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

Small cell lung cancer is a chemosensitive disease; however, patients with extensive-stage disease or adverse prognostic factors are rarely cured. Gemcitabine (Gemzar; Eli Lilly and Company, Indianapolis, IN), a new agent with good tolerability, interacts synergistically with platinum agents. Carboplatin is as effective as cisplatin, but is less toxic. The London Lung Cancer Group is conducting a multicenter, open-label, randomized, phase III trial in patients with histologically or cytologically proven small cell lung cancer and extensive-stage, limited-stage but locally-advanced, or limited-stage disease with poor prognostic factors. Chemotherapy consists of 21-day cycles of gemcitabine 1,200 mg/m(2) intravenous (IV) on days 1 and 8, plus carboplatin area under the curve of 5 IV on day 1, or cisplatin 60 mg/m(2) IV on day 1 plus etoposide 120 mg/m(2) IV on day 1 and 100 mg orally on days 2 and 3. Thirty-nine patients have been randomized to gemcitabine/carboplatin and 38 to cisplatin/etoposide (23 and 22 completed treatment, with 96 and 84 cycles, respectively). Preliminary toxicity data indicate hematologic toxicity in 25% of cycles for gemcitabine/carboplatin and 16% for cisplatin/etoposide, although cisplatin/etoposide-treated patients experienced significant alopecia, nephrotoxicity, nausea and vomiting, and neutropenia. This London Lung Cancer Group trial of gemcitabine/carboplatin may define an active, safe, and acceptable treatment for patients with extensive-stage and poor-prognosis small cell lung cancer. Semin Oncol 28 (suppl 10):15-18.
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PMID:Gemcitabine/carboplatin versus cisplatin/etoposide for patients with poor-prognosis small cell lung cancer: a phase III randomized trial with quality-of-life evaluation. 1151 29

The inherent or induced resistance of tumors to cytostatic agents is a major clinical problem. In this review, we summarize the pre-clinical mechanisms of acquired and inherent resistance to the fluorinated deoxycytidine analog gemcitabine (2',2'-difluorodeoxycytidine, dFdC, Gemzar((R))), which has proven activity in non-small cell lung carcinoma, pancreatic and bladder cancer. Extensive research has been performed to elucidate the complex mechanism of action of this relatively new drug. Gemcitabine requires phosphorylation to mono-, di- and triphosphates to be active. Similar to the structurally and functionally related deoxycytidine analog ara-C, the first, crucial step in phosphorylation is catalyzed by deoxycytidine kinase (dCK). However, in contrast to ara-C, gemcitabine has multiple intracellular targets; up- or down-regulation of these targets may confer resistance to this drug. Resistance is associated with altered activities of enzymes involved in the metabolism of the drug, of target enzymes, and of enzymes involved in programmed cell death. However, the only strong correlations with gemcitabine sensitivity are dCK activity and dFdCTP pools, with a potential important role for ribonucleotide reductase.
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PMID:Determinants of resistance to 2',2'-difluorodeoxycytidine (gemcitabine). 1212 61

Several chemotherapeutic regimens have emerged in the past 5 years with the capability to improve survival and quality of life of patients with advanced non-small cell lung cancer (NSCLC). Among these treatments, the regimen of gemcitabine (Gemzar) and carboplatin (Paraplatin) has gained increasing acceptance. The combination of these two drugs was initially hampered by unacceptable platelet toxicity. However, the use of a 21-day schedule with the administration of gemcitabine on days 1 and 15 or the use of a 28-day schedule with the omission of day-15 gemcitabine has clearly been well tolerated and active. Unlike taxane based regimens, there is no need for steroid premedication, and neurotoxicity and alopecia are absent. This regimen is well tolerated and easily administered on an outpatient basis. It therefore represents an excellent "platform regimen" for the addition of new agents, particularly those associated with minimal myelotoxicity. Three-drug regimens consisting of gemcitabine/carboplatin and a taxane have been evaluated both with concurrent and sequential administration of the drugs. Trials are under way or planned for the addition of novel agents such as C225, UCN-01, PKC-alpha antisense, bexarotene, COX-2 inhibitors and other agents.
Lung Cancer 2002 Nov
PMID:Past, present, and future of gemcitabine and carboplatin regimens in advanced non-small cell lung cancer. 1243 28

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

The epidermal growth factor receptor (EGFR) is often overexpressed or dysregulated in solid tumors. Targeting the EGFR-mediated signaling pathway has become routine practice in the treatment of lung, pancreatic, head and neck, and colon carcinomas. Available agents with selected activity towards the EGFR include low molecular weight tyrosine kinase inhibitors, e.g., erlotinib (Tarceva, Genentech BioOncology/ OSI Pharmaceuticals/ F. Hoffmann-La Roche) and monoclonal antibodies, such as cetuximab (Erbitux, Bristol-Myers Squibb/ ImClone Systems/ Merck) and panitumumab (Vectibix, Amgen). Their use is anticipated to increase for treating other solid tumors that are dependent on this pathway for growth and proliferation. Health Canada and the US FDA have approved erlotinib for the treatment of advanced non-small cell lung carcinoma (NSCLC). It has also been approved in the US for use against pancreatic cancer in combination with gemcitabine (Gemzar, Eli Lilly). Cetuximab and most recently panitumumab (Vectibix, Amgen/ Abgenix) were approved by the US FDA for metastatic colorectal carcinoma. Cetuximab is also approved in the US for head and neck squamous cell carcinoma. The safety profile for this class of drugs is unique, with virtually no hematological toxicity, but frequent cutaneous and gastrointestinal side-effects. Although there is a dearth of randomized trials addressing treatment of the dermatological side-effects, some basic principles of management have been agreed upon and can likely improve patient compliance and decrease inappropriate dose reduction, which may negatively influence the antitumor effect.
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PMID:Cutaneous reactions to anticancer agents targeting the epidermal growth factor receptor: a dermatology-oncology perspective. 1776 2

Gemcitabine (Gemzar) is a nucleoside analogue used as a cytotoxic agent for the treatment of various carcinomas: pancreatic cancer, bladder cancer, breast cancer, and non-small-cell-lung cancer. Carboplatin, a DNA alkylating agent, is used alongside with gemcitabine in a regimen known as GemCarbo chemotherapy to treat several different types of cancer, most commonly lung cancer. We report an unusual case of hand-foot hyperpigmentation after the use of GemCarbo therapy on a man with stage IV non-small cell lung carcinoma. Physical examination revealed hyperpigmented lesions that were approximately 1-2 mm in diameter, of brown/purple discoloration localized to the palmar surface of his hands and the dorsum of his feet. A rapid plasma reagin blood test, used for the screening of syphilis was nonreactive. Discontinuation of both agents resulted in the dramatic disappearance of the lesions over the course of 2 weeks. In this report, we describe, to our knowledge, the first case of hand-foot hyperpigmentation that has been reported with the use of either of these 2 agents.
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PMID:Hand-foot hyperpigmentation skin lesions associated with combination gemcitabine-carboplatin (GemCarbo) therapy. 2046 Sep 84