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Query: UMLS:C0242379 (lung cancer)
 71,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Patients with locally advanced or metastatic non-small-cell lung cancer (stage III and IV) who are not candidates for surgery and exhibit good performance status are typically treated with concurrent radiation and platinum-based chemotherapy for disease palliation. Platinum-based chemotherapies, used alone or with radiation therapy, offer a small but significant survival benefit compared with supportive care. The incorporation of first-line agents such as gemcitabine (Gemzar), vinorelbine (Navelbine), and paclitaxel, as well as second-line agents such as docetaxel (Taxotere), in doublet and triplet combinations has had a further significant therapeutic impact. Randomized trials have shown that cisplatin-based therapy in combination with new agents results in improved 1- and 2-year survival rates in patients with adequate performance status. The 1-year survival benefit has significantly improved, with greater symptom relief and improved quality of life in these patients. Thus, delaying disease progression with combination chemotherapy appears both beneficial and cost-effective in patients with advanced non-small-cell lung cancer. Newer approaches--including targeting critical signaling pathways, such as tyrosine kinase receptors, angiogenesis, and downstream signal transduction mechanisms--may provide novel agents with an improved toxicity profile and the potential for better disease management.
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PMID:State-of-the-art treatment for advanced non-small-cell lung cancer. 1472 2

New agents with improved systemic activity are needed for the treatment of lung cancer. Irinotecan (Camptosar) is a promising agent in advanced non-small-cell (NSCLC) and small-cell lung cancer (SCLC). In a Japanese phase III trial of advanced NSCLC, irinotecan or irinotecan/cisplatin demonstrated a significant survival advantage compared to the standard of vindesine/cisplatin. Similar North American phase III trials focusing on irinotecan's role in NSCLC are under way. Ongoing trials have also been launched to corroborate the significant survival advantage reported by a Japanese phase III trial for irinotecan/cisplatin vs standard etoposide/cisplatin in extensive SCLC. Current and planned trials in NSCLC with irinotecan in combination with gemcitabine (Gemzar), the taxanes, and other new agents, and thoracic radiotherapy should also provide useful clinical data. Moreover, trials in SCLC are investigating the rationale of combining irinotecan with a platinum agent as a component of chemoradiotherapy regimens. Promising data from these and other studies will further elucidate a role for irinotecan in the management of lung cancer.
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PMID:Irinotecan in advanced lung cancer: focus on North American trials. 1525 64

Locally advanced non-small-cell lung cancer represents 30% to 40% of all pulmonary malignancies. Most patients will die of the disease after aggressive contemporary treatments. Therefore, significant improvement in therapeutic methods must be implemented to improve overall survival rates. The arrival of a new generation of chemotherapeutic agents--including the taxanes, gemcitabine (Gemzar), and topoisomerase inhibitors such as irinotecan (Camptosar) and topotecan (Hycamtin)--offers the hope of significant advances in the treatment of lung cancer. Irinotecan and topotecan are camptothecin derivatives that inhibit topoisomerase I enzyme. It is believed that topoisomerase I inhibitors stabilize a DNA/topoisomerase I complex and interact with replication machinery to cause cell death. A significant amount of data demonstrates that these topoisomerase I inhibitors also act as radiosensitizers. With the increasing data that support concurrent chemoradiation treatment for malignancies, including lung cancer and head and neck cancers, there is an impetus to pursue the additional drugs that may potentially improve local control and survival. Irinotecan is undergoing early clinical trials in the combined-modality setting in several different disease sites. This paper will review the data on the role of camptothecin derivatives as a radiosensitizer and as a component of combined-modality therapy for lung cancer. It is hoped that newer treatment strategies, like the combination of radiation and topoisomerase I inhibitors, will have a significant impact on cure rates in the future.
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PMID:Topoisomerase I inhibitors in the combined-modality therapy of lung cancer. 1525 65

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

Standard first-line chemotherapy for the majority of patients with advanced non-small-cell lung cancer (NSCLC) consists of platinum-based combination regimens including one of the newer-generation agents, such as gemcitabine (Gemzar), a taxane, vinorelbine (Navelbine), or irinotecan (Camptosar). Several effective regimens are available, the choice of which will depend on treatment goals, individual patient or disease factors, as well as physician preferences. This paper surveys randomized trials of many of the newer-generation chemotherapy combinations in patients with advanced NSCLC to examine several issues, such as which new-generation regimen to use, whether a platinum agent is needed, the optimal number of drugs in the combination, and treatment duration.
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PMID:Current paradigms in first-line treatment of non-small-cell lung cancer. 1533 54

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

The treatment of advanced non-small-cell lung cancer (NSCLC) has evolved rapidly over the past few years. Systemic chemotherapy is associated with both quality of life and modest survival benefit for patients with advanced NSCLC. Platinum-based doublet combinations are the "standard of care." The US Food and Drug Administration (FDA) has approved gemcitabine (Gemzar), a pyrimidine analog, to be used in combination with cisplatin for the treatment of advanced NSCLC in the first-line setting. Randomized clinical trials have established comparable efficacy with improved therapeutic index for the carboplatin/gemcitabine regimen when compared with cisplatin/gemcitabine and other platinum doublets. Nonhematologic toxicities occur at a lower frequency with carboplatin/gemcitabine combinations compared with other "standard" platinum-based doublets, whereas dose-limiting thrombocytopenia, the most common toxicity, rarely requires therapeutic intervention. Both the 3- and 4-week schedules of carboplatin/gemcitabine result in similar efficacy and toxicity profiles, but the 3-week regimen is preferred. The combination of carboplatin and gemcitabine is an effective regimen with an acceptable toxicity profile for the treatment of advanced NSCLC. This regimen can also be used as a foundation for the development of innovative combinations with molecularly targeted agents.
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PMID:Carboplatin/gemcitabine combination in advanced NSCLC. 1533 55

Standard first-line chemotherapy regimens in advanced non-small-cell lung cancer (NSCLC) include carboplatin (Paraplatin)/paclitaxel, cisplatin/docetaxel (Taxotere), cisplatin/gemcitabine (Gemzar), and cisplatin/vinorelbine (Navelbine). An informal meta-analysis of 13 randomized trials of these regimens in NSCLC indicates no marked differences in terms of response rates or survival, but toxicity advantages with cisplatin/gemcitabine and cisplatin/vinorelbine regimens. An informal meta-analysis to assess the feasibility of substituting carboplatin for cisplatin in combination with gemcitabine or docetaxel shows no marked differences in efficacy between cisplatin- and carboplatin-containing regimens, although a slight trend favoring carboplatin/gemcitabine treatment may be observed; comparison of toxicity profiles among carboplatin-based regimens suggests advantages for carboplatin/gemcitabine treatment. A formal meta-analysis of 13 trials comparing gemcitabine/platinum combinations with other platinum-based regimens in NSCLC indicates significant improvements in progression-free survival and overall survival with gemcitabine/platinum treatment. On balance, available data suggest that carboplatin/gemcitabine may be the first-line option with the best therapeutic index.
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PMID:Gemcitabine-containing regimens vs others in first-line treatment of NSCLC. 1533 56

Research to identify the optimal drugs for use in chemoradiotherapy has led to the development of the potent radiosensitizing agent gemcitabine (Gemzar), which has exhibited excellent activity in non-small-cell cancer. When used in sequential chemoradiotherapy regimens, gemcitabine has been associated with response rates of 57% to 68%. A full dose of gemcitabine (1,000 mg/m2) can be safely used as induction therapy, and there is no definitive indication of enhancement of radiotoxicity. In addition, results from phase I/II trials support the efficacy of concurrent gemcitabine/radiation therapy in improving overall response rates and overall survival. Rates of 68%, 37%, and 28%, respectively, for 1-, 2-, and 3-year survival have been reported for gemcitabine/cisplatin chemotherapy administered concurrently with radiotherapy. Although the optimal dose has yet to be determined, a weekly dose of 300 mg/m2 appears to be effective with an acceptable toxicity level. Additional clinical trials are warranted to assess the long-term efficacy and safety of gemcitabine in combination with other chemotherapeutic agents and radiation therapy for treatment of non-small-cell lung cancer.
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PMID:Chemoradiation in NSCLC: focus on the role of gemcitabine. 1533 58

The use of chemotherapy in the treatment of early and advanced non-small-cell lung cancer (NSCLC) has increased during the past decade. One of the main reasons for the increased acceptance of chemotherapy is the development of several new cytotoxic agents with a unique mechanism(s) of action and high single-agent activity, combined with a favorable toxicity profile. Pemetrexed (Alimta) is a novel antifolate that inhibits several enzymes involved in DNA synthesis (thymidylate synthase [TS], dihydrofolate reductase [DHFR], and glycinamide ribonucleotideformyltransferase [GARFT]). Pemetrexed's toxicity is markedly reduced by folic acid and vitamin B12 supplementation. The compound has been studied extensively in various tumor types, including NSCLC. In NSCLC, pemetrexed at 500 mg/m2, every 3 weeks, given i.v. over 10 minutes, has shown promising activity, and can safely be administrated with vitamin supplementation. After registration, single-agent pemetrexed will certainly add to the chemotherapeutic options available for pretreated patients and will most likely change significantly chemotherapy prescriptions in second-line chemotherapy. In first-line chemotherapy, the role of platinum-based and -free combination doublet chemotherapy with pemetrexed still needs to be defined. Phase II data indicate high efficacy combined with favorable toxicity for pemetrexed in combination with cisplatin, carboplatin (Paraplatin), oxaliplatin (Eloxatin), gemcitabine (Gemzar), and vinorelbine (Navelbine). This review summarizes the clinical experience obtained thus far during the early clinical development of pemetrexed in NSCLC.
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PMID:Pemetrexed: its promise in treating non-small-cell lung cancer. 1533 59


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