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)

Gemcitabine is one of the most active agents in the treatment of patients with advanced non-small-cell lung cancer (NSCLC). Recent evidence indicates that gemcitabine/cisplatin is among the most active doublets in advanced NSCLC, but the problem of what to give patients who cannot tolerate cisplatin still remains. The combination of gemcitabine/carboplatin is under investigation. Initially thought to be too myelosuppressive, recent schedule modifications have made this a more feasible doublet for NSCLC. Nonplatinum doublets consisting of gemcitabine with the taxanes or vinorelbine are also under investigation. This review covers the most current trials of gemcitabine-based doublets in advanced NSCLC.
Clin Lung Cancer 2002 Mar
PMID:Gemcitabine-based doublets for advanced non-small-cell lung cancer: beyond gemcitabine/cisplatin. 1472 Mar 49

Gemcitabine, docetaxel, and paclitaxel are among the most active agents available for the treatment of non small-cell lung cancer (NSCLC). Each has been shown to produce objective responses in approximately 20%-25% of previously untreated patients with advanced or metastatic NSCLC and to improve survival and quality of life when compared to best supportive care. In randomized clinical trials, these drugs have produced response rates and survival outcomes equal to older platinum-based regimens and, when combined with a platinum compound, have produced the best results achieved to date in this disease. Because of their effectiveness and moderate toxicity profiles, investigators have studied novel combinations of these new agents. Multiple phase II clinical trials have explored a variety of doses and schedules of gemcitabine combined with docetaxel or paclitaxel. Randomized clinical trials have shown that gemcitabine 1000-1100 mg/m2 administered on days 1 and 8 every 3 weeks combined with either docetaxel 100 mg/m2 on day 8 or paclitaxel 200 mg/m2 on day 1 can produce response rates and survival outcomes at least equivalent to the newer platinum-based taxane regimens. More recently, several investigators have explored weekly administration of either docetaxel or paclitaxel with gemcitabine. Preliminary results are encouraging and suggest that these novel gemcitabine/taxane regimens could provide an alternative to standard platinum-based regimens.
Clin Lung Cancer 2000 Dec
PMID:Gemcitabine and taxane combinations in non small-cell lung cancer. 1472 31

For stage III non small-cell lung cancer, there is a need for better systemic, as well as locoregional, control of the tumor. In an attempt to enhance this locoregional control, systemic chemotherapy has been given currently with radiation therapy. Gemcitabine, a novel deoxycytidine analogue, has been shown to be a potent radiosensitizer. This review focuses on the studies using gemcitabine concurrently with radiation therapy in the treatment of locally advanced non small-cell lung cancer.
Clin Lung Cancer 2000 Dec
PMID:Gemcitabine plus radiation therapy in the treatment of locally advanced non small-cell lung cancer. 1472 34

Two recent trials have suggested that docetaxel improves survival in the second-line treatment of non small-cell lung cancer (NSCLC) refractory to first-line platinum-based regimens. Given this, it is appropriate to continue to address the role of new agents in the second-line treatment of refractory NSCLC. Gemcitabine is a well-tolerated new agent that has been shown to have activity in NSCLC. Thirty-one previously treated patients with NSCLC were entered in this study. Eight patients had responsive disease (defined as response to first-line therapy lasting greater than or equal to 3 months) and 23 had refractory disease (defined as progressive disease on first-line therapy or progression less than 3 months from completing first-line therapy). Gemcitabine (1250 mg/m2) was infused over 30 minutes on days 1, 8, and 15 every 28 days. Quality of life (QOL) was assessed with each cycle using the Functional Assessment Cancer Therapy-Lung (FACT-L) questionnaire. Two patients (6.5%) had a partial response, and nine (29%) had disease stabilization. The most frequent grade 3/4 toxicity was myelosuppression, but this only occurred in 8% of doses delivered. Fifty-two percent of evaluable patients had stable or improved QOL over baseline, 10% had a decline in QOL, and the remainder completed only baseline questionnaires. Twenty-nine patients have died of progressive NSCLC; two patients remain alive. Overall, the 31 patients have a median survival of 5.1 months (95% confidence interval [CI]: 4.2-7.4 months) and 1-year survival rate of 16% (95% CI: 3%-29%). Gemcitabine was well tolerated in this patient population. An objective response rate of 6.5% was observed although a significant proportion of patients (29%) experienced stable disease, which may have impacted on their survival. QOL was improved or maintained in over half of the patients. Given these data, gemcitabine as a single agent is a therapeutic option for patients with refractory NSCLC.
Clin Lung Cancer 2000 Nov
PMID:Second-line gemcitabine in refractory stage IV non small-cell lung cancer: a phase II trial. 1473 24

Gemcitabine (G) and cisplatin (P) are active reference agents in patients with non-small-cell lung cancer (NSCLC). Ifosfamide (I) has also been approved for NSCLC treatment. This phase I trial aimed to determine the dose-limiting toxicity (DLT), maximum tolerated dose [maximum tolerated dosage (MTD)], and recommended dose (RD) of a GIP combination in patients with advanced/metastatic NSCLC. In this study, one cycle of chemotherapy combined the following: ifosfamide: 3 g/m2 fixed dose (24-hour intravenous infusion) combined with mesna, day 1; gemcitabine: starting dose 1,000 mg/m2/d, escalating by 250 mg/m2 increments, days 1 and 15; cisplatin: starting dose 80 mg/m2, subsequently 100 mg/m2, day 15; in cohorts of at least 3 patients. Cycles were repeated every 28 days and no hematopoietic growth factors were administered. DLT was evaluated after the first chemotherapy cycle. Thirty-three patients (30 men, 3 women) with stage III (14 patients)/IV (19 patients) NSCLC were treated at eight dose levels, receiving 109 cycles of chemotherapy. Neutropenia was the only DLT reported. Although the MTD was not reached at the highest tested dose level, the RD chosen corresponds to the full doses of the GP3000 doublet standard (G: 3,000 mg/m2; P: 100 mg/m2 per cycle) every 28 days. Nonhematologic toxicities were mainly grade I-II. Relative dose intensities of G, I, and P at the RD were 96%, 98%, and 96%, respectively. Sixteen of 33 patients with measurable/evaluable disease had an objective response including two complete responses. In conclusion, GIP chemotherapy is safe and appears to be active in patients with NSCLC. The RD is gemcitabine: 1,500 mg/m2 days 1 and 15; ifosfamide: 3 g/m2 day 1; cisplatin: 100 mg/m2 day 15. A confirmatory phase II study is currently under way, before a phase III trial of GIP versus GP.
 ...
PMID:Phase I study with dose escalation of gemcitabine and cisplatin in combination with ifosfamide (GIP) in patients with non-small-cell lung carcinoma. 1475 40

In the past decade unequivocal evidence regarding the benefit of platinum-based chemotherapy in the treatment of advanced non-small-cell lung cancer (NSCLC) has emerged. Several regimens consisting of either cisplatin or carboplatin combined with agents such as paclitaxel, docetaxel, gemcitabine, vinorelbine, or irinotecan have demonstrated superiority over older combinations or single-agent platinums. These regimens have roughly equivalent activity in terms of response and survival. The major differences have been in terms of toxicities and expense. Gemcitabine/carboplatin is a combination with clear activity in advanced disease and excellent tolerability. Unlike taxane-based therapy, there is minimal neuropathy and little alopecia. For registration purposes, gemcitabine was initially combined with cisplatin. Regimens combining gemcitabine with carboplatin reported a similar rate of myelotoxicity (primarily thrombocytopenia) as gemcitabine/cisplatin. The observation that a 21-day schedule in which carboplatin is administered on day 1 and gemcitabine on days 1 and 8 could substantially reduce this toxicity provided a preferred schedule for administration. The major factor limiting acceptance of this regimen was the absence of phase III data. This year a number of phase III trials were presented, which coupled with the results of large, multicenter phase II studies (including one from a US cooperative group), has now established gemcitabine/carboplatin as a standard regimen for the treatment of advanced NSCLC. Its excellent toxicity profile has also led several groups to utilize the regimen as a platform for combination with newer drugs.
Clin Lung Cancer 2003 Jan
PMID:Gemcitabine and carboplatin regimens in advanced non-small-cell lung cancer: focus on randomized phase III trials. 1487 Jul 15

Gemcitabine (2'-2'-difluorodeoxycytidine (dFdC)) is a deoxycytidine analogue that is effective against solid tumors, including lung cancer and ovarian cancer. dFdC requires the phosphorylation by deoxycytidine kinase (dCK) as a primary step in its activation. Deficiency of dCK is associated with resistance against this compound both in vitro in cancer cell lines and in clinical practice in acute myeloid leukemia and solid tumors. The human ovarian cancer cell line AG6000 is 100,000-fold resistant against dFdC compared to its parent cell line A2780. This cell line proved to be dCK deficient in enzyme activity assays and by Western blot analysis, but by RT-PCR, a normal and a truncated dCK mRNA was found. Sequencing revealed that exon 3 was deleted from the dCK cDNA, resulting in a 74-aa-long open-reading frame due to the generation of a premature stop codon. No gross genomic alteration was observed at the dCK locus, suggesting the involvement of post-transcription mechanisms. Transient transfection experiments indicated that the truncated dCK transcripts are not translated to protein. To study the functional role of the truncated dCK transcripts, both A2780 cells and AG6000 cells were stably transfected with human and rat dCK. The results indicated that over-expression of full-length dCK genes in AG6000 failed to completely reverse the sensitivity to dFdC or other drugs.
 ...
PMID:Detection of an alternatively spliced form of deoxycytidine kinase mRNA in the 2'-2'-difluorodeoxycytidine (gemcitabine)-resistant human ovarian cancer cell line AG6000. 1527 67

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

Several new antimetabolites, administered alone or in combination, are changing the therapeutic landscape for thoracic cancer. Two-drug combinations involving these newer drugs are becoming the standard of care for non-small-cell lung cancer (NSCLC), largely due to improvements in survival rates, time to disease progression, and response rates as well as an improved safety profile. Gemcitabine (Gemzar) has elicited considerable interest in this disease, as a combination partner in chemotherapeutic regimens. Another promising agent is pemetrexed (Alimta), a folate-based inhibitor of thymidylate synthase. In preclinical development, pemetrexed both alone and in combination with other cytotoxic agents has exhibited activity across a broad range of tumor models, including NSCLC and mesothelioma. In clinical trials of patients with NSCLC, pemetrexed has been an effective, well-tolerated agent that can be used as monotherapy or in combination with other agents at full dose. In clinical trials of patients with mesothelioma, the combination of pemetrexed and cisplatin demonstrated a significant improvement in survival, response, and patient quality-of-life parameters. The principle toxicities of pemetrexed can be minimized by folate and vitamin B12 supplements.
 ...
PMID:New investigative regimens and cytotoxic agents in thoracic cancers: gemcitabine and pemetrexed. 1533 53

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


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