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)

The efficacy of gemcitabine containing regimens has been explored in a large number of studies presented at ASCO 2002. The activity of gemcitabine-platinum based combinations was confirmed in lung cancer and bladder cancer. In pancreatic cancer, single agent gemcitabine remains the reference treatment, but newer combinations with oxaliplatin or docetaxel show promising activity in phase II trials and are currently being evaluated in phase III. Gemcitabine has demonstrated promising activity in phase II studies in metastatic breast cancer and gynaecologic tumors; phase III trials are ongoing. Concomitant chemo-radiation using gemcitabine as a radiosensitizer have been shown to be highly effective in pancreatic and in bladder cancer and deserve further investigation. The growing interest in gemcitabine-based combinations in various tumor types together with the results presented at ASCO 2002 confirm the broad range of activity of this drug. This is a review of papers presented at ASCO 2002.
 ...
PMID:[Updates on gemcitabine at the American Society of Clinical Oncology congress (ASCO, 2002) ]. 1244 45

Around one-third of all patients with non-small cell lung cancer (NSCLC) are over the age of 70. Elderly patients tolerate chemotherapy poorly because of impaired organ function and co-morbidities. For this reason, these patients are often not considered eligible for aggressive cisplatin-based chemotherapy. A multidimensional geriatric evaluation is important to plan appropriate treatments. At present, there are no indications for adjuvant and neoadjuvant chemotherapy. Combined chemo-radiotherapy in locally advanced disease increases toxicity and seems determine no survival advantage as compared to radiation therapy alone. In advanced disease, single agent vinorelbine proves to be active and well-tolerated, and compared to best supportive care, improves survival and perhaps quality of life. Gemcitabine is active and well tolerated as well. Taxanes are in advanced phase of evaluation. A phase III randomized trial showed that polychemotherapy with gemcitabine + vinorelbine does not improve any outcome as compared to single agent chemotherapy with vinorelbine or gemcitabine. In clinical practice, single agent chemotherapy should remain the standard treatment. The choice of the drug should be based on the toxicity profile of each drug and type of co-morbid conditions. In the near future, new therapeutic strategies and biological agents could improve present results.
Lung Cancer 2002 Dec
PMID:Chemotherapy of non-small cell lung cancer in the elderly. 1246 50

Gemcitabine is used to treat solid tumours such as non small-cell lung cancer. In general, it is a well tolerated cytotoxic agent and myelosuppression is the major dose limiting side-effect. Pulmonary toxicity has been described and dyspnoea occurs in approximately 8% of patients in whom, for the majority, it is mild and reversible. But several cases of acute respiratory distress syndrome (ARDS) related to Gemcitabine treatment have been reported since 1997 and a few were fatal. We present a case of Gemcitabine toxicity in a patient treated for a lung cancer. He presented with a respiratory distress syndrome due to acute interstitial pneumonitis from which he promptly recovered with corticosteroid therapy.
 ...
PMID:[Severe interstitial pneumonitis related to Gemcitabine]. 1247 53

Intrathecal chemotherapy has been the mainstay treatment for meningeal carcinomatosis for decades. However, this has not been the case with non-small cell lung cancer (NSCLC), due to the low efficacy of the drugs that could be used before. Gemcitabine is an effective drug against NSCLC and has a structure similar to cytarabine, which has been widely used in intrathecal chemotherapy. Thus, intrathecal gemcitabine chemotherapy might prove to be suitable for leptomeningeal carcinomatosis induced by NSCLC. We herein report our experience using gemcitabine intrathecal injections in a NSCLC patient with leptomeningeal carcinomatosis.
Lung Cancer 2003 Apr
PMID:Intrathecal gemcitabine chemotherapy for non-small cell lung cancer patients with meningeal carcinomatosis--a case report. 1266 14

Gemcitabine (2',2'-difluorodeoxycytidine) is a deoxycytidine analogue that is activated by deoxycytidine kinase (dCK) to its monophosphate and subsequently to its triphosphate dFdCTP, which is incorporated into both RNA and DNA, leading to DNA damage. Multidrug resistance (MDR) is characterised by an overexpression of the membrane efflux pumps P-glycoprotein (P-gP) or multidrug resistance-associated protein (MRP). Gemcitabine was tested against human melanoma, non-small-cell lung cancer, small-cell lung cancer, epidermoid carcinoma and ovarian cancer cells with an MDR phenotype as a result of selection by drug exposure or by transfection with the mdr1 gene. These cell lines were nine- to 72-fold more sensitive to gemcitabine than their parental cell lines. The doxorubicin-resistant cells 2R120 (MRP1) and 2R160 (P-gP) were nine- and 28-fold more sensitive to gemcitabine than their parental SW1573 cells, respectively (P<0.01), which was completely reverted by 25 micro M verapamil. In 2R120 and 2R160 cells, dCK activities were seven- and four-fold higher than in SW1573, respectively, which was associated with an increased dCK mRNA and dCK protein. Inactivation by deoxycytidine deaminase was 2.9- and 2.2-fold decreased in 2R120 and 2R160, respectively. dFdCTP accumulation was similar in SW1573 and its MDR variants after 24 h exposure to 0.1 micro M gemcitabine, but dFdCTP was retained longer in 2R120 (P<0.001) and 2R160 (P<0.003) cells. 2R120 and 2R160 cells also incorporated four- and six-fold more [(3)H]gemcitabine into DNA (P<0.05), respectively. P-glycoprotein and MRP1 overexpression possibly caused a cellular stress resulting in increased gemcitabine metabolism and sensitivity, while reversal of collateral gemcitabine sensitivity by verapamil also suggests a direct relation between the presence of membrane efflux pumps and gemcitabine sensitivity.
 ...
PMID:Increased sensitivity to gemcitabine of P-glycoprotein and multidrug resistance-associated protein-overexpressing human cancer cell lines. 1279 44

Gemcitabine (2'-2'-difluorodeoxycytidine) is a recently developed pyrimidine antagonist that is structurally related to cytarabine (ara-C). When phosphorylated intracellularly, gemcitabine inhibits ribonucleotide reductase and arrests cell cycling in the S phase. Paclitaxel is a potent promoter and stabilizer of microtubule spindle formation and an inhibitor of cell cycling. In this report, we discuss 2 patients with advanced-stage non-small-cell lung cancer (NSCLC) treated with a combination of gemcitabine/paclitaxel who developed pulmonary symptoms of dyspnea and cough. Chest radiographs and computed tomography revealed diffuse pulmonary infiltrates. Bronchoscopic evaluation revealed diffuse alveolar damage with associated type II pneumocyte hyperplasia without evidence of infection or metastatic carcinoma, suggesting the development of a drug-induced pulmonary toxicity. Both cases improved with the discontinuation of gemcitabine/paclitaxel and with supportive care including steroids in one of the patients. We also review the published case reports of pneumonitis believed to be secondary to the taxanes or gemcitabine when used as single agents and a solitary case report describing pneumonitis in the setting of both a taxane and gemcitabine. Because the combination of gemcitabine/paclitaxel has demonstrated activity in NSCLC, the use of this combination is likely to increase. Clinicians caring for lung cancer patients receiving this combination should be aware of this potential pulmonary toxicity.
Clin Lung Cancer 2002 Jul
PMID:Hypersensitivity pneumonitis in advanced non-small-cell lung cancer patients receiving gemcitabine and paclitaxel: report of two cases and a review of the literature. 1465 77

A study was conducted to investigate the feasibility and acceptability of administering single-agent gemcitabine to patients with advanced non-small-cell lung cancer (NSCLC) in their own homes. Gemcitabine is an active agent in NSCLC with a good toxicity profile and lends itself to this type of investigation. A total of 24 patients were studied; as only one patient required gemcitabine to be changed from home administration to hospital administration, domiciliary gemcitabine is feasible. A total of 249 injections of gemcitabine were given, the mean number of courses being 3.5, range 1-6. The gemcitabine was given at 1000 mg m(-2) on days 1, 8 and 15, the courses being repeated every 28 days. All patients received their first course in hospital and in total 147 were given at home and only 14 in hospital on courses 2-6. Furthermore, both the patients and carers reported positively on the use of domiciliary gemcitabine and preferred it over hospital administration. There was no evidence of increasing burden to community services during the domiciliary chemotherapy. Further studies investigating this approach are warranted.
 ...
PMID:Domiciliary chemotherapy with gemcitabine is safe and acceptable to advanced non-small-cell lung cancer patients: results of a feasibility study. 1467 93

The median survival for patients with locally advanced non-small-cell lung cancer (NSCLC) remains 18 months, at best, in cooperative group efforts. Integrating new agents into the standard combined modality treatment paradigm is a daunting challenge. Gemcitabine has activity in advanced NSCLC and is a potent radiosensitizer, but preclinical trials did not delineate an optimal dose or schedule, and early attempts to graft full-dose gemcitabine (1000 mg/m2/week) onto standard radical thoracic radiation therapy (RT) were marked by significant grade 4 and 5 toxicity. More recent trials, however, have shown that attenuated doses of 150-300 mg/m2/week during radiation (XRT) are safer and potentially efficacious. Higher doses produce dose-limiting esophageal and pulmonary toxicities. Using a twice-weekly schedule, the maximum tolerated dose is 35 mg/m2. The use of 3 dimensional conformal RT may enable significant dose escalations while substantially reducing esophageal exposure and minimizing toxicity. The cooperative oncology groups are just beginning to evaluate gemcitabine in this setting. Cancer and Leukemia Group B, in a randomized phase II study, assessed combination gemcitabine and cisplatin in both the induction and radiosensitizing setting. During the induction phase, gemcitabine was given 1250 mg/m2 on days 1 and 8 every 3 weeks for 2 cycles in combination with cisplatin 80 mg/m2 every 3 weeks, and then reduced to 600 mg/m2 days 1 and 8 every 3 weeks during XRT. The overall response rate was 63% with median survival of 18.3 months and 1-year and 3-year survival rates of 68% and 28%, respectively. Radiation Therapy Oncology Group is currently spearheading a phase I study of concurrent radiation and weekly gemcitabine in combination with either weekly carboplatin or paclitaxel. Ongoing efforts will also evaluate the role of gemcitabine either alone or in combination with docetaxel in the consolidation setting after definitive chemoradiation has been completed. Whether gemcitabine in combination with radiation, with or without other agents, will ultimately prove superior to standard chemoradiation regimens remains to be determined.
Clin Lung Cancer 2003 Jan
PMID:The emerging role of gemcitabine in combination with radiation in locally advanced, unresectable non-small-cell lung cancer. 1472 Mar 36

Surgical resection remains the standard of care in early-stage non-small-cell lung cancer (NSCLC). In those patients undergoing complete surgical resection, the dominant recurrence pattern is systemic with only a minority of patients experiencing local recurrence. Unfortunately, adjuvant chemotherapy (with or without thoracic radiation therapy) has not been proven to enhance survival in resected NSCLC. Preoperative or induction therapy offers several advantages over postoperative therapy, including earlier attention to systemic micrometastatic disease and enhanced tolerance to treatment. The feasibility of this approach has been demonstrated in several phase II as well as phase III trials predominantly in stage III NSCLC but also in stage IB and II NSCLC. In proof-of-concept phase III trials, the impact preoperative therapy has on survival has not been consistent, but most trials are small in patient number, limiting the power they have in detecting small but clinically meaningful differences. Gemcitabine-containing regimens have been evaluated in several phase II trials in resectable stage III NSCLC. The overall response rate has ranged from 53%-70% with the majority of patients undergoing complete surgical resection. Toxicity has been acceptable, and the combination of cisplatin/gemcitabine is currently being evaluated as induction therapy in several phase III trials. Ongoing trials in stage I-II NSCLC are incorporating gemcitabine-containing regimens in the preoperative setting. Continued evaluation of gemcitabine-containing regimens as preoperative therapy is warranted given their level of activity and tolerability in advanced NSCLC.
Clin Lung Cancer 2003 Jan
PMID:Gemcitabine-based combinations as preoperative therapy in resectable non-small-cell lung cancer. 1472 Mar 37

Small-cell lung cancer (SCLC) accounts for 20%-25% of all new cases of lung cancer and represents the sixth most commonly diagnosed cancer in the United States. Given the tumor's systemic nature and chemoresponsiveness, chemotherapy has become the cornerstone of its management. Chemotherapy significantly prolongs survival; however, most of the patients still die within 2 years of diagnosis. Combination chemotherapy represents the treatment of choice for this disease. In the United States, cisplatin/etoposide is the regimen most frequently used for the first-line therapy of SCLC patients because of its better therapeutic index. Upon recurrence, topotecan is the Food and Drug Administration-approved treatment based on a phase III trial that showed no statistically significant differences in survival or response for topotecan compared with CAV (cyclophosphamide/doxorubicin/vincristine) but a better disease-related symptom improvement compared to baseline favoring the topoisomerase I inhibitor. Newer agents, with novel mechanisms of action, have shown activity against SCLC and are being tested in many different combinations. Among these agents, gemcitabine has attractive mechanisms of action and toxicity profile. Gemcitabine is a pyrimidine nucleoside antimetabolite, analogue to cytosine arabinoside, which through incorporation into the DNA leads to inhibition of DNA synthesis and cytotoxicity. As a single agent, gemcitabine has modest activity against SCLC. However, like with many other drugs, response rates improve when gemcitabine is used in combination regimens. Phase II and III studies of combinations with classic drugs for the management of SCLC patients such as cisplatin and/or etoposide and gemcitabine demonstrate comparable results to those of standard therapies. The gemcitabine/paclitaxel and gemcitabine/topoisomerase I inhibitor combinations are also of great interest, and preliminary results in previously treated patients are promising. The proper role of gemcitabine in the treatment of patients with SCLC awaits future testing in randomized phase III trials.
Clin Lung Cancer 2003 Jan
PMID:New agents in the treatment of small-cell lung cancer: focus on gemcitabine. 1472 Mar 38


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>