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 past two decades, clinical research has focused on developing chemotherapeutic regimens that effectively prolong survival and provide palliation for patients with non-small-cell lung cancer (NSCLC). In the mid-to late-1990s, several new agents emerged from clinical development and demonstrated activity against this disease, including the novel antimetabolite gemcitabine. Gemcitabine is one of the most active agents for the treatment of NSCLC. When combined with a platinum analog, gemcitabine produces the best progression-free survival outcome of any platinum-based regimen in first-line advanced NSCLC treatment setting. On the basis of its excellent antitumor activity and favorable toxicity profile, gemcitabine has been approved for the first-line treatment of locally advanced or metastatic NSCLC.
Lung Cancer 2005 Oct
PMID:A ten-year review of progress in the treatment of non-small-cell lung cancer with gemcitabine. 1629 27

Gemcitabine plus carboplatin is a widely used regimen for the treatment of advanced non-small-cell lung cancer (NSCLC). This two drug combination is effective, with a favorable safety profile, and is well tolerated in the outpatient setting. Gemcitabine/carboplatin prolongs survival compared with gemcitabine alone, but with greater hematological toxicity. The combination regimen appears to be superior to or equally effective as other regimens including mitomycin, ifosfamide and cisplatin (MIC), cisplatin/vinblastine, gemcitabine/paclitaxel, paclitaxel/carboplatin and gemcitabine/cisplatin. Gemcitabine combined with carboplatin is associated with more hematological toxicity, but the incidence of non-hematological toxicity is often significantly lower. Gemcitabine/carboplatin also improves patient quality of life, supporting its use in treating patients with advanced NSCLC in the outpatient setting.
Lung Cancer 2005 Oct
PMID:The development of gemcitabine and carboplatin in the treatment of non-small-cell lung cancer. 1629 32

Gemcitabine is a purine analog with known activity in many solid tumors, namely lung, breast, pancreatic, genitourinary and head/neck cancers. Cardiac toxicity is a rare event and only one report previously described atrial fibrillation (AF) as a consequence of gemcitabine infusion. We report two cases of women suffering from lung cancer who were treated with gemcitabine. Both patients were admitted to hospital for paroxysmal AF occurring 12-24 h after the infusion of the drug. In the first case a sinus rhythm was spontaneously repristinated when AF occurred for the first time, while the second episode required an anti-arrhythmic drug to interrupt the dysrhythmia. In the second case, the patient had to be treated with digitalis glycoside to control the ventricular response without attaining a sinus rhythm. We could not recognize any other precipitating factor beyond the infusion of gemcitabine as a cause for the arrhythmia. Both cases were treated with gemcitabine for lung cancer and we observed the appearance of AF less than 24 h after drug administration. We assume that 2',2'-difluorodeoxyuridine, an active metabolite of gemcitabine, could be responsible for the toxic effect. We conclude that AF is an unusual, but potentially dangerous, side-effect of gemcitabine infusion. The arrhythmia should be suspected whenever patients complain of dyspnea and palpitations beginning 12-24 h after treatment. In these cases, the treatment of AF consists of anti-arrhythmic drugs in order to repristinate a sinus rhythm or control the heart rate.
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PMID:Gemcitabine and atrial fibrillation: a rare manifestation of chemotherapy toxicity. 1652 Jun 66

Gemcitabine, a pyrimidine nucleoside antimetabolite, is one of the most promising new cytotoxic agents. The drug has shown activity in a variety of solid tumors, but appears to be most active in the treatment of non-small cell lung cancer. In this disease, several Italian investigators have evaluated gemcitabine in phase II and III clinical trials. Due to preclinical synergism with cisplatin, the Italian Lung Cancer Project played an important role to assess the efficacy and activity of the gemcitabine-cisplatin combination along with the best doses and schedule to adopt, thus leading to gemcitabine approval for first line treatment of advanced non-small cell lung cancer. Several Italian studies have also investigated gemcitabine non-platinum based combinations, gemcitabine in third generation platinum-based triplets and gemcitabine as second line therapy, but all these studies led to conflicting and inconclusive results. The low toxicity profile makes the drug a valid option for unfit and elderly patients. The Multicenter Italian Lung Cancer in the Elderly Study was a phase III randomized trial conducted in elderly patients with advanced non-small cell lung cancer that showed that single agent gemcitabine is at least as effective as either single agent vinorelbine or the combination of gemcitabine and vinorelbine. In the neoadjuvant treatment of stage III disease, a number of phase II studies with third generation platinum-based doublets or triplets have been conducted by Italian investigators with encouraging results. Current clinical trials are addressing the role of gemcitabine in combination with new targeted therapies. Future studies should be designed in order to identify subgroups of patients who are more likely to benefit from gemcitabine chemotherapy.
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PMID:Development of gemcitabine in non-small cell lung cancer: the Italian contribution. 1680 61

The lung cancer global incidence has regularly increased during the last decades. Non Small Cell Lung Cancer (NSCLC) accounts for approximately 80% of all lung tumors. Different schedules including cisplatin plus gemcitabine or vinorelbine or paclitaxel or docetaxel or irinotecan showed advantages in terms of response rate, toxicity and quality of life, but little improvement in terms of survival. Some advantage was documented in favour of the combination including cisplatin plus a new drug versus monochemotherapy with new drugs. The large phase III studies performed with doublets containing new drugs and platinum are not free of criticism but in summary the research involving more than 3000 patients failed to indicate a standard regimen. With the aim of strengthen the phase III studies results, a meta-analysis tested the survival outcomes of published randomized trials, analysing the effects of the combination of gemcitabine and platinum compounds versus any platinum-based regimens. Gemcitabine-platinum combinations appear to offer a statistically significant superior efficacy in terms of overall survival and progression free survival as compared to other platinum-based regimens. Considering the palliative role of chemotherapy in advanced NSCLC and in order to reduce toxicity, not cisplatin-containing regimens were investigated. The results support the suggestion from the last ASCO guidelines: first-line chemotherapy of advanced NSCLC should be a two-drug combination regimen and not platin-based chemotherapy may be used as alternative to platinum-based regimens. The new frontier is represented by pharmacogenomic. The potential benefits of the pharmacogenomic approach lay in the possibility of predicting the patient chemotherapy response developing customized chemotherapeutic combinations and limiting severe side effects.
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PMID:First line chemotherapy in advanced or metastatic NSCLC. 1680 66

Gemcitabine, a novel nucleoside analogue, has shown broad clinical activity in a variety of malignant tumors and is currently used for the treatments of non-small-cell lung cancer and pancreatic cancer in Japan. Based on the clinical results obtained in the early clinical trials in other locates, the safety profile was also established. Recently, the clinical usefulness of gemcitabine against advanced biliary tract cancer was approved in Japan. This means an important effective drug was developed against a well-known drug-refractory malignant neoplasm in Japan.
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PMID:[Gemcitabine is an effective single agent for the treatment of advanced biliary tract cancer]. 1696 42

We tested whether zoledronic acid, a biphosphonate with proposed apoptotic activity, augmented the cytotoxicity of cisplatin and/or gemcitabine in A549 lung cancer cell line. This cell line was subjected to different concentrations of the above chemotherapeutic agents and zoledronic acid. Cytotoxicity was assessed by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrasodium bromide) assay. Particularly, zoledronic acid in 100 micromolar (microM) concentration augmented the cytotoxicity by cisplatin 1microg/ml from 25% to 70% (Z=3.22, P=0.0072). A significant portion of cells underwent apoptosis with or without zoledronic acid, but more so with the combination treatment as assessed by an Annexin V-FITC apoptosis detection kit. However, 100microM zoledronic acid showed 50% cytotoxicity on its own, but failed to improve cytotoxicity by Gemcitabine. Thus, we show for the first time in a lung cancer cell line that zoledronic acid bears cytotoxic potential on its own and in conjunction with cisplatin. The clinical potential of this finding should be further studied.
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PMID:Cisplatin cytotoxicity is enhanced with zoledronic acid in A549 lung cancer cell line: preliminary results of an in vitro study. 1741 95

Five-year survival for non-small cell lung cancer is 15%. Gemcitabine is a nucleoside analogue that inhibits ribonucleotide reductase and interferes with DNA replication. In this study, we sought to compare short versus continuous infusion gemcitabine in an in vitro bioreactor system using pharmacokinetic-guided dosing. Gemcitabine was infused over either 0.5 or 2.5h to produce concentration-time profiles that mimic those measured in biological samples (i.e., patient plasma). The effects of gemcitabine on the growth and survival of H2009 cells were examined using trypan blue staining, cell cycle analysis, TUNEL assay, and clonogenic assay. Data were analyzed with two ways analysis of variance. Maximum gemcitabine (Cmax) concentrations during the short infusion were 51.2+/-10.4 microM and for the continuous, 14.8+/-2.93 microM. Steady-state concentrations during the continuous infusions were 14.9+/-2.90 microM. Gemcitabine treatment resulted in a decrease for G1 fraction relative to controls. G2/M, subG1 and TUNEL were higher following gemcitabine relative to controls. Survival was approximately 20-fold higher following the short infusion compared with the continuous infusion (p = 0.0085). In conclusion, gemcitabine infused by this novel method induced apoptosis after both the short and continuous infusions, and long-term survival was significantly diminished following continuous compared with the short infusion.
Lung Cancer 2007 Nov
PMID:Short versus continuous gemcitabine treatment of non-small cell lung cancer in an in vitro cell culture bioreactor system. 1765 59

The combination of gemcitabine and cisplatin is one of the most active chemotherapy regimens against non-small cell lung cancer (NSCLC). This study was designed to evaluate the efficacy and safety of gemcitabine combined with cisplatin in a 3-week cycle regimen for patients with operable, early stage NSCLC. Gemcitabine at a dose of 1000 mg/m(2) on days 1 and 8 of each 21-day cycle for 3 cycles, followed by cisplatin at a dose of 75 mg/m(2) on day 1 was administered to patients with previously untreated, operable, early stage (IB-IIIA) NSCLC. A total of 47 patients (46 male, mean age 56.0+/-8.0 years) who met the eligibility criteria were enrolled. The pathological complete response rate was 5.3% of operated patients and 4.3% of total patients. At visit 4, 57.1% of the patients had partial response, 38.1%, stable disease and 4.8%, progressive disease. The main toxicities - leukopenia, neutropenia and thrombocytopenia - were usually clinically asymptomatic and did not require hospitalization. Non-hematological toxicities were minimal and manageable. Disease free and 12-month overall survival rates were over 70% and 80%, respectively. This study demonstrates that the administration of gemcitabine and cisplatin combination for 3 cycles is effective and tolerable for patients with operable, early stage NSCLC. Low toxicity profile and promising survival outcome suggest that this regimen has an encouraging activity in this subset of patients.
Lung Cancer 2007 Nov
PMID:Gemcitabine and cisplatin as neo-adjuvant chemotherapy for non-small cell lung cancer: a phase II study. 1768 27

Gemcitabine, 2',2'-difluoro-2'-deoxycytidine (dFdC) is a pyrimidine antimetabolite employed against several human malignancies. It undergoes intracellular activation to the pharmacologically active triphosphate form (dFdCTP) and metabolic inactivation to the metabolite 2',2'-difluorodeoxyuridine (dFdU). In order to investigate the human plasma pharmacokinetics of dFdC and dFdU, we developed and validated an HPLC-MS/MS method, adding 2'-deoxycytidine as internal standard and simply precipitating the protein with acetonitrile. The method requires a small sample (125 microl), and it is rapid and selective, allowing good resolution of peaks from the plasma matrix in only 7 min. It is sensitive, precise and accurate, with overall precision, expressed as CV%, always less than 10.0% for both analytes and high recovery: > or = 80%. The limits of detection for dFdC and dFdU were 0.1 and 1.1 ng/ml, but considering the high concentrations in the plasma of patients investigated, we set the limit of quantitation at 20 ng/ml (0.08 microM) for dFdC and 250 ng/ml for dFdU, and validated the assay up to the dFdC concentration of 6.0 microg/ml (22.8 microM). The method was successfully used to study the drug pharmacokinetics in patients with advanced non-small-cell lung cancer in a phase II trial with gemcitabine administered as a fixed dose-rate infusion.
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PMID:Simultaneous determination of gemcitabine and its main metabolite, dFdU, in plasma of patients with advanced non-small-cell lung cancer by high-performance liquid chromatography-tandem mass spectrometry. 1794 Nov 28


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