Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242379 (lung cancer)
 71,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

During the last decade, the Eastern Cooperative Oncology Group (ECOG) has studied a series of combination chemotherapy regimens in metastatic (stage IV) non-small-cell lung cancer (NSCLC). In January 1984, the ECOG activated a randomized study, EST 1583, which concluded the evaluation of combination regimens in phase III trials and initiated the evaluation of single agents exclusively in previously untreated patients. The treatment regimens in EST 1583 consisted of: (1) mitomycin, vinblastine, and cisplatin (MVP); (2) vinblastine and cisplatin (VP); (3) MVP alternating with the regimen cyclophosphamide, doxorubicin, methotrexate, and procarbazine (CAMP); (4) carboplatin followed by the MVP regimen at the time of progression; and (5) iproplatin followed by MVP at the time of progression. From January 1984 to July 1985, 743 patients were entered on this trial and 699 fulfilled the eligibility requirements. The following objective response rates (complete plus partial remissions) were observed: first-line MVP, 20%; VP, 13%; MVP/CAMP, 13%; carboplatin, 9%; iproplatin, 6%; and second-line MVP, 6%. First-line MVP produced a significantly higher response rate than the other treatments (P = .03) adjusted for prognostic variables. Using analyses that were adjusted for prognostic covariates, survival for patients treated on a given regimen was compared with survival for all remaining patients. These analyses showed that treatment with carboplatin was associated with longer survival (median survival time, 31.7 weeks; P = .008) while initial treatment with MVP was associated with a trend for shorter survival (median survival time, 22.7 weeks; P = .09). It should be noted that none of these regimens appear to have produced a clinically meaningful prolongation of survival. Similar analyses evaluating time to progression disclosed that carboplatin-treated patients had a significantly longer time to progression (median time to progression, 29 weeks) than all remaining patients (P = .01). Life-threatening and lethal toxicities (toxicity grades 4 and 5) were greater on the combination regimens than on the single agents (P less than .0001). Based on these results, current group-wide ECOG trials in stage IV NSCLC consist of randomized phase II trials evaluating single agents.
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PMID:Combination chemotherapy versus single agents followed by combination chemotherapy in stage IV non-small-cell lung cancer: a study of the Eastern Cooperative Oncology Group. 255 79

Non-small-cell lung cancer (NSCLC) is the most common cause of cancer-related death in the United States. Only about 30% of patients present with surgically resectable (and thus curable) disease. Because existing chemotherapeutic regimens are never curative in advanced NSCLC and because the median survival time is only modestly increased, the Eastern Cooperative Oncology Group (ECOG) has concentrated on a broad phase II testing program designed to identify new agents with activity against the disease. Of the more than one dozen drugs that have been thus evaluated during the past 10 years, only paclitaxel (Taxol) has been shown to result in an objective response rate of more than 20%. To determine if the paclitaxel-containing regimen can increase survival, ECOG has, therefore, embarked on a phase III trial (E5592) in which patients with stage IV NSCLC are randomly assigned to receive either cisplatin plus etoposide (the current standard chemotherapy) or cisplatin plus paclitaxel. The trial design should also help to determine the appropriate dose of paclitaxel in this clinical setting.
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PMID:Phase III trial (E5592) comparing cisplatin plus etoposide with cisplatin plus paclitaxel at two dose levels for treatment of advanced non-small-cell lung cancer. Eastern Cooperative Oncology Group. 757 8

Recent progress in chemotherapy for advanced nonsmall cell lung cancer (NSCLC) and small cell lung cancer (SCLC) maybe summarized as follows. 1) In seven randomized trials of combination chemotherapy compared with best supportive care in stage IV NSCLC, meta-analysis of indicated that combination chemotherapy modestly improves survival of patients with advanced NSCLC. 2) Cisplatin-based combination chemotherapy followed by chest irradiation improves outcomes of patients with stage III unresectable NSCLC as compared with radiation therapy alone. 3) Meta-analysis has shown that survival is prolonged when radiotherapy is used in combination with chemotherapy in the treatment of limited-stage SCLC. 4) Randomized trials evaluating alternating chemotherapy could not demonstrate the survival benefit in the treatment of extensive-stage (ES) SCLC. 5) The approach to increasing dose intensity has been attempted in the treatment of ES-SCLC. The most common approach is weekly chemotherapy. Results of pilot studies have suggest that this approach prolong survival of patients with ES-SCLC. 6) Recently, several new drugs active against NSCLC and SCLC, including CPT-11, taxol, axotere, vinorelbine and gemcitabine, have been developed. In conclusion, despite these advances of treatment, the cure rate remains quite low in lung cancer. Further investigations are needed to improve the treatment results for patients with this disease.
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PMID:[Recent progress in chemotherapy for advanced lung cancer]. 788 37

Whereas non-small cell lung cancer (NSCLC) comprises 80% of all lung cancer cases, effective prolongation of survival in NSCLC patients using currently available combination chemotherapy has been problematic. Use of dose-intensive chemotherapy along with hematopoietic growth factor support is an attractive, albeit experimental, alternative. We have conducted a phase I study to determine the maximum tolerated dose of etoposide in the ifosfamide/carboplatin/etoposide (ICE) regimen when used with granulocyte-macrophage colony-stimulating factor (GM-CSF) support. Twenty-three patients with solid tumors refractory to standard treatment who had not received previous platinum-containing chemotherapy or for whom there was no generally accepted curative therapy were treated. We present results obtained in 11 patients with previously untreated stage IV NSCLC. The use of ICE plus GM-CSF demonstrated promising activity in this group of patients; the overall response rate was 64%, and median survival was 10.0 months. The maximum tolerated dose of this regimen is 900 mg/m2 etoposide in combination with 5 g/m2 ifosfamide, 400 mg/m2 carboplatin, and 5 micrograms/kg/d GM-CSF.
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PMID:Dose-intensive ifosfamide/carboplatin/etoposide plus granulocyte-macrophage colony-stimulating factor for non-small cell lung cancer. 820 78

Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) given as a 1-hour infusion potentially offers its recipients reduced toxicity, demonstrated efficacy, and greater ease of administration. To confirm this hypothesis, we undertook a phase I/II study of 1-hour, single-agent paclitaxel in 164 patients' refractory malignancies; 59 patients with recurrent or stage IV non-small cell lung cancer (NSCLC) participated in the study. Our objective was to compare two paclitaxel doses (135 and 200 mg/m2) and two 1-hour infusion schedules (1 hour in 1 day, or 1 hour each day for 3 days, divided dose). Results from this study show that paclitaxel given over 1 hour possesses marked antitumor activity. In patients with NSCLC, the overall response rate was 25%, with a higher response rate among higher-dose recipients (31% v 12%). These promising results with single-agent paclitaxel prompted phase II trials of combination therapy incorporating the 1-hour paclitaxel infusion. Twenty-three patients with locally advanced, unresectable stage IIIA or IIIB NSCLC have been treated with 1-hour paclitaxel and cisplatin/etoposide plus radiation therapy. Three patients have had complete responses (CRs) and another five have had "near CRs," defined as only nonspecific abnormalities in previously irradiated areas on computed tomography. Five patients had partial responses. Although the median follow-up is only 9 months, it is encouraging that disease has recurred in only one of the eight patients with CR or near CR and that toxicity has been manageable. Another phase II trial is evaluating 1-hour paclitaxel, carboplatin, and extended-schedule etoposide in patients with limited or extensive small cell lung cancer. Of the 22 patients now evaluable for response (median follow-up, 8 months), 10 (six with limited and four with extensive small cell lung cancer) have achieved CRs and 11 have achieved partial remissions. The regimen is well tolerated. The final results of these and other phase II trials should help clarify optimal paclitaxel schedules and regimens for large-scale randomized trials in patients with lung cancer.
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PMID:Paclitaxel in lung cancer: 1-hour infusions given alone or in combination chemotherapy. 864 70

Because lung cancer is a major health care problem in Canada, it would be useful to identify the direct health care costs of diagnosing and treating this disease and to create an analytic framework within which diagnostic and therapeutic options can be assessed. This paper describes a method of modelling the costs of care for lung cancer. The perspective of the costing model is that of the government as payer in a universal health care system. Clinical algorithms were developed to describe the management of non-small cell (NSCLC) and small cell (SCLC) lung cancer. Patients were allocated to the treatment algorithms in the model, based on a knowledge of the stage distribution of cases within provincial cancer registries and an estimate of the use of therapeutic modalities, according to lung cancer experts. A microsimulation model (POHEM) developed at Statistics Canada was used to integrate data on risk factors, disease onset and progression, health care resource utilization and direct medical care costs. The model incorporates survival data on patients, according to cell type and stage, based on published studies. Relapse and terminal care costs were assigned during the year of death, in order to determine the cost of continuing care and the cumulative cost of lung cancer management over time. Patients surviving five years were assumed to be cured. The model estimates that the total five year cost to provide care to the 15,624 cases of lung cancer diagnosed in Canada in 1988 was in excess of $328 million. Over 82% of this total was spent in the first year for diagnostic tests, therapy (surgery, chemotherapy, radiation therapy, or combinations of these), hospitalization and follow-up costs. The average five year cost per case was $21,000, and ranged from a high of $29,860 for limited disease SCLC, to a low of $16,500 for Stage IV NSCLC. The actual cost of providing care, including the management of complications, is unknown and our estimates should be regarded as an idealized estimate of the cost of lung cancer management. However, the POHEM model has a level of sophistication which, we believe, reasonably reflects the cost per case and total costs of treating lung cancer by stage and therapeutic modality in Canada.
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PMID:Estimating the cost of lung cancer diagnosis and treatment in Canada: the POHEM model. 877 Apr 57

Statistics Canada (Ottawa, Canada) is developing a population health model (POHEM) that simulates the health and common illnesses of Canadians. The POHEM incorporates a model of lung cancer management based on Canadian practice, which has been used to estimate the total direct care costs of treating all lung cancer cases diagnosed in Canada in 1988. One of the potential uses of the POHEM is to evaluate the cost and cost effectiveness of new therapeutic interventions as they are introduced into practice. Gemcitabine, a new nucleoside analog with a broad spectrum of antitumor activity, has been evaluated in the model and estimates have been made of its cost effectiveness in the management of lung cancer over a range of drug costs per treatment cycle ($Cdn 800 to $Cdn 1,800). The survival of stage IV non-small cell lung cancer (NSCLC) patients treated on an international trial of gemcitabine (E018) was used to estimate the potential survival gain relative to the survival of stage IV NSCLC patients managed with best supportive care on a randomized trial conducted by the National Cancer Institute of Canada. Sensitivity analyses were performed assuming that the survival benefit was 25% and 50% less than that reported in the E018 trial. Based on the apparent survival advantage of the E018 trial, the cost per life-year gained ranged from $Cdn 1,609 to $Cdn 9,529 depending on the cost per treatment cycle. At the greatest cost per cycle ($Cdn 1,800) and with survival reduced by 50% as compared with the E018 result, the cost per life-year gained was estimated to be $Cdn 16,230. From these estimates of direct care costs in the Canadian health care system, gemcitabine appears to be a cost-effective intervention for advanced NSCLC.
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PMID:An estimate of the cost effectiveness of gemcitabine in stage IV non-small cell lung cancer. 889 88

Statistics Canada (Ottawa, Ontario, Canada) is in the process of developing the Population Health Model to simulate the health and common illnesses of Canadians. The Population Health Model incorporates a lung cancer module that is based on contemporary Canadian practice. This microsimulation model can be used to estimate the total direct care costs of treating all lung cancer cases diagnosed in Canada and to evaluate the cost and cost-effectiveness of new therapeutic interventions as they are introduced into practice. Gemcitabine, a new nucleoside analogue with a broad spectrum of antitumor activity, is about to be introduced on the Canadian market. The Population Health Model has been used to estimate the cost-effectiveness of gemcitabine in the management of lung cancer over a range of drug doses per treatment cycle starting at 1,000 mg/m2 weekly x 3, as well as potential survival benefits. The survival of stage IV non-small cell lung cancer (NSCLC) patients treated on an international trial of gemcitabine (EO-18) was used to estimate the potential survival gain relative to the survival of stage IV NSCLC patients managed with best supportive care on a randomized trial conducted by the National Cancer Institute of Canada (BR 5). Sensitivity analyses were performed assuming that the survival gain was 25% or 50% less than that reported in the EO-18 trial. The perspective of the economic analysis is that of the government as payer in a universal health care system, and all costs are expressed in 1993 Canadian dollars. Based on the apparent survival advantage of the EO-18 trial in comparison to best supportive care, the cost per life-year gained ranged from $632 to $9,285, depending on the dose per treatment cycle. At the highest dose per cycle (2,000 mg/m2) and with survival reduced by 50% as compared with the EO-18 result, the cost per life-year gained was estimated to be $17,390. From these estimates of direct care costs in the Canadian health care system, gemcitabine appears to be a cost-effective intervention for advanced NSCLC.
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PMID:Cost-effectiveness of gemcitabine in stage IV non-small cell lung cancer: an estimate using the Population Health Model lung cancer module. 919 82

There are few reports on the p53 status of small cell lung cancer (SCLC) and advanced non-SCLC (NSCLC) because surgically resected specimens are generally not available. Therefore, we evaluated p53 immunostaining in 175 transbronchial biopsy (TBB) specimens obtained from patients with all stages of lung cancer and retrospectively evaluated the relationship between p53 status and clinical parameters. All of the specimens were obtained prior to therapy. Formalin-fixed, paraffin-embedded TBB specimens were immunostained using an anti-p53 antibody (DO-1). p53 protein was detected in 55% (61 of 111) of NSCLCs and 58% (37 of 64) of SCLCs. The rate of positivity increased significantly with increasing stage (stages I and II, 45%; stage III, 54%; stage IV, 66%), but not with other clinical parameters. Ninety-five patients were evaluated for their response to chemotherapy. Positive staining for p53 correlated significantly with unresponsiveness to chemotherapy in NSCLC (response rate of 13 versus 60%; P = 0.006), but not in SCLC (80 versus 57%; P = 0.22). p53 positivity was a statistically significant negative prognostic factor for stage III and stage IV NSCLC (P = 0.02), but not for stage I and stage II NSCLC (P = 0.79). There was no survival difference relative to p53 status in SCLC (P = 0.35). These results indicate that p53 overexpression in TBB specimens predicts poor prognosis and chemoresistance in advanced stage NSCLC.
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PMID:The utility of p53 immunostaining of transbronchial biopsy specimens of lung cancer: p53 overexpression predicts poor prognosis and chemoresistance in advanced non-small cell lung cancer. 981 99

Optimal treatment in elderly (> 70 years) with stage IV non-small cell lung cancer (NSCLC) is not known. In order to define it, concurrent short-term chemotherapy (CHT) and palliative radiotherapy (RT) was evaluated in this patient population. Between January 1988 and June 1993, a total of 50 patients entered into a study that used two cycles of carboplatin (CBDCA), 300 mg/m2, days 1 and 29 and oral etoposide, 50 mg/m2, days 1-21 and 29-42. RT was administered with dose of 14 Gy in two fractions given with 1 week split, days 1 and 8. Of 47 patients evaluable for the response, there were three (6%) complete response (CR), and ten (21%) partial response (PR), making the overall response rate of 13 (28%). Response duration ranged 2-8 months (median, 5 months; mean, 5 months). Median survival time (MST) for all 50 patients was 7 months and 1-3 year survival rates were 31, 4.1, and 2%, respectively. There were only nine (19%) patients experiencing hematological grade 3 toxicity, all other CHT-induced toxicity being grade 1 or 2. Of RT-induced high-grade toxicity, grade 3 esophageal was observed in nine (19%) patients while only four (9%) patients experienced grade 3 bronchopulmonary toxicity. No grade 4 or 5 toxicity occurred during this study. Short-course CHT and palliative RT in elderly patients with stage IV NSCLC was well tolerated with mild to moderate toxicity. Together with results obtained this way, they warrant further studies evaluating the effectiveness of this approach and possible CHT- and/or RT-dose escalation in elderly patients with stage IV NSCLC.
Lung Cancer 1999 Apr
PMID:Short-term chemotherapy and palliative radiotherapy for elderly patients with stage IV non-small cell lung cancer: a phase II study. 1040 88


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