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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Gemcitabine plus radiation therapy in the treatment of locally advanced non small-cell lung cancer. 1472 34

Palliative chemotherapy with gemcitabine, a common mode of treatment of pancreatic cancer, has little influence on patients' survival. We investigated the impact of anti-apoptotic Bcl-xL protein and its antagonist Bax on gemcitabine-induced apoptosis in human pancreatic carcinoma cells in vitro and in vivo. The level of Bcl-xL and Bax expression was determined in 3 established pancreatic cancer cell lines that differ in their sensitivity to gemcitabine-mediated apoptosis. Bcl-xL and Bax genes were transduced into Colo357 cells by retroviral infection. In addition, cells were transfected with c-FLIP to assess involvement of CD95 and caspase-8. The impact of Bax/Bcl-xL expression on gemcitabine-sensitivity in vivo was evaluated in orthotopic Colo357 tumors in SCID mice. The apoptotic index revealed a strong inverse correlation between Bcl-xL expression and gemcitabine-induced apoptosis in the pancreatic carcinoma cell lines tested. Caspase-8 and Bid were cleaved in Colo357 cells exposed to gemcitabine, and there was no correlation with either Bcl-xL or with Bax expression. In contrast, the lack of mitochondrial transmembrane potential transition, release of cytochrome-c and absence of caspase-9- and PARP-cleavage showed a strong correlation with Bcl-xL expression. Expression of c-FLIP significantly increased the resistance towards gemcitabine. Orthotopically growing Colo357-bcl-xl tumors in SCID mice were refractory to gemcitabine treatment, and in contrast to the in vitro data, Colo357-bax tumors exhibited a 12-fold greater tumor regression than Colo357-wild-type tumors in the control group. Gemcitabine-induced apoptosis involves the mitochondria-mediated signaling pathway. A functional restoration of this pathway appears to be essential to overcome the resistance mechanisms of pancreatic tumor cells and to improve the response to therapy as demonstrated by Bax overexpression in a clinically relevant tumor model.
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PMID:Resistance of pancreatic cancer to gemcitabine treatment is dependent on mitochondria-mediated apoptosis. 1475 Jan 67

Gemcitabine has been evaluated in combination with paclitaxel, docetaxel, anthracyclines, vinorelbine, and cisplatin as first-line treatment and after prior chemotherapy in patients with metastatic breast cancer. Results with gemcitabine/taxane combinations have been especially encouraging, with these combinations providing promising outcomes with regard both to tumor response and tolerability. The combination of gemcitabine and paclitaxel has garnered particular interest for further phase III evaluation on the basis of high response rates and durable responses in both treatment-naive and treatment-experienced patients, including anthracycline-pretreated patients.
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PMID:Gemcitabine combination chemotherapy in metastatic breast cancer: phase II experience. 1476

We have examined the application of (90)Y-DOTA-cPAM4, anti-MUC1 IgG, in combination with the front-line drug gemcitabine as a potential therapeutic for pancreatic cancer. Athymic nude mice bearing CaPan1 human pancreatic cancer xenografts were administered 2 mg of gemcitabine on days 0, 3, 6, 9 and 12 with concurrent (90)Y-DOTA-cPAM4 (100 microCi) provided on day 0. A second group of mice received a second cycle of treatment 5 weeks after the start of the first cycle. Control groups of mice included those that received either treatment arm alone, the combined modality treatment employing a nontargeting control antibody (hLL2, anti-B-cell lymphoma) and a final group that was left untreated. Gemcitabine administered as a single agent provided no antitumor effect. A single cycle of the combined (90)Y-DOTA-cPAM4 and gemcitabine treatment provided greater inhibition of tumor growth than was observed for any of the other treatment procedures. Tumor growth was delayed for a period of 7 weeks. Two cycles of gemcitabine with concomitant (90)Y-DOTA-cPAM4 yielded significant tumor regression and increased median survival to 21 weeks vs. 12 weeks for mice receiving a single cycle of therapy (p<0.024). Median tumor volume doubling-times were 18 weeks in mice treated with 2-cycles of therapy vs. 7 weeks in mice given only 1-cycle (p<0.001), and 3.5 weeks for the group that received 2-cycles of gemcitabine concomitant with equitoxic nontargeting (90)Y-DOTA-hLL2 (p<0.001). These data suggest that addition of (90)Y-DOTA-cPAM4 RAIT to a gemcitabine treatment regimen may provide enhanced antitumor efficacy for the treatment of pancreatic cancer.
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PMID:Combined 90Yttrium-DOTA-labeled PAM4 antibody radioimmunotherapy and gemcitabine radiosensitization for the treatment of a human pancreatic cancer xenograft. 1499 85

Despite advances in our understanding of the molecular and genetic basis of pancreatic cancer, the disease remains a clinical challenge. Gemcitabine, the standard chemotherapy for pancreatic cancer, offers modest improvement of tumor-related symptoms and marginal advantage of survival. New approaches, alone and in combination with gemcitabine, are being developed to combat this cancer. In this article we review the current status of investigations into several classes of agents: matrix metalloproteinase inhibitors; farnesyl transferase inhibitors; epidermal growth factor receptor inhibitors, including monoclonal antibodies and tyrosine kinase inhibitors; cyclooxygenase-2 inhibitors, and others. The scientific rationale, mechanism of action, and clinical trial data for these novel agents are discussed.
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PMID:Novel therapies for pancreatic adenocarcinoma. 1506 31

Of the new chemotherapeutic substances of the last decade, gemcitabine (Gemzar, Eli Lilly) is probably the most valuable for the treatment of early and advanced stage non-small cell lung cancer (NSCLC). When used as a single agent in both chemotherapeutically pretreated and chemotherapy-naive patients, gemcitabine shows an objective tumor regression rate of approximately 20%. Gemcitabine's unique mechanism of action and its lack of overlapping toxicity with other cytotoxic agents also define it as an ideal candidate for combination therapy. Early clinical development has included single-agent first- and second-line treatment, doublet combination regimens and incorporation into multimodality treatment strategies for operable and inoperable locally advanced nonmetastatic NSCLC. Gemcitabine/platinum-based combination chemotherapy has become the most attractive treatment standard for NSCLC patients in good clinical condition. The role of gemcitabine in the concurrent or sequential application of chemo- and radiotherapy for inoperable locally advanced NSCLC has also been addressed in several Phase I and II studies. Based on data available, gemcitabine can be safely administered in combination with radiotherapy. This review summarizes results from representative Phase I, II and III studies in order to underline gemcitabine's clinical importance for patients suffering from early and advanced NSCLC.
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PMID:Gemcitabine (Gemzar) in non-small cell lung cancer. 1516 34

Despite advances in our understanding of the molecular and genetic basis of pancreatic cancer, the disease remains a clinical challenge. Gemcitabine, the standard chemotherapy for pancreatic cancer, offers modest improvement of tumor-related symptoms and marginal advantage of survival. New approaches, alone and in combination with gemcitabine, are being developed to combat this cancer. In this article we review the current status of investigations into several classes of agents: matrix metalloproteinase inhibitors; farnesyl transferase inhibitors; epidermal growth factor receptor inhibitors, including monoclonal antibodies and tyrosine kinase inhibitors; cyclooxygenase-2 inhibitors, and others. The scientific rationale, mechanism of action, and clinical trial data for these novel agents are discussed.
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PMID:Novel therapies for pancreatic adenocarcinoma. 1519 89

Gemcitabine (GEM) is currently considered a standard drug for advanced pancreatic cancer and widely used for patients with this carcinoma. We report on 2 patients with unresectable pancreatic cancer who were able to survive for more than 2 years after GEM treatments. Case 1 was a 82-year-old woman with invasion to celiac artery and who was inoperable. During GEM administration, she had no symptoms and the tumor did not progress. However, because of the toxicities of heart failure, GEM administration was stopped after she took a total of 16,800 mg. After GEM administration was stopped, symptoms appeared and the tumor progressed. Case 2 was a 39-year-old man with obstructive jaundice with liver and lymph node metastases. He was treated with metallic stent in order to reduce cholestasis. During GEM administration, he had no symptoms and the tumor did not progress. As an adverse event, rash occurred after he took a total of 51,800 mg. GEM administration was then stopped. This patient sometimes developed cholestasis due to tumor ingrowths and sludge and was treated successful by endoscopy. GEM has shown to improve survival and show a clinically beneficial response in patients with advanced pancreatic cancer. However, toxic events can be expected to occur with long term GEM administration. We consider that management of complications such as obstructive jaundice is very important in the treatment of pancreatic cancer.
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PMID:[Two cases of advanced pancreatic cancer responding to gemcitabine with long survival of 2 years]. 1522 20

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).
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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.
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PMID:New investigative regimens and cytotoxic agents in thoracic cancers: gemcitabine and pemetrexed. 1533 53


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