Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042963 (vomiting)
 31,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A diabetic cat with hyperadrenocorticism had polydipsia, polyuria, ventral abdominal alopecia, thin dry skin, and a pendulous abdomen. Results of laboratory testing indicated persistent resting hypercortisolemia, hyperresponsiveness of the adrenal glands (increased cortisol concentration) to ACTH gel, and no suppression of cortisol concentrations after administration of dexamethasone at 0.01 or 1.0 mg/kg of body weight. Necropsy revealed a pituitary gland tumor, bilateral adrenal hyperplasia, hepatic neoplasia, and demodicosis. Adrenal gland function was concurrently assessed in 2 cats with diabetes mellitus. One cat had resting hypercortisolemia, and both had hyperresponsiveness to ACTH gel (increased cortisol concentration) at one hour. After administration of dexamethasone (0.01 and 1.0 mg/kg), the diabetic cats appeared to have normal suppression of cortisol concentrations. The effects of mitotane were investigated in 4 clinically normal cats. Adrenocortical suppression of cortisol production occurred in 2 of 4 cats after dosages of 25, 37, and 50 mg/kg. Three cats remained clinically normal throughout the study. One cat experienced vomiting, diarrhea, and anorexia.
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PMID:Hyperadrenocorticism in a cat. 355 96

Studies have suggested that both natural and synthetic retinoids have extensive chemopreventive activity against a variety of carcinogens in vivo and in vitro. We have previously shown that growth of human breast cancer cells can be inhibited by retinoids, and retinoic acid-binding proteins have been demonstrated in these cell lines and tumor biopsies. We studied the activity of 13-cis-retinoic acid in the treatment of 18 patients with advanced breast cancer refractory to standard cytotoxic and/or endocrine therapy. Patients began on 0.5 mg/kg and escalated to 8 mg/kg over a one-month period unless toxicity (dry skin, dry mucosa, cheilitis, conjunctivitis) forced dose reduction. All these toxicities responded promptly to dose reduction. Four patients exhibited drug related hypercalcemia, 2 complained of severe earache and several had nausea, vomiting and abdominal cramping. There were no objective responses as defined by standard criteria. One patient with thrombocytopenia secondary to documented marrow involvement demonstrated a recovery of platelet count from 9000 to 110,000. 13-cis-Retinoic acid is not of apparent value in women with heavily pretreated breast cancer.
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PMID:Phase II trial of 13-cis-retinoic acid in metastatic breast cancer. 696 67

In a Nordic multi-centre trial, 583 previously untreated multiple myeloma patients were randomized to receive melphalan-prednisone or melphalan-prednisone+ interferon alpha-2b at a dose of 5 million units subcutaneously, 3 d/week. A quality-of-life study was integrated into the trial, using the EORTC QLQ C-30 questionnaire supplemented with 11 questions concerning interferon toxicity. The questionnaire was completed prior to treatment and after 1, 6, 12, 24, 36 and 48 months. 90% of the patients participated in the quality-of-life study, and 83% completed all questionnaires submitted to them. During the first year of treatment the patients on interferon reported significantly more fever, chills, dry skin, fatigue, pain, nausea/vomiting and appetite loss than the control patients. There was a moderate reduction of the global quality-of-life score and slight, non-significant, reductions of physical, emotional, cognitive, social and role functioning scores. After the first year there were no statistically significant differences in any toxicity, symptom or quality-of-life score, except for an increased frequency of dizziness in the interferon group. As only 60% of the patients remained on interferon after 24 months, our data probably underestimate the potential toxicity of the drug. Although there was no significant survival benefit for the interferon patients, a 5-6 months prolongation of the response and plateau phase duration was observed. However, by intention-to-treat analysis, there was no late quality-of-life benefit for the interferon patients to compensate for the early impairment. Thus, the clinical significance of the plateau-phase prolongation is uncertain.
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PMID:Effect of interferon on the health-related quality of life of multiple myeloma patients: results of a Nordic randomized trial comparing melphalan-prednisone to melphalan-prednisone + alpha-interferon. The Nordic Myeloma Study Group. 875 93

The effect of interferon on the health-related quality of life in multiple myeloma was assessed in two trials carried out by the Nordic Myeloma Study (Group (NMSG). In both trials, the EORTC QLQ-C30 questionnaire, supplemented with 11 items relating to interferon toxicity, was used. The first was a randomized controlled trial (NMSG 4/90) evaluating the addition of interferon alpha-2b to melphalan and prednisone during induction, maintenance and relapse. During the first 12 months, patients on interferon reported more chills, fever, fatigue, pain, nausea/vomiting, appetite loss and dry skin than the control patients, and a slight reduction of global health and quality of life. From 12 months onward there were no significant differences in any score between the two groups. In a later trial (NMSG 5/94) evaluating the effect of high-dose chemotherapy with stem cell support in patients under 60 years of age with newly diagnosed myeloma, interferon was used as maintenance. During the maintenance phase, symptom and toxicity scores were not significantly different from those in control patients under 60 years of age in the previous trial. Thus, interferon appeared to be well tolerated after high-dose chemotherapy with stem cell support.
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PMID:Health-related quality of life and patients' perceptions in interferon-treated multiple myeloma patients. Nordic Myeloma Study Group. 1114 38

A child with neonatal pseudohypoaldosteronism is referred. The diagnosis was delayed and complicated as her parents didn't tell us that her sister had been affected by the same illness. The child was born after premature rupture of membranes at 34 weeks. At birth, her conditions were satisfactory. The general conditions of the child gradually worsened and, though she regularly ate human pastorized bank milk, she didn't gain any weight. After 13 days she appeared dehydrated with marbled dry skin and haloed eyes, hypotonic and hyporeflexic. Her suction became more and more weaker, with frequent regurgitations and vomiting. Laboratory tests pointed out hyponatremia (110 mEq/l) and hyperkalemia (6.8 mEq/l). We were able to establish diagnosis of primary pseudohypoaldosteronism measuring plasma concentrations of aldosterone (> 5000 pg/ml), 17 hydroxyprogesterone (normal) and corticosteroids (normal). The child was then supplemented with sodium chlorure. A gradual improvement of general conditions took place. We assumed that both childrens and mother were affected by a milder form of primary pseudohypoaldosteronism, characterized by an autosomal dominant way of transmission. We found high levels of aldosterone with normal levels of blood salts also in the sister and mother patient's. After the neonatal period, pseudohypoaldosteronism can be only suspected in case of positive family history.
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PMID:[Neonatal pseudohypoaldosteronism: when a denied truth can delay a diagnosis]. 1142 44

In earlier studies it has been reported that patients with carcinoid tumours have a relatively good health-related quality of life (HRQoL) and low levels of anxiety and depression. The aims of this study were (a) to investigate the extent to which psychosocial function changes in patients with carcinoid tumours with time from diagnosis and its possible relation to tumour markers, and (b) to compare the HRQoL of patients with carcinoid tumours with that of healthy Swedish adults. Twenty-four patients reported on HRQoL (the EORTC QLQ-C30), anxiety and depression (the Hospital Anxiety and Depression Scale) five times during their first year of treatment. After one year, improvement in nausea/vomiting, flush and anxiety was reported, but there was deterioration of physical function, an increase in muscular pain and problems with dry skin. Levels of tumour markers were not associated with psychosocial function. Patients reported a lower HRQoL compared with healthy Swedish adults. Thus, deterioration of physical function was not accompanied by a deterioration of emotional function, and levels of tumour markers were not related to patients' HRQoL.
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PMID:Health-related quality of life, anxiety and depression in patients with midgut carcinoid tumours. 1185 81

On May 5, 2003, gefitinib (Iressa), ZD1839) 250-mg tablets received accelerated approval by the U.S. Food and Drug Administration as monotherapy treatment for patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) after failure of both platinum-based and docetaxel chemotherapies. Information provided in this summary includes efficacy and safety results of relevant clinical trials. Effectiveness was demonstrated in a randomized, double-blind, phase II, multicenter trial comparing two oral doses of gefitinib (250 mg/day versus 500 mg/day). Two hundred sixteen patients were enrolled. The 142 patients who were refractory to or intolerant of a platinum and docetaxel comprised the evaluable population for the efficacy analysis. A partial tumor response occurred in 14% (9 of 66) of patients receiving gefitinib 250 mg/day and in 8% (6 of 76) of patients receiving gefitinib 500 mg/day. The overall objective response rate for both doses combined was 10.6% (15 of 142 patients) (95% confidence interval 6.0%-16.8%). Responses were more frequent in females and in nonsmokers. The median duration of response was 7.0 months (range 4.6-18.6+ months). Other submitted data included the results of two large trials conducted in chemotherapy-naive, stage III and IV NSCLC patients. Patients were randomized to receive gefitinib (250 mg or 500 mg daily) or placebo, in combination with either gemcitabine plus cisplatin (n = 1,093) or carboplatin plus paclitaxel (n = 1,037). Results from those studies showed no benefit (response rate, time to progression, or survival) from adding gefitinib to chemotherapy. Consequently, gefinitib is only recommended for use as monotherapy. Common adverse events associated with gefitinib treatment included diarrhea, rash, acne, dry skin, nausea, and vomiting. Most toxicities were Common Toxicity Criteria grade 1 or 2. Interstitial lung disease (ILD) has been observed in patients receiving gefitinib. Worldwide, the incidence of ILD is about 1% (2% in the Japanese postmarketing experience and about 0.3% in a U.S. expanded access program). Approximately one-third of the cases were fatal. Physicians should promptly evaluate new or worsening pulmonary symptoms. If ILD is confirmed, appropriate management includes discontinuation of gefitinib. Gefitinib was approved under accelerated approval regulations on the basis of a surrogate end point response rate. No controlled gefitinib trials, to date, demonstrate a clinical benefit, such as improvement in disease-related symptoms or greater survival. Accelerated approval regulations require the sponsor to conduct further studies to verify that gefitinib therapy produces such a benefit.
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PMID:FDA drug approval summary: gefitinib (ZD1839) (Iressa) tablets. 1289 27

On May 5, 2003, gefitinib (Iressa; ZD1839) 250-mg tablets (AstraZeneca Inc.) received accelerated approval by the United States Food and Drug Administration as monotherapy for patients with locally advanced or metastatic non-small cell lung cancer after failure of both platinum-based and docetaxel chemotherapies. Information provided in this summary includes chemistry manufacturing and controls, clinical pharmacology, and clinical trial efficacy and safety results. Gefitinib is an anilinoquinazoline compound with the chemical name 4-quinazolinamine,N-(3-chloro-4-flurophenyl)-7-methoxy-6-[3-(4-morpholinyl)propoxy]. It has the molecular formula C(22)H(24)ClFN(4)O(3). Gefitinib is often referred to as a "specific" or "selective" inhibitor of epidermal growth factor receptor. Studies demonstrate, however, that gefitinib inhibits the activity of other intracellular transmembrane tyrosine-specific protein kinases at concentrations similar to those at which it inhibits the epidermal growth factor signal. Maximum plasma concentrations resulting from clinically relevant doses are 0.5-1 microM or more, well within the IC(50) values of several tyrosine kinases. No clinical studies have been performed that demonstrate a correlation between epidermal growth factor receptor expression and response to gefitinib. Gefitinib is 60% available after oral administration and is widely distributed throughout the body. Gefitinib is extensively metabolized in the liver by cytochrome P450 3A4 enzyme. Over a 10-day period, approximately 86% of an orally administered radioactive dose is recovered in the feces, with <4% of the dose in the urine. After daily oral administration, steady-state plasma levels are reached in 10 days and are 2-fold higher than those achieved after single doses. Gefitinib effectiveness was demonstrated in a randomized, double-blind, Phase II, multicenter trial comparing two oral doses of gefitinib (250 versus 500 mg/day). A total of 216 patients were enrolled. The 142 patients who were refractory to or intolerant of a platinum and docetaxel comprised the evaluable population for the efficacy analysis. A partial tumor response occurred in 14% (9 of 66) of patients receiving 250 mg/day gefitinib and in 8% (6 of 76) of patients receiving 500 mg/day gefitinib. The overall objective response rate (RR) for both doses combined was 10.6% (15 of 142 patients; 95% confidence interval, 6.0-16.8%). Responses were more frequent in females and in nonsmokers. The median duration of response was 7.0 months (range, 4.6-18.6+ months). Other submitted data included the results of two large trials conducted in chemotherapy-naive, stage III and IV non-small cell lung cancer patients. Patients were randomized to receive gefitinib (250 or 500 mg daily) or placebo, in combination with either gemcitabine plus cisplatin (n = 1093) or carboplatin plus paclitaxel (n = 1037). Results from this study showed no benefit (RR, time to progression, or survival) from adding gefitinib to chemotherapy. Consequently, gefinitib is only recommended for use as monotherapy. Common adverse events associated with gefitinib treatment included diarrhea, rash, acne, dry skin, nausea, and vomiting. Interstitial lung disease has been observed in patients receiving gefitinib. Worldwide, the incidence of interstitial lung disease was about 1% (2% in the Japanese post-marketing experience and about 0.3% in a United States expanded access program). Approximately one-third of the cases have been fatal. Gefitinib was approved under accelerated approval regulations on the basis of a surrogate end point, RR. No controlled gefitinib trials, to date, demonstrate a clinical benefit, such as improvement in disease-related symptoms or increased survival. Accelerated approval regulations require the sponsor to conduct additional studies to verify that gefitinib therapy produces such benefit.
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PMID:United States Food and Drug Administration Drug Approval summary: Gefitinib (ZD1839; Iressa) tablets. 1497 17

(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


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