Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242379 (lung cancer)
 71,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pemetrexed has recently been approved for use in combination with cisplatin as first-line chemotherapy for malignant pleural mesothelioma (MPM). Radiation therapy is frequently administered to the thoracic orifices and no data are available about the interactions between radiotherapy and pemetrexed. We report the first case of radiation recall dermatitis occurring after pemetrexed chemotherapy in a patient with MPM previously treated with radiation therapy to the thoracoscopy and drainage orifices. The patient received chemotherapy with pemetrexed and cisplatin 19 days after completion of chest wall radiation therapy delivering 21 gray in 3 days. Conventional premedication by folic acid and intramuscular administration of Vitamin B12 and prednisolone was correctly performed. Twelve days later, confluent erythematous and pruritus rash of the irradiated skin was observed. The toxicity grade of this lesion was evaluated at 2 according to the Acute Radiation Morbidity Scoring Criteria proposed by the Radiation Therapy Oncology Group. Pemetrexed challenge was performed without worsening of skin lesions. Three weeks later, skin cicatrisation was observed after a desquamative phase. Persistent hyperpigmentation was seen in the irradiated skin. Pemetrexed could also act as a radiosensitizing agent that should be used with care for several weeks after radiotherapy.
Lung Cancer 2005 Nov
PMID:Radiation recall dermatitis with pemetrexed. 1611 84

Platinum-based chemotherapy offers a modest survival advantage over best supportive care in chemotherapy-naive patients with a good performance status and advanced/metastatic non-small-cell lung cancer (NSCLC). Despite the survival benefit associated with first-line chemotherapy, the majority of patients will experience relapse or disease progression. In clinicalpractice, an increasing number of patients maintain a good performance status after first-line treatment and are eligible for further treatments. Docetaxel (Taxotere) at 75 mg/m2 given once every 3 weeks has been the standard of care for second-line chemotherapy since the year 2000. Pemetrexed (Alimta) is a novel multitargeted antifolate agent with single-agent activity in first- and second-line treatment of NSCLC. A large phase 111 study comparing docetaxel to pemetrexed in second-line therapy demonstrated that pemetrexed is equally active and less toxic than docetaxel. Based on these results, pemetrexed is a reasonable second-line chemotherapy option for patients with recurrent, advanced NSCLC. Progress made in the field of molecular biology has led to the identification of drugs active against specific cellular targets. Gefitinib (Iressa) and erlotinib (Tarceva) are both orally active tyrosine kinase inhibitors of the epidermal growth factor receptor. Phase II and III trials have demonstrated that these agents are active particularly in a subgroup of patients with specific biologic characteristics. Both drugs have been approved for the treatment of pretreated NSCLC. Other drugs, such as cetuximab (Erbitux) and bevacizumab (Avastin) have shown promising activity in NSCLC and are currently being tested in clinical trials.
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PMID:Perspectives on salvage therapy for non-small-cell lung cancer. 1613 Oct 43

Pemetrexed is a new cytotoxic agent that is a standard of care for the second-line treatment of non-small-cell lung cancer (NSCLC) and treatment of malignant pleural mesothelioma. It is currently in clinical development for the first-line treatment of NSCLC. In untreated advanced NSCLC, single-agent activity has been demonstrated in phase II trials. Pemetrexed has encouraging response rates and a favorable toxicity profile. Pemetrexed also has promising activity and acceptable toxicity when combined with platinum compounds or gemcitabine. Dietary supplementation with low-dose folic acid and vitamin B(12) significantly reduces the incidence and severity of toxicities without compromising the antitumor activity of pemetrexed. With its innovative mode of action, proven efficacy, favorable toxicity profile and convenient administration, pemetrexed represents a new therapeutic option for the treatment of advanced NSCLC.
Lung Cancer 2005 Oct
PMID:Pemetrexed: a new cytotoxic agent in the development for first-line non-small-cell lung cancer. 1629 26

The current prognosis for patients with extensive stage (ES) small-cell lung cancer (SCLC) remains poor, even though considerable improvements have been made in treatments for limited stage (LS) SCLC over the past several decades. Pemetrexed is an antimetabolite with an innovative mechanism of action. It demonstrates activity both as a single-agent and in combination regimens in patients with non-small-cell lung cancer (NSCLC) or malignant pleural mesothelioma. With an excellent antitumor activity, favorable tolerability profile, ease of administration and convenient schedule in NSCLC patients, pemetrexed is currently being investigated in a phase II trial for the first-line treatment of ES SCLC. Observations from this trial will help to define the future role of pemetrexed in SCLC.
Lung Cancer 2005 Oct
PMID:Seeking new options for the treatment of small-cell lung cancer. 1629 30

Pemetrexed (Alimta, Eli Lilly and Company, Indianapolis, IN) is a structurally novel anti-folate agent. The United States Food and Drug Administration has approved pemetrexed for the treatment of patients with malignant pleural mesothelioma and previously treated patients with locally advanced or metastatic non-small cell lung cancer. In the phase III trials that led to its approval, rash was reported in 17 and 22% of patients receiving pemetrexed alone or in combination with cisplatin. However, little has been published about the characteristics of this rash or about its mechanism. In an attempt to contribute to the growing body of knowledge about this new agent, we describe a case in which a patient developed a rash secondary to urticarial vasculitis associated with pemetrexed.
Lung Cancer 2006 Feb
PMID:Pemetrexed-associated urticarial vasculitis. 1636 Feb 37

Pemetrexed (ALIMTA) is a novel multitargeted antifolate that inhibits thymidylate synthase, dihydrofolate reductase, and glycinamide ribonucleotide formyltransferase. This agent is broadly active in a wide variety of solid tumors, including breast cancer, bladder cancer, mesothelioma, non-small-cell lung cancer, pancreatic cancer and ovarian cancer. Pemetrexed has also shown clinically relevant activity in combination with gemcitabine. This combination has been, and continues to be evaluated for the treatment of a number of malignancies, including non-small cell lung and ovarian cancer. A recently published randomized trial of different sequences has identified the sequence of pemetrexed on day 1 followed by gemcitabine on day 1 and gemcitabine on day 8, every 21 days as the most efficacious and least toxic sequence.
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PMID:Clinical studies of pemetrexed and gemcitabine combinations. 1680 59

Lung cancer is a leading cause of death world-wide and the long-term survival rate for lung cancer patients is one of the lowest for any cancer. New therapies are urgently needed. The present study was designed to evaluate an immunomodulatory oligonucleotide as a novel type of therapy for lung cancer. The in vivo effects of the immunomodulatory oligonucleotides were determined in four tumor models derived from human non-small cell lung cancer (NSCLC) cell lines (A549, H1299, H358, and H520), administered alone or in combination with conventional chemotherapeutic agents used to treat lung cancer. The in vitro effects of the immunomodulatory oligonucleotide on the growth, apoptosis, and proliferation of NSCLC cells were also determined. We also examined NSCLC cells for expression of Toll-like receptor 9 (TLR9), the receptor for the immunomodulatory oligonucleotide. We showed several important findings: (a) treatment with the immunomodulatory oligonucleotide led to potent antitumor effects, inhibiting tumor growth by at least 60% in all four in vivo models; (b) combination with the immunomodulatory oligonucleotide led to enhanced effects following treatment with gemcitabine or Alimta; (c) the immunomodulatory oligonucleotide increased apoptosis, decreased proliferation, and decreased survival in A549 cells in vitro; and (d) both TLR9 mRNA and protein were expressed in NSCLC cells. The immunomodulatory oligonucleotide has potent antitumor effects as monotherapy and in combination with conventional chemotherapeutic agents, and may act directly on NSCLC cells via TLR9. The present study provides a rationale for developing the immunomodulatory oligonucleotide for lung cancer therapy.
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PMID:Chemotherapy and chemosensitization of non-small cell lung cancer with a novel immunomodulatory oligonucleotide targeting Toll-like receptor 9. 1681 18

The combination of pemetrexed and cisplatin shows good clinical activity against mesothelioma and lung cancer. In order to study the potential cellular basis for this, and provide leads as to how to optimize the combination, we studied the schedule-dependent cytotoxic effects of pemetrexed and cisplatin against four human cancer cell lines in vitro. Tumor cells were incubated with pemetrexed and cisplatin for 24 h at various schedules. The combination effects after 5 days were analyzed by the isobologram method. Both simultaneous exposure to pemetrexed and cisplatin for 24 h and sequential exposure to cisplatin for 24 h followed by pemetrexed for 24 h produced antagonistic effects in human lung cancer A549, breast cancer MCF7, and ovarian cancer PA1 cells and additive effects in colon cancer WiDr cells. Pemetrexed for 24 h followed by cisplatin for 24 h produced synergistic effects in MCF7 cells, additive/synergistic effects in A549 and PA1 cells, and additive effects in WiDr cells. Cell cycle analysis of MCF7 and PA1 cells supported these findings. Our results suggest that the simultaneous clinical administration of pemetrexed and cisplatin may be suboptimal. The optimal schedule of pemetrexed in combination with cisplatin at the cellular level is the sequential administration of pemetrexed followed by cisplatin and this schedule is worthy of clinical investigations.
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PMID:Schedule-dependent interactions between pemetrexed and cisplatin in human carcinoma cell lines in vitro. 1689 69

Pemetrexed is a novel antimetabolite that targets multiple enzymes in the folate pathway, and has exhibited clear antitumor activities in the treatment of malignant pleural mesothelioma and non-small cell lung cancer. Although many adverse events of pemetrexed, such as bone marrow suppression, have been reported, edema of the eyelid has been previously reported in only one case (0.2%, n=519), according to the Pemetrexed Clinical Investigator's Brochure, April 2005 version. We experienced a patient who developed the valuable edema of the eyelid. We believe that medical oncologists should be aware of this rare adverse event, although the mechanism responsible for it is not yet known.
Lung Cancer 2006 Nov
PMID:Pemetrexed-induced edema of the eyelid. 1699 65

Aging society is coming now, the ratio of elderly patients among all lung cancer patients has currently been increasing. It is necessary for elderly patients who are under-represented in clinical trials to study their suitable regimen. Thus, phase II and III clinical trials have been performed specifically for elderly non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) patients all over the world. As for single agent chemotherapy, there is a strong rationale for docetaxel and vinorelbine in elderly patients with advanced NSCLC. Recently, there are phase I and II clinical trial for CPT-11 monotherapy, and gefitinib and TS-1 are reasonable options for elderly patients. Alimta is tolerable for elderly, and subset analysis is performed for the elderly with recurrent NSCLC. As platinum-based chemotherapy, there are several elderly subset analyses and JCOG 0207, which is a phase III trial now in progress comparing weekly cisplatin+weekly docetaxel and weekly docetaxel. In SCLC, there is no evidence of single agent chemotherapy but combination chemotherapy such as carboplatin+etoposide is recommended. A phase III study of carboplatin+etoposide versus amrubicin under way. These studies should aim to optimize several agents for elderly patients and prolong survival, palliative care.
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PMID:[Lung cancer]. 1735 26


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