Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0206061 (interstitial pneumonia)
 6,105 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gefitinib is an oral selective inhibitor of the epidermal growth factor receptor tyrosine kinase that is an effective treatment for patients with advanced non-small cell lung cancer who do not respond to platinum-based chemotherapy. We assessed four patients who had non-small cell lung cancer causing severe acute interstitial pneumonia in association with gefitinib. Although two patients recovered after treatment with steroids, the other two died from progressive respiratory dysfunction. On the basis of autopsies and bilateral distribution of diffuse ground-glass opacities in chest CTs, we diagnosed diffuse alveolar damage, which was consistent with acute interstitial pneumonia. Patients with interstitial pneumonia also had other pulmonary disorders such as previous thoracic irradiation and poor performance status. Physicians should be aware of the alveolar damage induced by gefitinib, especially for patients with these characteristic features.
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PMID:Severe acute interstitial pneumonia and gefitinib. 1280 76

One year has passed since the launch of a new molecular targeted agent, Iressa (generic name: Gefitinib), in Japan ahead of other countries in the world. Gefitinib is the first selective Epidermal Growth Factor Receptor (EGFR) tyrosine kinase inhibitor. Gefitinib was investigated clinically by a single dose ascending study and 3-day multiple dosing study in male volunteers in the UK initially. On confirmation of tolerability by those studies, 4 Phase I studies were conducted in patients with solid tumours generally known to over-express EGFR, with a result of 250 mg or 500 mg (oral administration) decided to be chosen as the recommended dose for Phase II studies. A Phase II study was then conducted in 9 countries including European countries, Australia, and Japan, using once daily oral dosing regimen. In this study gefitinib demonstrated response rate of 18.4% (19/103), and disease control rate of 54.4% (56/103) in advanced non-small cell lung cancer patients (with 1 or 2 previous chemotherapy regimens) at a dose level of 250 mg/day. Symptom improvement rate, which was determined using lung cancer sub-scale (LCS) for QOL assessment, was 40.3% (27/67), and median time to symptom improvement was 8 days (on the initial assessment). In 3 months after the launch, 39 lung injury deaths of patients were reported including deaths attributed to interstitial pneumonia, which was covered broadly by mass media. It is, however, considered that development of Iressa, the first EGFR tyrosine kinase inhibitor showing effects on solid tumours, for clinical use through assiduous researches on molecular targeted agents has truly great significance. This paper gives an overview covering development history to date, clinical study results, and post-launch safety reports.
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PMID:[Development of novel molecular targeted drug, "Iressa", for the treatment of malignant diseases--its basic and clinical studies]. 1471 82

(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

The objective was to use STI571, a kind of tyrosine kinase inhibitor, to treat acute myeloid leukemia (AML) with Philadelphia chromosome. 2 AML cases with Philadelphia chromosome, were collected to observe effect of STI571. One of them was given STI571 after routine chemotherapy failed to respond to treatment, other case received routine chemotherapy only. Both of them underwent HLA-matched/mismatched sibling hematopoietic stem cell transplantation (HSCT). The results showed that cytogenetic and hematologic CR was acquired in case 1 with STI571 while another one gained hematologic CR by accepting routine chemotherapy. Recovery of hemopoiesis was found at 18 and 11 days after HSCT respectively without serious graft-versus-host-disease. The case 1 has been surviving in disease-free state for 5 months since HSCT. The case 2 died from interstitial pneumonia at 8 months after HSCT. In conclusion, STI571 is one of choice for the treatment of Philadelphia chromosome positive AML.
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PMID:[STI571 used in treating acute myeloid leukemia with Philadelphia chromosome]. 1574 42

(1) There is no standard third-line treatment for locally advanced or metastatic non small-cell lung cancer. (2) Erlotinib, like gefitinib, inhibits the tyrosine kinase activity of the epidermal growth factor (EGF) receptor, and has been licensed for sale in the European Union. (3) A double-blind placebo-controlled trial involving 713 patients who had failed to respond to one or two previous chemotherapy regimens showed that erlotinib increased the median survival time by about 2 months (6.7 versus 4.7 months), without improving the quality of this survival. It is not possible to predict precisely which patients are most likely to respond to erlotinib. (4) In first-line treatment, erlotinib was no more effective than placebo as an adjunct to chemotherapy in 2 trials involving 1079 and 1172 patients. (5) The adverse effect profile of erlotinib seems similar to that of gefitinib, mainly consisting of gastrointestinal disturbances (especially diarrhoea: 54% of patients versus 18% on placebo), skin rash (75% versus 17%), and ocular disorders (conjunctivitis: 12% versus 2%). In the comparative trial of second- or third-line treatment, 0.8% of patients developed interstitial pneumonia. (6) Erlotinib, like gefitinib, is metabolized by the cytochrome P450 isoenzyme CYP3A4, potentially creating a high risk of interactions. (7) In practice, the limited benefit of erlotinib seems to be outweighed by its frequent adverse effects. Erlotinib should therefore only be used in clinical trials designed to identify subgroups of patients in whom the risk-benefit balance may be favourable.
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PMID:Erlotinib: new drug. Non small-cell lung cancer: like gefitinib, no established advantage. 1676 93

Gefitinib is an orally active, epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) that is widely used in the treatment of advanced non-small-cell lung cancer (NSCLC). Erlotinib, which has the same mechanism of action as gefitinib, has been recently approved in Japan. We retrospectively investigated the adverse reactions in 16 patients who had received erlotinib after failure of gefitinib treatment. We examined the adverse reactions that occurred during gefitinib or erlotinib treatment using an electronic chart system. Anorexia was more frequent with erlotinib than with gefitinib treatment. Further, anorexia and diarrhea were significantly more severe with erlotinib than with gefitinib treatment. Most adverse reactions developed earlier during the course of erlotinib treatment than during the course of gefitinib treatment. In one patient who had received gefitinib treatment without pulmonary toxicity, erlotinib had to be discontinued due to the development of interstitial pneumonia. Our findings suggest that adverse reactions such as anorexia and diarrhea should be carefully monitored soon after starting erlotinib in advanced NSCLC patients in whom gefitinib treatment has been ineffective, because these reactions will occur sooner and would be more severe in erlotinib treatment.
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PMID:[Comparative evaluation of adverse reactions between gefitinib and erlotinib treatments in the same patients]. 1969 72

Cytotoxic chemotherapy offers a modest benefit for patients with advanced non-small cell lung cancer (NSCLC), with response rates of 20-35% and median survival of 10-12 months. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), gefitinib and erlotinib are active against lung cancer. In retrospective studies, EGFR-TKI therapy among patients harboring EGFR mutations showed response rates higher than 65% and a median survival of 20-30 months. Gefitinib is well tolerated and less toxic compared to conventional cytotoxic drugs, but gefitinib-related interstitial lung disease (ILD) has been reported as a serious adverse effect. Although the mechanism remains unknown, multivariate analysis revealed male sex, history of smoking, and the coexistence of interstitial pneumonia or pre-existence of pulmonary fibrosis and poor performance status were all significant risk factors. Here, we reported a case of gefitinib pneumonitis with severe hypoxemia and impending respiratory failure who showed poor response to intermediate dose of systemic steroids but good recovery with high-dose pulse therapy.
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PMID:Successful treatment of gefitinib-induced acute interstitial pneumonitis with high-dose corticosteroid: a case report and literature review. 2008 91

Erlotinib (Tarceva) is a human epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor used for treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) after failure of at least one prior chemotherapy regimen. Interstitial lung disease, associated with gefitinib (Iressa) use, has been reported in approximately 1% of patients worldwide. However, the adverse pulmonary effects of erlotinib remain poorly documented. Reviewed English language publications in MEDLINE and PubMed suggest that this report is to be the first case report in English of a histologically-confirmed case of near-fatal interstitial pneumonitis with acute lung injury, associated with erlotinib, in East Asian patients. Physicians are hereby encouraged to promptly evaluate new or worsening pulmonary symptoms so that they can detect early radiographic signs of pulmonary toxicity in patients on erlotinib. If toxicity is confirmed, erlotinib should be discontinued and the patient treated appropriately. The case presented suggests that the outcome of erlotinib-associated pulmonary toxicity with acute respiratory failure may be favorable with adequate early management.
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PMID:Erlotinib-associated near-fatal interstitial pneumonitis in a patient with relapsed lung adenocarcinoma. 2018 1

Erlotinib, a kind of epidermal growth factor receptor tyrosine kinase inhibitor, is a target therapy and approved for the treatment of metastatic non-small cell lung cancer (NSCLC) and advanced pancreatic cancer. Among these EGFR-TKI agents, including gefitinib and erlotinib, the common dose-limiting toxicities are diarrhea, mucositis and skin rash (Acneform eruptions). In addition to the above adverse effects, infrequent but potentially fatal and lethal entity complications include acute interstitial lung disease (ILD) and acute hepatitis. The incidence of EGFR-TKI agents (gefitinib and erlotinib) induced acute hepatitis is rare and hepatotoxicity of EGFR-TKI agent was rarely discussed. The treatment of EGFR-TKI agents induced acute hepatitis remains uncertain and cessation medication is current policy. Here we reported a case of erlotinib induced interstitial pneumonitis and acute hepatitis with clinical appearance of hypoxemia and general weakness, treated with high dose pulse therapy and showed good recovery.
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PMID:Successful treatment of erlotinib-induced acute hepatitis and acute interstitial pneumonitis with high-dose corticosteroid: a case report and literature review. 2172 97

Pulmonary toxicity is rarely seen with most commonly used targeted therapies. The endothelial growth factor receptor (EGFR) small-molecule tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib can cause interstitial lung disease (ILD). BCR-ABL tyrosine kinase inhibitors imatinib and dasatinib can cause pleural effusions. Infusion-related bronchospasm is common with the monoclonal antibodies to EGFR cetuximab and panitumumab, and case reports of bronchiolitis and pulmonary fibrosis have been described. Up to one-sixth of patients taking mammalian target of rapamycin (mTOR) inhibitors get a reversible interstitial pneumonitis. Bevacizumab, the monoclonal antibody to vascular endothelial growth factor (VEGF), has been associated with hemoptysis and pulmonary embolism particularly in patients with squamous cell lung cancer. Infusion-related bronchospasms, acute respiratory distress syndrome (ARDS), and interstitial pneumonitis can be seen with the anti-lymphocyte monoclonal antibodies rituximab, ofatumumab, and alemtuzumab. While most pulmonary toxicities from these therapies are mild and resolve promptly with dose reduction or discontinuation, it is important for the clinician to recognize these potential toxicities when faced with treatment-related complications. Discerning these pulmonary adverse effects may help in making decisions on diagnostic testing and therapy, particularly for those with pulmonary and cardiovascular co-morbidities.
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PMID:Pulmonary toxicities from targeted therapies: a review. 2207 88


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