Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.2 (alanine aminotransferase)
 26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

EKB-569 is a potent, low molecular weight, selective, and irreversible inhibitor of epidermal growth factor receptor (EGFR) that is being developed as an anticancer agent. A phase 1, dose-escalation study was conducted in Japanese patients. EKB-569 was administered orally, once daily, in 28-day cycles, to patients with advanced-stage malignancies known to overexpress EGFR. Two patients with advanced non-small cell lung cancer with EGFR mutations and acquired gefitinib resistance from the phase 1 study are described in detail. Case #1 is a 63-year-old man with smoking history. He received treatment from 4 March 2004. Because he had no severe adverse events, a total of 10 courses of therapy were completed through December 16. Grade 2 skin rash and ALT elevation, and grade 1 diarrhea and nail changes developed. A chest CT scan on 4 August 2003 revealed multiple pulmonary metastases that had decreased in size. Case #2 is a 49-year-old woman with no smoking history. She received therapy from 9 February 2004. She received a total of five courses of the therapy until 22 June 2004. Grade 3 nausea and vomiting and grade 1 diarrhea and dry skin developed. A chest CT scan on March 3 revealed multiple pulmonary metastases that had decreased in size. A brain MRI on March 4 showed that multiple brain metastases also had decreased in size. Based on RECIST criteria, they had stable disease but radiographic tumor regression was observed.
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PMID:EKB-569, a new irreversible epidermal growth factor receptor tyrosine kinase inhibitor, with clinical activity in patients with non-small cell lung cancer with acquired resistance to gefitinib. 1636 94

To assess the long-term safety of a topical solution of diclofenac sodium in a vehicle containing dimethyl sulfoxide (TDiclo), subjects with radiologically confirmed, symptomatic osteoarthritis of the knee(s) applied the clinical dose of TDiclo (40 drops, four times daily) to each painful knee for up to 52 weeks. Safety assessment included adverse events, skin irritation scores of the treated knee(s), ocular examinations, and routine laboratory tests. There were 793 subjects (mean age, 62.5 years) who applied TDiclo to one or both (72%) knees for an average of 204 days, including 463 subjects for 6 months and 144 for 1 year. The most frequent adverse events were at the application site with no increase in incidence with prolonged exposure: dry skin (25.3%), contact dermatitis without vesicles (13.0%) or with vesicles (9.5%). Skin irritation score was 0 (normal) in 61.0% of subjects, 0.5 (dryness or flaking) in 23.9%, 1 or 2 (erythema without or with induration) in 6.9%, and 3 or 4 (erythema with induration and vesicles/bullae) in 8.2%. Subject dropouts included 114 (14.4%) with an application site skin adverse event. Individual subject laboratory test shift to abnormal occurred for hemoglobin (3.2%), aspartate aminotransferase (6.4%), alanine aminotransferase (7.3%), and creatinine (4.2%), but few shifts (less than 0.3% per variable) were clinically significant. No increased risk of cardiovascular or cataract events was noted. This long-term study of TDiclo revealed a safety profile comparable to that shown in multiple, shorter, well-controlled, double-blind trials with the predominant adverse effect noted being an application site reaction.
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PMID:A long-term, open-label study to confirm the safety of topical diclofenac solution containing dimethyl sulfoxide in the treatment of the osteoarthritic knee. 2021 3