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

A number of randomized clinical trials now support the conclusion that the combined-modality regimen that includes gemcitabine (Gemzar) and cisplatin (Platinol) may improve survival in disseminated non-small-cell lung cancer. Cisplatin is considered to be the "backbone" of this combination chemotherapy due to its proven activity. The regimen of gemcitabine and cisplatin has been tested and is now considered among the most active combinations in the treatment of disseminated non-small-cell lung cancer.
 ...
PMID:Gemcitabine and cisplatin combination in early-stage non-small-cell lung cancer. 1130 47

Gemcitabine (Gemzar) has demonstrated activity in a broad range of solid tumors with good tolerance. In combined-modality therapy, gemcitabine has achieved response rates ranging between 30% and 60% in patients with non-small-cell lung cancer. Initial trials of gemcitabine and radiation showed that the fields and volume of radiation as well as the dose of gemcitabine should be managed carefully so as to optimize the radiosensitizing properties of this agent. The Cancer and Leukemia Group B conducted a phase III trial in patients with unresectable stage III non-small-cell lung cancer. A total of 187 patients were randomized to one of three cisplatin (Platinol)-based combinations (with gemcitabine, paclitaxel [Taxol], or vinorelbine [Navelbine]) as induction therapy followed by concomitant chemoradiation. At a median follow-up of 9 months, the median survival for all patients was 18 months and the median progression-free survival was 10 months. The trial demonstrated that the combination of gemcitabine and cisplatin could be administered successfully as induction therapy without affecting concurrent administration of gemcitabine/cisplatin with radiation.
 ...
PMID:Optimizing chemoradiation in locally advanced non-small-cell lung cancer. 1130 48

One of the main reasons for the increased acceptance of chemotherapy for both early and advanced non-small-cell lung cancer is the clinical availability of several new cytotoxic drugs. These less toxic, yet highly effective, new drugs not only benefit younger patients, but also offer new treatment opportunities for the elderly; advanced age alone should not preclude appropriate cytotoxic therapy. Vinorelbine (Navelbine) was the first new agent tested in randomized trials with elderly patients having advanced non-small-cell lung cancer. Results proved that vinorelbine does indeed have a survival advantage over best supportive care for these patients. Gemcitabine (Gemzar) is probably the most effective cytotoxic agent in the treatment of non-small-cell lung cancer today, showing high antitumor activity as a single agent and in combination. Moreover, it has a favorable toxicity profile. Since it can be effectively used for the palliation of tumor-related symptoms and can thus positively influence performance status, gemcitabine may be of great clinical importance in the treatment of elderly and unfit patients. Docetaxel (Taxotere) has recently become the first agent to be registered for second-line chemotherapy in non-small-cell lung cancer. This decision was based on survival advantages and clinical benefit data stemming from two randomized phase III studies. Nonetheless, chemotherapy for elderly patients continues to be a major unresolved oncologic problem. Clinical research with the new cytotoxic agents should be intensified to further define the most appropriate use for these drugs as single agents or in combination for the treatment of elderly patients.
 ...
PMID:Treatment of elderly patients with non-small-cell lung cancer. 1130 49

During the past decade, five new cytotoxic drugs have been introduced that are active against non-small-cell lung cancer (NSCLC). These agents include vinorelbine (Navelbine), paclitaxel (Taxol), docetaxel (Taxotere), gemcitabine (Gemzar), and irinotecan (CPT-11, Camptosar). Used alone, these drugs display activity comparable to cisplatin. The combination of cisplatin and one of the newer drugs produces better survival than treatment with cisplatin (Platinol) alone. Randomized studies of chemotherapy regimens that include these newer drugs have demonstrated improved survival, fewer side effects, or both, compared with earlier standard combinations such as cisplatin/vindesine or cisplatin/etoposide. Docetaxel and perhaps some of the other newer drugs are of value for patients previously treated with platinum-containing regimens. Future studies should determine whether combinations of these newer drugs are superior to cisplatin-containing regimens. Although improved survival is the most important factor in defining the best regimen in non-small-cell lung cancer, additional considerations include patient tolerability, costs of administration, and the rationale for and ability to include noncytotoxic agents (such as inhibitors of signal transduction pathwriys or angiogenesis) into the therapeutic program.
 ...
PMID:Rationale for non-platinum chemotherapy in advanced NSCLC. 1149 29

Small cell lung cancer is a chemosensitive disease; however, patients with extensive-stage disease or adverse prognostic factors are rarely cured. Gemcitabine (Gemzar; Eli Lilly and Company, Indianapolis, IN), a new agent with good tolerability, interacts synergistically with platinum agents. Carboplatin is as effective as cisplatin, but is less toxic. The London Lung Cancer Group is conducting a multicenter, open-label, randomized, phase III trial in patients with histologically or cytologically proven small cell lung cancer and extensive-stage, limited-stage but locally-advanced, or limited-stage disease with poor prognostic factors. Chemotherapy consists of 21-day cycles of gemcitabine 1,200 mg/m(2) intravenous (IV) on days 1 and 8, plus carboplatin area under the curve of 5 IV on day 1, or cisplatin 60 mg/m(2) IV on day 1 plus etoposide 120 mg/m(2) IV on day 1 and 100 mg orally on days 2 and 3. Thirty-nine patients have been randomized to gemcitabine/carboplatin and 38 to cisplatin/etoposide (23 and 22 completed treatment, with 96 and 84 cycles, respectively). Preliminary toxicity data indicate hematologic toxicity in 25% of cycles for gemcitabine/carboplatin and 16% for cisplatin/etoposide, although cisplatin/etoposide-treated patients experienced significant alopecia, nephrotoxicity, nausea and vomiting, and neutropenia. This London Lung Cancer Group trial of gemcitabine/carboplatin may define an active, safe, and acceptable treatment for patients with extensive-stage and poor-prognosis small cell lung cancer. Semin Oncol 28 (suppl 10):15-18.
 ...
PMID:Gemcitabine/carboplatin versus cisplatin/etoposide for patients with poor-prognosis small cell lung cancer: a phase III randomized trial with quality-of-life evaluation. 1151 29

Although treatment of advanced non-small-cell lung cancer has been improved with the availability of such new agents as the taxanes, topoisomerase inhibitors, vinorelbine (Navelbine), and gemcitabine (Gemzar), platinum-based combination therapy has appeared to reach a threshold of therapeutic effectiveness. A paradigm shift in approach to non-small-cell lung cancer and other tumors may be heralded by the development of agents targeting specific biologic pathways in tumor development. Such new agents include antibody epithelial growth factor receptor (EGFR) inhibitors (eg, the monoclonal antibodies trastuzumab [Herceptin] and cetuximab [IMC-C225, Erbitux]) and EGFR tyrosine kinase inhibitors (eg, ZD1839 [Iressa] and OSI-774), angiogenesis inhibitors (eg, matrix metalloproteinase inhibitors), vascular endothelial growth factor (VEGF) inhibitors (eg, monoclonal antibody to VEGF ligand and small-molecule tyrosine kinase), and signal transduction inhibitors (eg, ISIS-3521, an antisense oligonucleotide to protein kinase C-alpha). A number of these agents have entered advanced-phase clinical investigation. It is likely that targeted therapy will have applications in combination with cytotoxic chemotherapy or radiation therapy at all stages of treatment, including maintenance therapy. It is even possible that these new biologic therapies will be used together as rational combinations (based on pathologic diagnosis) for advanced non-small-cell lung cancer.
 ...
PMID:Targeted therapy in non-small-cell lung cancer. 1237 97

Several chemotherapeutic regimens have emerged in the past 5 years with the capability to improve survival and quality of life of patients with advanced non-small cell lung cancer (NSCLC). Among these treatments, the regimen of gemcitabine (Gemzar) and carboplatin (Paraplatin) has gained increasing acceptance. The combination of these two drugs was initially hampered by unacceptable platelet toxicity. However, the use of a 21-day schedule with the administration of gemcitabine on days 1 and 15 or the use of a 28-day schedule with the omission of day-15 gemcitabine has clearly been well tolerated and active. Unlike taxane based regimens, there is no need for steroid premedication, and neurotoxicity and alopecia are absent. This regimen is well tolerated and easily administered on an outpatient basis. It therefore represents an excellent "platform regimen" for the addition of new agents, particularly those associated with minimal myelotoxicity. Three-drug regimens consisting of gemcitabine/carboplatin and a taxane have been evaluated both with concurrent and sequential administration of the drugs. Trials are under way or planned for the addition of novel agents such as C225, UCN-01, PKC-alpha antisense, bexarotene, COX-2 inhibitors and other agents.
Lung Cancer 2002 Nov
PMID:Past, present, and future of gemcitabine and carboplatin regimens in advanced non-small cell lung cancer. 1243 28

Lung cancer is the most lethal malignancy in the United States. In light of its natural history, new agents with improved systemic activity are needed. Irinotecan (CPT-11, Camptosar) is a promising agent in the treatment of advanced non-small-cell and small-cell lung cancer. In subgroup analysis of a Japanese phase III trial, irinotecan or irinotecan/cisplatin demonstrated a significant survival advantage compared with standard vindesine (Eldisine)/cisplatin in advanced non-small-cell lung cancer. Similar North American phase III trials focusing on irinotecan's role in non-small-cell lung cancer are planned. Ongoing trials have also been inaugurated to corroborate the significant survival advantage reported by a Japanese phase III trial of irinotecan/cisplatin vs standard etoposide/cisplatin in extensive small-cell lung cancer. Current and planned trials in patients with non-small-cell lung cancer will investigate treatment using irinotecan in combination with gemcitabine (Gemzar), the taxanes, and other new agents, as well as with thoracic radiotherapy. Moreover, trials in small-cell lung cancer are investigating the utility of irinotecan in combination with a platinum agent when incorporated in chemoradiotherapy regimens. It is hoped that data from these and other studies will help investigators to more clearly delineate a role for irinotecan in the management of lung cancer.
 ...
PMID:The global role of irinotecan in the treatment of lung cancer: 2003 update. 1288 72

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.
 ...
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.
 ...
PMID:Clinical experience with the HER1/EGFR tyrosine kinase inhibitor erlotinib. 1468 19


<< Previous 1 2 3 4 5 Next >>