Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033774 (pruritus)
 14,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The activity and toxicity profile of gefitinib in non-small cell lung cancer (NSCLC) patients aged 70 years or older has been only partially evaluated. The aim of this study was to evaluate the response rate and safety of gefitinib in elderly NSCLC patients. Elderly NSCLC patients pretreated with chemotherapy and with at least one measurable lesion received gefitinib at the daily dose of 250 mg until disease progression, unacceptable toxicity or refusal. From August 2001 to May 2003, 40 consecutive elderly patients have been enrolled onto the study in three Italian institutions. We observed one complete (2.5%) and one partial response (2.5%), 18 disease stabilisations (NC: 45%) lasting at least 2 months, including six patients (15%) who had disease stabilisation of 6 months or longer, for an overall disease control rate of 50% (95% CI: 34.5-65.5%). The median duration of response was 4.4 months (range 1.7-9.2). The side effects were generally mild and consisted of diarrhoea and skin toxicity. Grade 1-2 diarrhoea occurred in 23.6%, and one patient experienced grade 4 diarrhoea, requiring hospitalisation. Grade 1-2 skin toxicity, including rash, pruritus, dry skin, and acne, occurred in 20 patients (52.6%). Gefitinib is safe and well tolerated in elderly pretreated NSCLC patients. The disease-control rate achieved suggests that this drug could represent a valid option in the management of this unfavourable subgroup of patients.
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PMID:Efficacy and tolerability of gefitinib in pretreated elderly patients with advanced non-small-cell lung cancer (NSCLC). 1471 Feb 11

(1) Platinum-based chemotherapy is generally used to treat advanced-stage non small-cell lung cancer (stages III and IV), but has only a modest impact on survival. There is no reference treatment. (2) Gefitinib inhibits the tyrosine kinase activity of the receptor for EGF (epidermal growth factor), which is thought to be involved in tumour growth. It has a temporary licence in France and is used on a named-patient basis, but full marketing authorisation has already been granted in Japan, the United States, and elsewhere. (3) Two double-blind dose-finding studies compared two doses of oral gefitinib monotherapy (250 mg/day and 500 mg/day) in patients in whom at least two lines of chemotherapy had failed. The results were favourable, with a median survival of 6 months and a symptomatic improvement in some patients, but they are undermined by the absence of a placebo group and by major protocol violations. (4) Two double-blind trials, each in more than 1000 patients, showed that gefitinib does not increase the efficacy of first-line platinum combinations. (5) About 15% of patients receiving gefitinib monotherapy in clinical trials stopped taking the treatment because of adverse events. The most frequent were gastrointestinal (diarrhea, nausea, vomiting) and cutaneous (rash, acne, dry skin, pruritus). (6) Interstitial pneumonitis occurred in about 1% of patients, and was fatal in about one-third of cases. (7) Gefitinib is metabolised by the cytochrome P450 isoenzyme CYP3A4, so carries a potentially high risk of interactions. (8) In practice, more thorough assessment of gefitinib is needed to determine whether this new drug is beneficial for patients with non small-cell lung cancer. Marketing authorisation is not currently justified.
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PMID:Gefitinib: new preparation. Non small-cell lung cancer: stricter assessment needed. 1549 96

Cytotoxic chemotherapy treatment options for patients with non-small-cell lung cancer (NSCLC) have limited efficacy and are often associated with significant toxicity. Therefore, there is an unmet need for novel drugs that are not only effective in treating this disease but are also well tolerated. Gefitinib is an orally active epidermal growth factor receptor tyrosine kinase inhibitor that blocks the signal transduction pathways implicated in cancer cell growth and survival. It has recently been approved for the treatment of advanced/refractory NSCLC. This review presents the tolerability data from phase I and II gefitinib monotherapy trials, along with data from the worldwide 'Expanded Access Programme' and post-marketing use of gefitinib. Gefitinib was found to be generally well tolerated at the approved dosage of 250 mg/day; the most commonly reported adverse drug reactions (ADRs) were mild to moderate skin rash and diarrhoea, which were manageable and non-cumulative. Other ADRs observed with the use of gefitinib included: dry skin, pruritus, acne, nausea, vomiting, anorexia, asthenia and asymptomatic elevations in liver transaminase levels. Well recognised adverse effects seen with cytotoxic chemotherapy (such as bone marrow depression, neurotoxicity and nephrotoxicity) were not observed. Although the frequency and severity of ADRs increased with the dosage across the range studied (50-1000 mg/day), few patients required dosage reductions or the withdrawal of treatment, and those who did usually received gefitinib >or=600 mg/day.Thus, the available data indicate that gefitinib is well tolerated in patients with a range of solid tumours, including locally advanced or metastatic NSCLC.
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PMID:Overview of the tolerability of gefitinib (IRESSA) monotherapy : clinical experience in non-small-cell lung cancer. 1555 44

Gefitinib is a tyrosine kinase inhibitor that targets and inhibits epidermal growth factor receptors. It was initially used to treat non-small cell lung cancer but has increasingly been used for other solid tumors such as those in the breast, colorectal sites, and head and neck, as in our patient. Vitiligo is an autoimmune disorder that results in the destruction of melanocytes and subsequent skin depigmentation and hypopigmentation. Previously described mucocutanous side effects of gefitinib at 250-500 mg/day include alopecia, asteatotic dermatitis, desquamation, hyperpigmentation, papulopustular acneiform eruption, pruritus, seborrheic dermatitis, and skin fragility. A 54-year-old man with metastatic squamous cell carcinoma to the parotid gland developed vitiligo within 1 month of starting gefitinib therapy. We retrospectively reviewed the medical literature using PubMed, searching: (1) gefitinib side effects, (2) drugs and (3) vitiligo. The patient with gefitinib-induced vitiligo continued to receive treatment with the drug during which time areas of skin hypopigmentation persisted and progressed. Etiology of drug-induced vitiligo includes alopecia areata therapies, anticonvulsants, antimalarials, antineoplastics, anti-Parkinson medications, and other miscellaneous drugs. No other individuals have been described with gefitinib-induced vitiligo. Albeit rare, gefitinib may be associated with the development of vitiligo.
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PMID:Gefitinib-associated vitiligo: report in a man with parotid squamous cell carcinoma and review of drug-induced hypopigmentation. 2413 63

Lung cancer is currently one of the leading causes of the cancer-related deaths in the world. Erlotinib and Gefitinib are inhibitors of human epidermal growth factor receptor-1 and the epidermal growth factor receptor tyrosine kinase. The most common adverse events for erlotinib and gefitinib were mild to moderate skin toxicity (rash, itching, and dry skin), gastrointestinal reactions (diarrhea and nausea), and fatigue. Erlotinib induced gastrointestinal bleeding is rare, and dose-related. We are reporting a lung cancer patient who received erlotinib and gefitinib. The patient was sensitive to drug and tumor growth was inhibited. However, adverse reactions appeared as drug treatment continued, including gastrointestinal bleeding.
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PMID:Erlotinib and gefitinib treatments of the lung cancer in an elderly patient result in gastrointestinal bleeding. 2435 36

Icotinib is the first oral epidermal growth factor receptor (EGFR) tyrosine kinase receptor inhibitor, which has been proven to exert significant inhibitory effects on non-small cell lung cancer in vitro. Clinical evidence has showed that the efficacy of Icotinib on retreating advanced non-small cell lung cancer is comparable to Gefitinib. However, different phenotypes of EGFR can affect the therapeutic outcomes of EGFR tyrosine kinase receptor inhibitor. Therefore, our study focused on efficacy and safety of Icotinib in patients with advanced non-small cell lung cancer of different EGPR phenotypes. Clinical data of patients with advanced non-small cell lung cancer who received Icotinib treatment from August, 2011 to May, 2013 were retrospectively analyzed. Kaplan-Meier analysis was used for survival analysis and comparison. 18 wild-type EGFR and 51 mutant type were found in a total of 69 patients. Objective response rate of patients with mutant type EGFR was 54.9 % and disease control rate was 86.3 %. Objective response rate of wild-type patients was 11.1 % (P = 0.0013 vs mutant type), disease control rate was 50.0 % (P = 0.0017). Median progression-free survival (PFS) of mutant type and wild-type patients were 9.7 and 2.6 months, respectively (P < 0.001). Median PFS of exon 19 mutated mutant patients was 11.3 months, mean PFS of exon 21 L858R mutated mutant patients was 8.7 months (P = 0.3145). Median overall survival (OS) of EGFR mutated patients had not reached. OS time of 13 wild-type patients was 12.9 months (P < 0.001). The common adverse reactions of Icotinib included rash, diarrhea, itching skin with occurrence rates of 24.6 % (17/69), 13.0 % (9/69), and 11.6 % (8/69), respectively. Most adverse reactions were grade I-II. Icotinib has great efficacy in EGFR mutated patients, making it an optimal regimen to treat EGFR mutated patients. Furthermore, most of adverse reactions associated with Icotinib treatment were tolerable.
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PMID:Effects of icotinib on advanced non-small cell lung cancer with different EGFR phenotypes. 2477 8

Background: This meta-analysis evaluated the efficacy and toxicity of gefitinib with other commonly used drugs in different treatment settings and epidermal growth factor receptor (EGFR) mutation status. Methods: Nineteen randomize clinical trials (RCTs) of 6,554 patients with NSCLC were pooled in this meta-analysis by random-effects or fixed-effects model, whichever is proper. Results: In first-line therapy, gefitinib showed higher odds than chemotherapy (OR = 2.19, 95% CI: 1.20-4.01), but less than other targeted therapies (OR = 0.58, 95% CI: 0.38-0.88). As non-first-line therapy, the overall survival (OS) and progression-free survival (PFS) were similar between gefitinib and controls (HR = 1.00, 95% CI: 0.93-1.08; HR = 0.91, 95% CI: 0.72-1.15), respectively. With the regard to toxicity, the incidences of dry skin, rash and pruritus were higher in gefitinib compared with controls, while gefitinib significantly reduced the incidence of hematologic toxicity. Conclusion: Gefitinib might be more efficient than chemotherapy, but less efficient than other targeted therapies in ORR, especially in EGFR mutation-positive patients. Gefitinib can decrease the odds of hematologic toxicity compared to controls. Future studies, especially those with EGFR mutation-positive patients, will be needed to confirm our findings.
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PMID:The Efficacy and Toxicity of Gefitinib in Treating Non-small Cell Lung Cancer: A Meta-analysis of 19 Randomized Clinical Trials. 2972 Oct 56

Gefitinib is a multi-target tyrosine kinase inhibitor used for the treatment of non-small cell lung cancer. Papulo-pustular and/or paronychia, abnormalities in hair growth, itching, and dryness due to epidermal growth factor inhibitors - i.e., PRIDE Complex - are a common effect of tyrosine kinase inhibitors. We report a case of hair and eyebrow hyperpigmentation after 7 months of treatment with gefitinib. In the literature, we found no data regarding rapid pigmentation of hair due to treatment with any multi-target tyrosine kinase inhibitors. To our knowledge, this is the first case reporting both hair and eyebrow hyperpigmentation. We hypothesize the role of different mechanisms linked to rapid hair hyperpigmentation.
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PMID:The Dark Side of Gefitinib: Reflectance Confocal Microscopy Applied to Hair Hyperpigmentation. 3202 62

Gefitinib (Iressa), is a selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), used in the targeted treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC). Skin toxicity is the major adverse effect observed in patients treated with EGFR-targeted TKIs such as gefitinib and erlotinib. To date, a corresponding skin animal model has not been established to address the mechanisms of these effects. Therefore, we analyzed the skin rash phenotype and its pathological features in Brown Norway (BN) rats treated with gefitinib 2.5 mg, 5.0 mg, or 10 mg/100 g/day for 4 weeks. We found that treatment with gefitinib led to weight loss, rash, itching, and hair loss in a dose-dependent manner. We also investigated the skin pathology and found that the animal model showed thickening of the epidermis, loss of moisture, and apoptosis of keratinocytes. Immunohistochemistry, flow cytometry, and analysis of monocytes and leukocytes in the blood revealed increased macrophage infiltration was associated with the cutaneous toxicities induced by gefitinib in the BN rats. Finally, we found that gefitinib-induced cutaneous toxicity is significantly associated with three inflammatory cytokines known to be secreted by activated macrophages, TREM-1, CINC-2, and CINC-3.
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PMID:Gefitinib-Induced Cutaneous Toxicities in Brown Norway Rats Are Associated with Macrophage Infiltration. 3302 29