reducing locoregional recurrence but has no clear impact on survival. The Postoperative RT (PORT) metaanalysis raised concerns about PORT, particularly in stage I/II NSCLC, suggesting it may negatively impact survival. This was not a concern in stage III NSCLC, in which the risk of locoregional recurrence is higher. However, distant recurrence remains the dominant pattern in resected NSCLC, suggesting that the majority of patients with early-stage resected NSCLC harbor occult micrometastatic disease. Historically, the role of adjuvant chemotherapy has been controversial, and its routine use was not supported by the published data, which consisted of a small number of underpowered trials using inadequately delivered, antiquated chemotherapy. More recently, larger trials have been reported with conflicting results. Like adjuvant PORT, chemotherapy combined with RT has not improved survival over PORT alone. The use of adjuvant cisplatin-based therapy did not show a survival advantage in the Adjuvant Lung Project Italy study but did in the International Adjuvant Lung Trial, creating controversy in the routine implementation of adjuvant therapy in all patients. Recently completed randomized trials by the Cancer and Leukemia Group B and the National Cancer Institute of Canada provide convincing evidence of a substantial benefit from adjuvant therapy in well-staged and completely resected stage I/II NSCLC. Currently, the totality of the data supports a discussion with patients with resected NSCLC regarding the potential benefits of adjuvant therapy.
Clin Lung Cancer 2004 Nov
PMID:Adjuvant therapy of resected non-small-cell lung cancer. 1555 17

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality in the United States. Patients with early stage NSCLC have a reasonable chance of cure with surgery, but unfortunately, fewer than half of all newly diagnosed NSCLC patients are surgical candidates. In addition, less than half of all patients treated with surgical resection alone are ultimately cured of their disease. As a result, several studies have emerged over the past decade examining the role of adjuvant chemotherapy as a means of improving outcomes in early-stage NSCLC. This article highlights the background and rationale, as well as the major findings, of each of these studies, namely, the British Medical Journal meta-analysis, the Adjuvant Lung Project Italy study, the Japanese Lung Cancer Research Group study, the International Adjuvant Lung Cancer Trial, the Cancer and Leukemia Group B 9633 study, and the JBR.10 study. From these collective studies, a new standard of care has emerged in the treatment of early-stage resected NSCLC: the use of adjuvant platinum-based chemotherapy.
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PMID:The role of adjuvant chemotherapy for non-small cell lung cancer. 1605 31

Lung cancer is the leading cause of cancer-related mortality in the developed world. Non-small cell lung cancer (NSCLC) represents 85% of cases of lung cancer, and patients have a poor 5-year survival rate. Approximately one third of NSCLC patients present with early-stage disease that is amenable to potentially curative resection and multimodality therapy. Several randomized trials now have confirmed the survival benefit with adjuvant platinum-based chemotherapy, as seen in the 1995 meta-analysis from the NSCLC Collaborative Group. The International Adjuvant Lung Cancer Collaborative Group Trial demonstrated a 4.5% improvement in survival for patients with stage I to III NSCLC. Studies from Japan have reported an improvement of 15.4% in the 5-year survival rate among patients with T1N0 disease after they had received adjuvant therapy with a combination of platinum and uracil-tegafur, and an improvement in the 5-year survival of 11% rate favoring chemotherapy with uracil-tegafur in a subgroup analysis of patients with T2N0 disease. Two recently published meta-analyses have estimated a relative risk reduction in mortality of 11 to 13% at 5 years. Significant improvement in the long-term survival rate has been demonstrated for patients with stage IB and II disease by the Cancer and Leukemia Group B 9633 trial (4-year survival rate, 12%) and the The National Cancer Institute of Canada Clinical Trials Group BR.10 trial (5-year survival rate, 15%; risk reduction for recurrence, 40%). Thus, there is compelling evidence to now recommend adjuvant platinum-based combination chemotherapy for patients after resection of early-stage NSCLC.
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PMID:Adjuvant Chemotherapy for Early-Stage Non-small Cell Lung Cancer. 1623 70

Elderly patients and those with performance status (PS) of 2 with non-small-cell lung cancer (NSCLC) have been habitually underrepresented in clinical trials. Therapeutic neglect and legitimate concerns about toxicity are responsible. Yet randomized phase III data in the elderly have demonstrated a survival benefit for single-agent chemotherapy compared with best supportive care, and retrospective analyses of fit elderly patients enrolled on platinum agent-based trials have shown similar survival rates, albeit more toxicity, compared with younger counterparts. To date, however, there are no phase III trials specific to the elderly population demonstrating a survival benefit for platinum agent-based combinations compared with the constituent nonplatinum single agent; such efforts are ongoing. Performance status is a critical prognostic factor in advanced-stage NSCLC. Retrospective analyses of multiple trials conducted before 1995 suggested that patients with advanced-stage NSCLC and compromised PS experienced substantial toxicity and virtually no benefit from systemic chemotherapy, leading most cooperative groups to suspend research in this cohort. But this trend has changed. A subset analysis of patients with a PS of 2 enrolled on a recent Cancer and Leukemia Group B trial showed a significant survival benefit for carboplatin in combination with paclitaxel compared with paclitaxel alone, and recent randomized phase II efforts evaluating platinum agent-based combinations have yielded median survival times of > 6 months with acceptable toxicity rates. Although the Selective Targeting for Efficacy in Lung Cancer, Lower Adverse Reaction trials testing polyglutamated paclitaxel failed to show a survival advantage compared with standard agents, interest in testing new, less toxic agents continues. Future efforts will need to differentiate the reasons for compromised PS, be it tumor burden, comorbidity, or both.
Clin Lung Cancer 2006 May
PMID:Neglected and underrepresented subpopulations: elderly and performance status 2 patients with advanced-stage non-small-cell lung cancer. 1676 53

Adjuvant chemotherapy after resection of stage II-IIIA non-small-cell lung cancer is now the standard of care based on the results of 3 phase III studies using cisplatin-based regimens, IALT (International Adjuvant Lung Trial), The National Cancer Institute of Canada JBR.10, and ANITA (Adjuvant Navelbine International Trialist Association). The role of adjuvant chemotherapy for stage IB disease remains controversial, even more so now that the updated results from CALGB (Cancer and Leukemia Group B) trial 9633 are statistically negative. CALGB 9633 was the only randomized adjuvant trial to use a carboplatin backbone and focused exclusively on patients with stage IB disease. Initial results, reported in 2004, showed a significant survival advantage with the addition of chemotherapy, but the 2006 updated results are no longer statistically significant. The next large intergroup adjuvant trial in non-small-cell lung cancer will look at bevacizumab in combination with chemotherapy. Because of the recent update, this trial will now limit patients with stage IB disease to those with larger tumors (>or= 4 cm) and will likely include only cisplatin-based regimens.
Clin Lung Cancer 2006 Jul
PMID:Current status of adjuvant chemotherapy for stage IB non-small-cell lung cancer: implications for the New Intergroup Trial. 1687 41

Ageratum conyzoides has been used in folklore for the treatment of a wide range of diseases. In the present investigation, the in vitro activity of ethanol, petroleum ether, ethylacetate, butanol, and water extracts of A. conyzoides were screened in some cancer cell lines using the sulphorhodamine B (SRB) assay. These cell lines include: Human non-small cell lung carcinoma (A-549), human colon adenocarcinoma (HT-29), human gastric carcinoma (SGC-7901), human golima (U-251), human breast carcinoma (MDA-MB-231), human prostate carcinoma (DU-145), human hepatic carcinoma (BEL-7402), and mouse leukemia (P-388) cancer cell lines. Furthermore, kaempferol was isolated from the ethylacetate extract and the structure was elucidated by nuclear magnetic resonance (NMR) and mass spectroscopy. The effect of DPPH antiradical activity on the extracts and kaempferol was also determined. The results showed that ethylacetate extract exhibited the highest cytotoxic activity on A-549 and P-388 cancer cells with IC(50) values of 0.68 and 0.0003 mug/ml, respectively. Kaempferol isolated from the ethylacetate extract of A. conyzoides rapidly scavenged DPPH at a concentration of 130.07 +/- 17.36 g/kg. The result therefore showed that A. conyzoides possessed anticancer and antiradical properties.
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PMID:Anticancer and antiradical scavenging activity of Ageratum conyzoides L. (Asteraceae). 2054 38

To the Editor: We would like to retract our article, "A Genomic Strategy to Refine Prognosis in Early-Stage Non-Small-Cell Lung Cancer,"(1) which was published in the Journal on August 10, 2006. Using a sample set from a study by the American College of Surgeons Oncology Group (ACOSOG) and a collection of samples from a study by the Cancer and Leukemia Group B (CALGB), we have tried and failed to reproduce results supporting the validation of the lung metagene model described in the article. We deeply regret the effect of this action on the work of other investigators.
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PMID:Retraction: A genomic strategy to refine prognosis in early-stage non-small-cell lung cancer. N Engl J Med 2006;355:570-80. 1689 77


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