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)

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

Erlotinib (Tarceva) is an orally available selective small-molecule inhibitor of HER1/EGFR tyrosine kinase with a 50% inhibitory concentration of 2 nM for purified tyrosine kinase. This agent has been shown to produce stasis or regression of tumor growth in human cancer xenograft models, including non-small-cell lung cancer models. Ongoing preclinical investigations indicate that inhibition of the MAPK and Atk signaling pathways downstream of HER1/EGFR may be required for optimal antitumor effects. Erlotinib exhibits inhibition of MAPK and Atk kinases at concentrations higher than those required for HER1/EGFR tyrosine kinase inhibition; such findings suggest that maximal inhibition of HER1/EGFR, requiring high erlotinib doses, is necessary for optimum antitumor activity. These considerations are supported by tumor models, including non-small-cell lung cancer models, showing dose-related antitumor effects up to high doses of erlotinib. Erlotinib exhibits additive antitumor effects when combined with chemotherapeutic agents (cisplatin, doxorubicin, paclitaxel, gemcitabine [Gemzar], and capecitabine [Xeloda]), radiation therapy, and other targeted agents (e.g., bevacizumab [Avastin]). Recent studies indicate that erlotinib inhibits the EGFRvIII mutant at concentrations higher than those required for inhibition of wild-type receptor. Ongoing investigation will help to determine optimal dosing and dose frequency of erlotinib in various cancers in the clinical setting.
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PMID:Erlotinib: preclinical investigations. 1468 18

In phase I trials in healthy volunteers and patients with refractory cancers, erlotinib (Tarceva) was well tolerated and showed activity against non-small-cell lung cancer and other tumors. The dose identified for further clinical development was 150 mg/d; at this dose, erlotinib achieves high exposure, with maximum concentrations greater than 2,000 ng/mL and 24-hour area under the concentration-time cure greater than 35,000 ng.h/L. In a phase II trial in 57 patients with previously treated advanced non-small-cell lung cancer, erlotinib treatment produced an objective response rate of 12.3% and a stable disease rate of 38.6%, with median duration of response of 19.6 weeks; median overall survival was 8.4 months and 1-year survival was 40%, with 9 patients remaining alive over follow-up of greater than 18 months. No grade 4 toxicity was observed, and grade 3 toxicity was minimal. In an ongoing phase II trial in bronchioloalveolar carcinoma, erlotinib treatment has produced objective response in 26% of 50 evaluable patients, with median duration of response not yet having been reached. An ongoing phase II trial is examining the combination of erlotinib with the angiogenesis inhibitor bevacizumab (Avastin) in previously treated non-small-cell lung cancer; phase I evaluation revealed no dose-limiting toxicities at tested doses and provided evidence of antitumor activity. Two phase III trials are examining erlotinib in combination with carboplatin (Paraplatin)/paclitaxel (the TRIBUTE trial) or cisplatin/gemcitabine (Gemzar) (the TALENT trial) as first-line treatment in advanced non-small-cell lung cancer. The phase III BR.21 trial is assessing erlotinib monotherapy in advanced refractory non-small-cell lung cancer. Results of these phase II trials will soon be available.
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PMID:Clinical experience with the HER1/EGFR tyrosine kinase inhibitor erlotinib. 1468 19

In Westernised countries, colorectal cancer (CRC) is second only to lung cancer as a cause of death from malignancy, with only 60% of patients alive at 5 years. In Stage II/III CRC, where the standard treatment is 5-fluorouracil (5-FU)/leucovorin, a recent clinical trial has shown that with the addition of oxaliplatin, fewer patients have relapsed or died at 40 months follow-up. The benefit was more pronounced in patients with Stage III than II CRC, and the addition of oxaliplatin to 5-FU/leucovorin should be considered in Stage III CRC. In metastatic CRC, where the standard treatment is 5-FU/leucovorin/irinotecan, a recent clinical trial has shown that the addition of bevacizumab, a mAb, to vascular endothelial growth factor, prolonged progression-free and overall survival. Bevacizumab is likely to become part of the standard therapy for metastatic CRC.
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PMID:Which drug combination for colorectal cancer? 1557 79

The field of cancer research has seen a marked shift in the past decade towards the exploration and development of non-conventional antitumour agents. One of the most widely studied approaches to therapy during this period has been that of antiangiogenesis. The published clinical trials and subsequent FDA approval (in February 2004) of the anti-vascular endothelial growth factor (VEGF) monoclonal antibody bevacizumab (Avastin, Genentech) for the treatment of colorectal cancer marked a milestone for antiangiogenesis therapy. Currently, preclinical and clinical research involving therapeutic targeting of VEGF and other mediators of angiogenesis continues in multiple tumour types. In addition to colorectal cancer, angiogenesis inhibitors are being investigated in the treatment of renal cell carcinoma, head and neck carcinoma, lung cancer, breast cancer, prostate cancer, and a variety of haematological malignancies. This article will discuss the background of antiangiogenesis research, preclinical and clinical data relating to the use of bevacizumab in the treatment of colorectal cancer, other completed clinical trials involving antiangiogenesis agents, and the potential future utility of these agents in the treatment of malignancy.
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PMID:Angiogenesis inhibitors in the treatment of cancer. 1608 56

Platinum-based chemotherapy offers a modest survival advantage over best supportive care in chemotherapy-naive patients with a good performance status and advanced/metastatic non-small-cell lung cancer (NSCLC). Despite the survival benefit associated with first-line chemotherapy, the majority of patients will experience relapse or disease progression. In clinicalpractice, an increasing number of patients maintain a good performance status after first-line treatment and are eligible for further treatments. Docetaxel (Taxotere) at 75 mg/m2 given once every 3 weeks has been the standard of care for second-line chemotherapy since the year 2000. Pemetrexed (Alimta) is a novel multitargeted antifolate agent with single-agent activity in first- and second-line treatment of NSCLC. A large phase 111 study comparing docetaxel to pemetrexed in second-line therapy demonstrated that pemetrexed is equally active and less toxic than docetaxel. Based on these results, pemetrexed is a reasonable second-line chemotherapy option for patients with recurrent, advanced NSCLC. Progress made in the field of molecular biology has led to the identification of drugs active against specific cellular targets. Gefitinib (Iressa) and erlotinib (Tarceva) are both orally active tyrosine kinase inhibitors of the epidermal growth factor receptor. Phase II and III trials have demonstrated that these agents are active particularly in a subgroup of patients with specific biologic characteristics. Both drugs have been approved for the treatment of pretreated NSCLC. Other drugs, such as cetuximab (Erbitux) and bevacizumab (Avastin) have shown promising activity in NSCLC and are currently being tested in clinical trials.
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PMID:Perspectives on salvage therapy for non-small-cell lung cancer. 1613 Oct 43

Neoadjuvant chemotherapy (NACT) is a term originally used to describe the administration of chemotherapy preoperatively before surgery. The original rationale for administering NACT or so-called induction chemotherapy to shrink or downstage a locally advanced tumour, and thereby facilitate more effective local treatment with surgery or radiotherapy, has been extended with the introduction of more effective combinations of chemotherapy to include reducing the risks of metastatic disease. It seems logical that survival could be lengthened, or organ preservation rates increased in resectable tumours by NACT. In rectal cancer NACT is being increasingly used in locally advanced and nonmetastatic unresectable tumours. Randomised studies in advanced colorectal cancer show high response rates to combination cytotoxic therapy. This evidence of efficacy coupled with the introduction of novel molecular targeted therapies (such as Bevacizumab and Cetuximab), and long waiting times for radiotherapy have rekindled an interest in delivering NACT in locally advanced rectal cancer. In contrast, this enthusiasm is currently waning in other sites such as head and neck and nasopharynx cancer where traditionally NACT has been used. So, is NACT in rectal cancer a real advance or just history repeating itself? In this review, we aimed to explore the advantages and disadvantages of the separate approaches of neoadjuvant, concurrent and consolidation chemotherapy in locally advanced rectal cancer, drawing on theoretical principles, preclinical studies and clinical experience both in rectal cancer and other disease sites. Neoadjuvant chemotherapy may improve outcome in terms of disease-free or overall survival in selected groups in some disease sites, but this strategy has not been shown to be associated with better outcomes than postoperative adjuvant chemotherapy. In particular, there is insufficient data in rectal cancer. The evidence for benefit is strongest when NACT is administered before surgical resection. In contrast, the data in favour of NACT before radiation or chemoradiation (CRT) is inconclusive, despite the suggestion that response to induction chemotherapy can predict response to subsequent radiotherapy. The observation that spectacular responses to chemotherapy before radical radiotherapy did not result in improved survival, was noted 25 years ago. However, multiple trials in head and neck cancer, nasopharyngeal cancer, non-small-cell lung cancer, small-cell lung cancer and cervical cancer do not support the routine use of NACT either as an alternative, or as additional benefit to CRT. The addition of NACT does not appear to enhance local control over concurrent CRT or radiotherapy alone. Neoadjuvant chemotherapy before CRT or radiation should be used with caution, and only in the context of clinical trials. The evidence base suggests that concurrent CRT with early positioning of radiotherapy appears the best option for patients with locally advanced rectal cancer and in all disease sites where radiation is the primary local therapy.
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PMID:Neoadjuvant chemotherapy prior to preoperative chemoradiation or radiation in rectal cancer: should we be more cautious? 1646 72

Non-small cell lung cancer (NSCLC) is the leading cause of cancer death in the United States and throughout the world. This is largely because more than half of lung cancer cases present as metastatic disease, making local therapy for cure impossible. The last decade has seen significant improvement in first-line treatment of NSCLC, including the use of new chemotherapeutic agents with more effective therapeutic profiles. However, standard cytotoxic regimens are still limited and it remains critical to better understand and develop new treatment options for refractory disease. This has included some new second-line therapeutic approaches and has led to a focus on molecular targeted therapy, including agents that block the epidermal growth factor receptor (EGFR) or angiogenesis. EGFR-targeted agents such as gefitinib, erlotinib, and cetuximab have been successfully used for NSCLC treatment, with studies reporting overall response rates of 18.4%, 8.9%, and 3.3%, respectively. Angiogenesis inhibitors such as bevacizumab and ZD6474 have also improved treatment outcome. Bevacizumab had an overall response rate of 27% when used in combination with paclitaxel and carboplatin, and ZD6474 had an overall response rate of 26% when used in combination with docetaxel. Using these compounds alone or in combination may improve the survival and quality of life of patients with lung cancer in the refractory setting.
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PMID:Use of novel second-line targeted therapies in non-small cell lung cancer. 1647 4

Lung cancer is the leading cause of cancer deaths in the USA. Despite the development of new chemotherapy regimens, the prognosis remains poor. Several studies comparing various platinum-based regimens failed to produce a significant impact in the outcomes for patients with non-small cell lung cancer and this therapeutic modality appears to be reaching a plateau. It has become clear that further advances will require the addition of agents with a different mechanism of action. Bevacizumab is the antiangiogenic agent at the most advanced stage of development in the treatment of cancer. Bevacizumab is synergistic with chemotherapy and usually well tolerated. The addition of bevacizumab to chemotherapy improved survival in patients with metastatic non-small cell lung cancer in a randomized clinical trial. Several small molecule antiangiogenic agents are in development. In this article, currently available data from clinical trials of antiangiogenic compounds in advanced non-small cell lung cancer are reviewed.
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PMID:Clinical trials of antiangiogenic therapy in non-small cell lung cancer: focus on bevacizumab and ZD6474. 1661 42

Every year in the UK, around 16,000 people die from colorectal cancer, the second commonest cause of death from cancer in the UK after lung cancer. Over half of all people with colorectal cancer eventually die of metastatic disease. While median survival has increased with optimal use of combination chemotherapy, only a small minority of patients are still alive 5 years after diagnosis of metastases. Bevacizumab (pronounced be-va-see-zoo-mab) (Avastin - Roche) and cetuximab (se-tuks-ee-mab) (Erbitux - Merck) are two new monoclonal antibodies licensed for treating patients with metastatic colorectal cancer. Here we assess their efficacy and safety.
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PMID:Bevacizumab and cetuximab for colorectal cancer. 1670 33


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