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)

The aims of chemoprevention in lung cancer are to prevent the appearance of disease (primary prevention) and to stop or reverse the progression of premalignant lesions (secondary prevention). Until recently, there was little hope that these goals could be attained. However, the results achieved with tamoxifen in the prevention of breast cancer, and the emergence of new therapies specifically targeted to molecules involved in the pathogenesis of lung cancer have set the stage for investigation of these agents for chemoprevention of lung cancer. Two of these new molecular targeted agents are gefitinib, an inhibitor of epidermal growth factor receptor-tyrosine kinase activity, and tipifarnib (R115777, Zarnestra ), an inhibitor of the farnesyltransferase enzyme, which is required for the proper localization and function of the ras oncogene. Tumor responses and disease stabilization have been achieved with both agents in clinical trials. In the Iressa Dose Evaluation in Advanced Lung Cancer (IDEAL)-1 and IDEAL-2 phase II trials, gefitinib was demonstrated to be effective for disease control in patients with advanced non-small-cell lung cancer. The SPORE (Specialized Program of Research Excellence) Trials of Lung Cancer Prevention (STOP) are 2 parallel studies that will investigate the potential effectiveness of gefitinib and tipifarnib in preventing the appearance and progression of premalignant lesions in former or current smokers with a history of smoking-related cancer. These trials should provide information not only about the potential role of gefitinib and tipifarnib in lung cancer chemoprevention, but also about the molecular changes that underlie tumorigenesis and that may serve as markers of disease progression. The STOP trial objectives are to evaluate the effect of gefitinib and tipifarnib on histologic and biologic parameters in patients with evidence of sputum atypia, to evaluate various parameters as potential predictors of the effectiveness of these agents, and to evaluate the tolerability of these agents over a 6-month course of treatment. Histologic response, defined as prevention of appearance or progression of premalignant lesions, is the primary endpoint of these trials. New targeted molecular therapies such as gefitinib and tipifarnib may offer the opportunity to make chemoprevention a viable treatment modality in lung cancer as well as in other human solid tumors.
Clin Lung Cancer 2003 Sep
PMID:Primary and secondary prevention of non-small-cell lung cancer: the SPORE Trials of Lung Cancer Prevention. 1464 93

The epidermal growth factor receptor (EGFR) signaling pathway plays an important role in a number of processes that are key to tumor progression, including cell proliferation, angiogenesis, metastatic spread, and inhibition of apoptosis. EGFR is expressed or overexpressed in non-small-cell lung cancer (NSCLC), and EGFR-mediated growth has been associated with advanced disease and poor prognosis in NSCLC patients. ZD1839 (Iressa) is an orally active, selective EGFR-tyrosine kinase inhibitor that blocks EGFR signal transduction. In preclinical studies using NSCLC cell lines, ZD1839 has been shown to inhibit tumor cell growth. In addition, ZD1839, as monotherapy and in combination with commonly used cytotoxic agents, has produced growth delay in NSCLC human xenografts. Preliminary results from phase I trials in patients with advanced disease have shown that ZD1839 has excellent bioavailability, an acceptable tolerability profile, and promising clinical activity in patients with a variety of tumor types, particularly in NSCLC. ZD1839 is currently in phase III clinical development for the treatment of advanced NSCLC.
Clin Lung Cancer 2001 Aug
PMID:ZD1839 (Iressa) in non-small-cell lung cancer. 1465 86

Gefitinib ("Iressa", ZD1839), an epidermal growth factor receptor tyrosine kinase inhibitor, has recently been approved in several countries for use in advanced or metastatic non-small-cell lung cancer (NSCLC). In contrast to chemotherapies, which are generally used at or near their maximum-tolerated dose (MTD), gefitinib is used at an optimal biological dose (250 mg day(-1)), which is substantially below its MTD, minimising the risk of adverse events without compromising efficacy. Tolerability data from the compassionate use of gefitinib in the "Iressa" Expanded Access Programme support the favourable safety profile of the agent reported in Phase I and II trials. In both settings, the majority of adverse drug reactions were mild/moderate and consisted mainly of grade 1/2 diarrhoea and skin rash. Although skin rash has been suggested to predict response to gefitinib, available data do not support this hypothesis. Overall, these tolerability data demonstrate that gefitinib has a relatively benign side-effect profile and is a well-tolerated treatment option for patients with previously treated NCSLC, who currently have few alternatives.
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PMID:Tolerability of gefitinib in patients receiving treatment in everyday clinical practice. 1466 Oct 47

Some subgroups of patients with advanced/metastatic non-small-cell lung cancer (NSCLC) are frequently considered ineligible for the aggressive, platinum-based combination chemotherapy that is the recommended treatment. Elderly patients may have a poorer tolerance of chemotherapy due to impaired organ function and frequent comorbidities; patients with poor performance status (PS; > or =2 due to NSCLC and/or coexisting illnesses) are often considered unfit for chemotherapy; other patients may be unable or unwilling to endure the toxicity or inconvenience of chemotherapy. These patient groups may benefit from novel, relatively nontoxic treatment modalities. Gefitinib ("Iressa", ZD1839) 250 mg day(-1) is well tolerated and has proven antitumour and symptom improvement activity in patients with previously treated NSCLC. Phase II trials (IDEAL 1 and 2) of gefitinib in advanced/metastatic NSCLC included 70 out of 425 (16.5%) patients with PS > or =2, and their response rate, clinical benefit rate and rates of adverse events were similar to those of the overall trial population. In addition, many patients with advanced/metastatic NSCLC with poor PS or advanced age have received gefitinib 250 mg day(-1) in an Expanded Access Programme (EAP). Observations from the EAP support those of IDEAL 1 and 2, and indicate that gefitinib 250 mg day(-1) warrants further investigation in these patient groups.
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PMID:Lessons from the ("Iressa" Expanded Access Programme: gefitinib in special non-small-cell lung cancer patient populations. 1466 Oct 49

Lung cancer is one of the most common cancers and its associated mortality continues to rise in Japan. The lung cancer cure rate is still very low. To improve the survival of patients with lung cancer, well-designed and well-conducted clinical trials are essential. Several Japanese study groups have been conducting clinical trials for lung cancer. However, most randomized phase III studies were conducted by the Japan Clinical Oncology Group (JCOG), the West Japan Thoracic Oncology Group, and pharmaceutical companies supporting temporarily organized groups. In the past decade, the quality of Japanese clinical studies has improved tremendously. The results of JCOG9511 have recently been reported; and demonstrated that treatment with irinotecan/cisplatin significantly improved patient survival in extensive-stage small-cell lung cancer over standard etoposide/cisplatin, with less myelosuppression. A randomized phase II study using gefitinib (ZD1839; Iressa) for non-small-cell lung cancer was also recently reported and showed a high response rate against platinum-refractory lung cancer, especially in adenocarcinoma and in females. A 4-arm multicenter, randomized cooperative phase III study for advanced non-small-cell lung cancer is currently underway.
Clin Lung Cancer 2002 May
PMID:Results of recent Japanese clinical trials in lung cancer. 1466 31

We present a series of cases that illustrate potential benefits of the targeted agent gefitinib for patients with advanced and heavily pretreated non-small-cell lung cancer (NSCLC). In 2 phase II clinical trials, 250 mg/day of gefitinib produced objective tumor response rates of 18% and 11%, with excellent tolerance in patients with advanced NSCLC who had previously received standard chemotherapy. Treatment with gefitinib also led to improvements in disease-related symptoms in approximately 40% of cases. Gefitinib is one of a class of agents that selectively inhibit the epidermal growth factor receptor-tyrosine kinase, which is aberrantly activated in many human solid tumors. Gefitinib treatment resulted in objective radiographic regressions of tumor and symptom improvement in patients with advanced, heavily pretreated NSCLC in clinical trials and in the Expanded Access Program. This series illustrates that the benefits of gefitinib are not limited to patients selected for clinical trial participation but can be generalized to the broader population of patients with NSCLC.
Clin Lung Cancer 2003 Nov
PMID:Antitumor activity and tolerability of gefitinib in patients with non-small-cell lung cancer treated in an expanded access program. 1466 75

Non-small-cell lung cancer represents a growing global burden and remains a therapeutic challenge. Only small improvements in survival have been made with standard chemotherapeutic approaches to advanced disease in recent history. Novel biologic targeted therapies offer the potential of improving patient management and treatment outcomes in non-small-cell lung cancer. Prominent among these novel agents are the HER1/epithelial growth factor receptor (EGFR) inhibitors. One of these agents, gefitinib (Iressa), is already approved for use in advanced, refractory non-small-cell lung cancer. Erlotinib (Tarceva) is a promising HER1/EGFR inhibitor in phase III evaluation as first-line therapy combined with chemotherapy and as second-/third-line monotherapy in advanced non-small-cell lung cancer. In addition, erlotinib is being evaluated in combination with the angiogenesis inhibitor bevacizumab (Avastin), a strategy combining two new modalities in cancer treatment. Results of these trials will provide important information on optimal use of these new targeted therapies and may offer the promise of improving the treatment of non-small-cell lung cancer.
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PMID:Targeting the HER1/EGFR receptor to improve outcomes in non-small-cell lung cancer. 1468 17

Rash is a class effect of HER1/epidermal growth factor receptor (EGFR)-targeted agents, and has occurred with high frequency and in a dose-dependent manner in clinical trials of these agents in cancer patients. Analysis of phase II trials of erlotinib (Tarceva) in non-small-cell lung cancer, head and neck cancer, and ovarian cancer shows a significant association between rash severity and objective tumor response. Rash severity was highly significantly associated with survival in patients with non-small-cell lung cancer receiving erlotinib; median survival in patients with no rash was 46.5 days, compared with 257 days in those with grade 1 rash (P < .0001) and 597 days in those with grade 2/3 rash (P < .0001). Similarly, for the combined non-small-cell lung cancer, head and neck cancer, and ovarian cancer studies, median survival in patients with no rash was 103 days, compared with 191 days in those with grade 1 rash (P = .0001) and 266 days in those with grade 2/3/4 rash (P = .0001). Similar findings have been made with cetuximab (Erbitux) and in some settings with gefitinib (Iressa). The strong association of rash severity with response/survival suggests that rash may serve as a marker of response to erlotinib treatment and may be used to guide treatment to obtain optimal response. Dosing erlotinib at the maximum tolerated dose, which is associated with more frequent and more severe rash, may improve response rates and survival durations. Further study of the potentially important association between rash and outcome of treatment with EGFR-targeted agents is needed.
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PMID:Can rash associated with HER1/EGFR inhibition be used as a marker of treatment outcome? 1468 20

Symptom monitoring and quality-of-life (QOL) evaluation in lung cancer patients might improve care. Brief, valid, and responsive tools are available to measure symptoms and their effect on QOL. Instruments available for use in lung cancer patients can be classified into 3 categories: generic, cancer-specific, and lung cancer symptom-specific. These instruments might assist clinicians in assessing and interpreting treatment outcomes from the patient perspective. They also can assist in treatment decision making, symptom palliation, and they might even be prognostic of survival. Over the past 20 years, these brief evaluations have been used in clinical trials to evaluate patient-reported outcomes. Now, with the advent of less toxic, targeted molecular therapies such as gefitinib (Iressa) in non-small-cell lung cancer, these instruments' value in showing symptomatic improvement from tumor control or regression might be further enhanced. To date, however, such assessments are not widely implemented in routine clinical practice. To better understand benefits of such assessments, we review existing evidence surrounding the instruments' use, evaluate their success, and highlight recent developments. We hope to encourage clinicians to incorporate these evaluations in clinical practice.
Clin Lung Cancer 2002 Nov
PMID:The validity and clinical utility of symptom monitoring in advanced lung cancer: a literature review. 1470 64

One year has passed since the launch of a new molecular targeted agent, Iressa (generic name: Gefitinib), in Japan ahead of other countries in the world. Gefitinib is the first selective Epidermal Growth Factor Receptor (EGFR) tyrosine kinase inhibitor. Gefitinib was investigated clinically by a single dose ascending study and 3-day multiple dosing study in male volunteers in the UK initially. On confirmation of tolerability by those studies, 4 Phase I studies were conducted in patients with solid tumours generally known to over-express EGFR, with a result of 250 mg or 500 mg (oral administration) decided to be chosen as the recommended dose for Phase II studies. A Phase II study was then conducted in 9 countries including European countries, Australia, and Japan, using once daily oral dosing regimen. In this study gefitinib demonstrated response rate of 18.4% (19/103), and disease control rate of 54.4% (56/103) in advanced non-small cell lung cancer patients (with 1 or 2 previous chemotherapy regimens) at a dose level of 250 mg/day. Symptom improvement rate, which was determined using lung cancer sub-scale (LCS) for QOL assessment, was 40.3% (27/67), and median time to symptom improvement was 8 days (on the initial assessment). In 3 months after the launch, 39 lung injury deaths of patients were reported including deaths attributed to interstitial pneumonia, which was covered broadly by mass media. It is, however, considered that development of Iressa, the first EGFR tyrosine kinase inhibitor showing effects on solid tumours, for clinical use through assiduous researches on molecular targeted agents has truly great significance. This paper gives an overview covering development history to date, clinical study results, and post-launch safety reports.
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PMID:[Development of novel molecular targeted drug, "Iressa", for the treatment of malignant diseases--its basic and clinical studies]. 1471 82


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