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)

Aging society is coming now, the ratio of elderly patients among all lung cancer patients has currently been increasing. It is necessary for elderly patients who are under-represented in clinical trials to study their suitable regimen. Thus, phase II and III clinical trials have been performed specifically for elderly non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) patients all over the world. As for single agent chemotherapy, there is a strong rationale for docetaxel and vinorelbine in elderly patients with advanced NSCLC. Recently, there are phase I and II clinical trial for CPT-11 monotherapy, and gefitinib and TS-1 are reasonable options for elderly patients. Alimta is tolerable for elderly, and subset analysis is performed for the elderly with recurrent NSCLC. As platinum-based chemotherapy, there are several elderly subset analyses and JCOG 0207, which is a phase III trial now in progress comparing weekly cisplatin+weekly docetaxel and weekly docetaxel. In SCLC, there is no evidence of single agent chemotherapy but combination chemotherapy such as carboplatin+etoposide is recommended. A phase III study of carboplatin+etoposide versus amrubicin under way. These studies should aim to optimize several agents for elderly patients and prolong survival, palliative care.
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PMID:[Lung cancer]. 1735 26

The pemetrexed (Alimta) is a new generation antifolate prescribed in the treatment of mesothelioma in association with cisplatin and in the 2nd line treatment of locally advanced or metastatic non-small lung cancer. Pemetrexed is an original molecule, different from the other antifolates. On the opposite methotrexate, pemetrexed inhibits several enzymes involved in the synthesis of purines and pyrimidines, in particular thymidylate synthase, dihydrofolate reductase, glycinamide ribonucleotide formyltransferase and 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase. Pemetrexed is transported in cells by three receptors, which make easier its cellular penetration. On the other hand, the polyglutamation of the product by the folylpolyglutamate synthetase increases considerably its activity notably towards the thymidylate synthase. Finally, unlike methotrexate, pemetrexed presents an atypical effect on cellular synchronisation. The wide spectre of activity of pemetrexed confers it a therapeutic advantage with regard to the other antifolates specific of one or other one enzymes. The clinical results show an anti-tumoral activity against non-small lung cancer and in mesothelioma and recently towards other solid tumours, in particular in head an neck, colon and mammary cancers.
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PMID:[Pemetrexed: from preclinic to clinic]. 1784 83

Vandetanib is a novel, orally available inhibitor of different intracellular signaling pathways involved in tumor growth, progression, and angiogenesis: vascular endothelial growth factor receptor-2, epidermal growth factor receptor, and REarranged during Transfection tyrosine kinase activity. Phase I clinical trials have shown that vandetanib is well tolerated as a single agent at daily doses < or =300 mg. In the phase II setting, negative results were observed with vandetanib in small cell lung cancer, metastatic breast cancer, and multiple myeloma. In contrast, three randomized phase II studies showed that vandetanib prolonged the progression-free survival (PFS) time of patients with non-small cell lung cancer (NSCLC) as a single agent when compared with gefitinib or when added to chemotherapy. Rash, diarrhea, hypertension, fatigue, and asymptomatic QTc prolongation were the most common adverse events. Antitumor activity was also observed in medullary thyroid cancer. Four randomized phase III clinical trials in NSCLC are exploring the efficacy of vandetanib in combination with docetaxel, the Zactima in cOmbination with Docetaxel In non-small cell lung Cancer (ZODIAC) trial, or with pemetrexed, the Zactima Efficacy with Alimta in Lung cancer (ZEAL) trial, or as a single agent, the Zactima Efficacy when Studied versus Tarceva (ZEST) and the Zactima Efficacy trial for NSCLC Patients with History of EGFR-TKI chemo-Resistance (ZEPHYR) trials. Based on a press release by the sponsor of these trials, the PFS time was longer with vandetanib in the ZODIAC and ZEAL trials; the ZEST trial was negative for its primary superiority analysis, but was successful according to a preplanned noninferiority analysis of PFS. Ongoing phase II and III clinical trials will better define the appropriate schedule, the optimal setting of evaluation, and the safety of long-term use of vandetanib.
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PMID:Vandetanib (ZD6474), a dual inhibitor of vascular endothelial growth factor receptor (VEGFR) and epidermal growth factor receptor (EGFR) tyrosine kinases: current status and future directions. 1934 11

Cell-monolayer-based assays for chemotherapeutic drug discovery have proven to be highly artificial compared with physiological systems. The objective of this study was to culture cancer cells in a simple 3-dimensional (3D) collagen gel model to study the antiproliferative activity of known lung cancer drugs. The validity of our 3D model was tested by measuring the activity of 10 lung cancer drugs (Paclitaxel, Alimta, Zactima, Doxorubicin, Vinorelbine, Gemcitabine, 17AAg, Cisplatin, and 2 experimental drugs from the University of Kansas [KU174 and KU363]) in 2 lung cancer cell lines (A549 and H358) and comparing the activity in a traditional 2-dimensional (2D) in vitro cellular assay. Both potency and efficacy of these drugs were calculated to evaluate the activity of the drugs. Our results demonstrate that the activity of these drugs showed significant differences when tested in 3D cultures, which varied with individual drugs and the cell line used for testing. For example, the cytotoxicity of Paclitaxel, KU174, Alimta, Zacitma, Doxorubicin, Vinorelbine, KU363, and 17AAg was significantly changed when tested in the 3D model, whereas the potency of Cisplatin and Gemcitabine in H358 cell line remained unaffected. A similar pattern, with some differences, was observed in A549 cells and is discussed in detail in this article. The observed differences in potency and efficacy of the cancer drugs in 3D models suggest that the biological implications of screening configurations should be taken into account to select superior cancer drug candidates in preclinical studies.
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PMID:Activity of anticancer agents in a three-dimensional cell culture model. 2066 35


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