Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0684249 (lung carcinoma)
 23,830 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chemotherapy (CT) for elderly patients is becoming a standard, since the first demonstration by Gridelli and co-workers that chemotherapy (in their case Vinorelbine (VNB), single agent) is capable to produce significant survival benefits. Much less is known concerning the use of CT for unfit patients. The purpose of this phase II trial was to perform a comprehensive evaluation of activity, toxicity, and tolerability of single-agent Gemcitabine (GEM) (Gemzar) as a first-line chemotherapy for unfit patients with inoperable or recurrent non-small cell lung cancer. Patients were eligible if they had a pathological diagnosis and no previous chemotherapy; they should be younger than 76, with a performance status (ECOG-PS) equal to three; informed consent was also required. Gemcitabine was given by intravenous infusion at a weekly dose of 1250 mg/m2, 3 weeks per month, every 28 days. Treatment was given until progression, persistent toxicity, or refusal. Forty-five patients (39 males) entered the study; median age was 73 years (range 45-75); cell types were: adenocarcinoma (21), squamous (18), large cell (6). Previous surgical treatments included three lobectomies and one pneumectomy. Because of rapid clinical deterioration or consent withdrawal, six patients, registered for study, never started their treatment; other six had early chemotherapy suspension. These patients were included in the analysis, on an "intent-to-treatment" basis. The median number of chemotherapy cycles was nine (range 0-15); median dose-intensity was 75% of projected. Toxicity was mild, mainly hematological and never life threatening (only 1 grade 4 toxicity out of 325 pre-chemotherapy evaluations). Four patients obtained a partial response (9%, C.I. 1-17%) and other six patients had some tumor regression (13%, C.I. 3-23%). The estimated median time to progression was 17 weeks (quartile range: 9-24), with a median survival of 35 weeks (quartile rage: 20-51). We have found that single-agent gemcitabine represent a sufficiently safe therapeutic option in unfit patients with inoperable non-small cell carcinoma (NSCLC).
Lung Cancer 2004 Sep
PMID:Front-line weekly chemotherapy with gemcitabine for unfit patients with non-small cell lung cancer (NSCLC). 1530 78

Docetaxel and Gemcitabine are active agents in non-small cell lung carcinoma (NSCLC). They have different mechanism of action, minimal overlapping toxicity, and are easily administered on an outpatient basis. This phase II study evaluated Docetaxel administered with Gemcitabine on days 1 and 8 in a 3-week cycle, to determine its efficacy, while attempting to lower the regimen's toxicity, especially myelosuppression which can occur when Docetaxel is administered at full dose on day 1 only. Forty-three chemonaive patients, 40 evaluable, were entered in this trial between May 2001 and March 2002. Thirty-seven patients had stage IV and three patients had stage III B NSCLC, median age 58 (ages 32-78), median performance status (PS) 1 (range 0-2). They were treated with Docetaxel 36mg/m(2) and Gemcitabine 1000mg/m(2) intravenously on days 1 and 8 in a 3-week cycle. No growth factors were administered. Of 40 evaluable patients, 4 achieved partial response (10%), 25 stable disease (62.5%) and 11 progressive disease (27.5%). Median time-to-disease progression was 15 weeks. Median survival was 7.75 months. One year survival was 32.5% (13 patients). Hematologic toxicity was minimal, non-hematologic toxicity was easily treatable. Docetaxel, when given with Gemcitabine on days 1 and 8 every 3 weeks, is less myelotoxic, yet still an effective treatment for metastatic NSCLC.
Lung Cancer 2004 Oct
PMID:Docetaxel and Gemcitabine administered on days 1 and 8 for metastatic non-small cell lung carcinoma (NSCLC): a phase II multicenter trial. 1536 39

This trial was designed to determine the 1-year survival rate, efficacy, progression-free survival (PFS), and toxicity with gemcitabine in patients with stage IIIB (with pleural effusion) or stage IV non-small-cell lung cancer (NSCLC) with Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 2. Gemcitabine 1250 mg/m2 was administered intravenously on days 1 and 8 of each 21-day cycle. Treatment consisted of 6 cycles; patients who responded with complete response or partial response received < or = 2 additional cycles. Forty-two patients were enrolled at 31 community-based centers between March and November 2002. Most patients had stage IV disease (74%). The median age was 73 years (range, 58-84 years), and 19% had received prior palliative radiation therapy. Patients received a median of 3 cycles (range, 1-8 cycles). The median survival was 4.8 months (range, < 1 to 19.2 months), and the estimated 1-year survival was 20%. Median PFS was 2.5 months (range, < 1 to 19.2 months), and PFS at 1 year was 11.1%. Thirty-one patients died of disease progression, and 1 each died of myocardial infarction, brain herniation, pneumonia, and respiratory failure. Seven patients were not evaluable for response; 4 refused or received no treatment, treatment in 2 failed (myocardial infarction and pneumonia), and 1 was lost to follow-up. Among 35 evaluable patients, there were 5 partial responses (14%), 10 with stable disease (29%), and 20 with disease progression (57%). Drug-related grade > or = 3 toxicities included neutropenia (18%), anemia (8%), and dyspnea (2.6%). These results suggest that patients with NSCLC with an ECOG PS of 2 may benefit from single-agent chemotherapy gemcitabine. General toxicity, including myelotoxicity, was relatively low. Further studies comparing single-agent chemotherapy with combination chemotherapy for patients with a PS of 2 are warranted.
Clin Lung Cancer 2005 Jan
PMID:Results of a phase II trial of gemcitabine in patients with non-small-cell lung cancer and a performance status of 2. 1569 17

Gemcitabine is usually administered at a planned dose-intensity (DI) from 750 to 800 mg/m2/week. Preclinical data have suggested a possible dose-response relationship of gemcitabine. A multicenter phase II study was conducted to evaluate the activity in terms of no progression rate (complete responses+partial responses+stable diseases) of gemcitabine administered at an increased DI (1000 mg/m2/week) in elderly advanced non-small-cell lung cancer (NSCLC) patients. Secondary endpoints were to evaluate tolerability, progression free survival and overall survival. Elderly (age>or=70 years) chemo-naive advanced NSCLC patients, ECOG PS 0-2, were treated with intravenous gemcitabine 1500 mg/m2 intravenous (30 min infusion) on days 1 and 8 every 21 days for four courses. One hundred and twenty-two patients with a median age of 75 years (range 70-84) entered the study. The following grade 3 (NCI-CTC) haematological toxicities were reported (percent of patients): neutropenia 2.4%, thrombocytopenia 1.6%, anaemia 2.4%. No grades 3-4 non-haematological toxicities were observed. Among 111 evaluable patients 52 (46.8%) no progressions, 17 (15.3%) partial responses (WHO criteria), 35 (31.5%) stable diseases and 59 (53.2%) progressions were observed. Median time to progression was 3.2 months and median duration of survival was 5.4 months. The overall 1-year survival rate was 27%. Although increased dose-intensity of gemcitabine in elderly NSCLC patients is feasible without severe toxicities, this does not seem to be associated with an increased activity and efficacy in comparison to standard gemcitabine regimens with lower dose-intensities.
Lung Cancer 2005 Apr
PMID:Increased dose-intensity of gemcitabine in advanced non small cell lung cancer (NSCLC): a multicenter phase II study in elderly patients from the "polmone toscano group" (POLTO). 1577 79

The aim of this study was to evaluate the effect on tumour growth of gemcitabine delivered by aerosol in an orthotopic model of lung carcinoma. Large cell carcinoma (NCI-H460) cells were implanted intrabronchially in 24 male BALB/c nude mice on day (d) 0. Aerosols were delivered once a week from d1 to d29 using an endotracheal sprayer. Altogether, 16 animals received gemcitabine at 8 (n=8) and 12 mg.kg-1 (n=8), and eight received a vehicle aerosol. Animals were sacrificed on d36 for histological examination. All animals in the vehicle group developed a large infiltrating carcinoma. Comparatively, four of 13 (31%) animals treated with gemcitabine had no visible tumour and nine of 13 (69%) had a smaller carcinoma with a mean+/-sem largest tumour diameter of 2.05+/-0.7 versus 5+/-0.3 mm in the vehicle group. Gemcitabine was well tolerated at 8 mg.kg-1. At 12 mg.kg-1, three cases of fatal pulmonary oedema were observed, prompting a dose reduction to 8 mg.kg-1 in the remaining animals. A dose effect was observed, with more marked tumour growth inhibition in the animals treated at 12 mg.kg-1 on d1 and d8. In conclusion, in this study, an animal model of aerosolised chemotherapy in lung cancer was developed and demonstrated inhibition of orthotopic tumour growth by aerosol delivery of gemcitabine.
 ...
PMID:Aerosol delivery of chemotherapy in an orthotopic model of lung cancer. 1620 97

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 considered is to be a well-tolerated cytostatic drug with little known side effects. Cutaneous reactions are well known but still rarely reported. We report the case of a 75-year-old man with stage IV non-small-cell lung carcinoma treated with combination of gemcitabine 1000 mg/m2 and cisplatin 75 mg/m2 repeated every 28 days, who developed bilateral cutaneous bullous lesions of lower limbs following gemcitabine administration. Histopathologic examination did not show any toxidermy aspect and there was not any sign of immunoglobulin deposit in direct immunofluorescence test. Chemotherapy was stopped and lesions disappeared without any treatment. Even delayed with regard to gemcitabine administration, the causal relationship of gemcitabine treatment with skin reaction is possible according to the Naranjo probability scale. Pathologists should be aware of this kind of side effect in managing chemotherapy drugs and report any dermatologic reactions in order to identify the cause of toxicity and avoid a misdiagnosis.
 ...
PMID:Bullous dermatosis associated with gemcitabine therapy for non-small-cell lung carcinoma. 1643 73

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.
 ...
PMID:Development of gemcitabine in non-small cell lung cancer: the Italian contribution. 1680 61

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


<< Previous 1 2 3 4 5 6 Next >>