Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report the findings in 21 Belgian patients (12 males and 9 females, median age 61 years) with LGLPD. Symptoms at presentation included infection (n = 9), weight loss (n = 5), asthenia (n = 9), pruritus (n = 2) and arthralgia (n = 7). Four patients were asymptomatic. The main clinical findings were hepatomegaly (n = 5), splenomegaly (n = 8), lymph node enlargement (n = 3) and arthritis (n = 5). All patients had an increased LGL count associated with anemia (n = 12), neutropenia (n = 17), often less than 0.5.10(9)/L (n = 10) and thrombocytopenia (n = 6). Three patterns of lymphocyte surface markers were observed: CD3+CD4-8+ (14 patients), CD3+CD4-8+ (5 patients) and CD3+CD4+8- (1 patient). An abnormal karyotype was found in 2 patients. T-cell receptor gene was rearranged in all cases tested (9/9).
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PMID:Large granular lymphocyte proliferative disease: 21 Belgian cases and review of the literature. 131 80

Since their initial description in 1957, the interferons (IFNs) have been increasingly used to treat a wide array of diseases. Acute adverse effects, i.e. 'flu-like' syndromes, hypo- or hypertension, tachycardia, headache, myalgias and gastrointestinal disorders, occur within the first hour or day after starting treatment. They are seldom treatment-limiting and are easily manageable. Sub-acute and chronic effects develop after several days, usually within 2 and 4 weeks of therapy. The most typical is neurological toxicity, including fatigue/asthenia, and behavioural and cognitive changes. Such symptoms may seriously impair quality of life and result in treatment discontinuation. Seizures have seldom been described. Other infrequent central nervous system adverse effects include vertigo, cramp and oculomotor nerve paralysis. Distal paraesthesias and peripheral neuropathy have been reported. IFN-associated autoimmunity is quite rare but a matter of concern. Biological or clinical manifestations usually require several months to become apparent. Autoantibodies have been shown to develop in most patients but have been inconsistently associated with clinical symptoms of systemic lupus erythematosus, rheumatoid-like arthritis and thyroiditis. Both hypo- and hyperthyroidism have been described but are usually reversible. Other infrequent autoimmune reactions include diabetes, pemphigus and worsening of multiple sclerosis. Although several patients present with a pre-existing autoimmune disorder, no predisposing factor has been clearly established. While hypotension and tachycardia are the most frequent acute cardiovascular complications, a few additional cases of cardiac arrhythmias and myocardial ischaemia have been reported after a short course or several weeks of treatment. These latter complications do not appear to be dose-dependent or age-related. Isolated cases of congestive heart failure have also been described. Mild proteinuria has been observed in 15 to 25% of patients, but acute renal toxicity is uncommon. A transient rise in serum aminotransferase levels is frequently noted during the first stage of therapy, especially in patients receiving the highest dosages. Direct hepatotoxicity is extremely rare. Autoimmune hepatitis, which is ill-diagnosed as chronic viral hepatitis, and de novo induction of autoimmune hepatitis, account for the majority of liver diseases. Haematotoxicity is relatively common but mild to moderate, and develops gradually during the first weeks of treatment. Neutropenia is the most common haematological toxicity, but is usually not dose-limiting and resolves rapidly upon drug discontinuation. Myelosuppression, autoimmune and immune allergic haemolytic anaemias and thrombocytopenias have seldom been described. Cutaneous adverse effects comprised nonspecific erythema and hair loss and, less frequently, vasculitis, local ulcerations at the site of injection and exacerbation of psoriasis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Clinical toxicity of the interferons. 751 63

Docetaxel has been evaluated in six phase I studies involving a total of 234 patients with a wide variety of tumour types (50% had breast or ovarian cancer). The aims of these studies were to determine the optimal dosage schedule of docetaxel for use in subsequent phase II studies, and to characterise the pharmacokinetic and tolerability profiles of docetaxel. Intravenous (i.v.) doses of docetaxel (5-115 mg/m2) were administered in various treatment schedules for a total of 790 courses. Cycles were repeated every 2-3 weeks. Dose-dependent neutropenia was the major dose-limiting adverse effect of docetaxel. Other adverse events reported included hypersensitivity, fluid retention, skin reactions, asthenia and alopecia. Anaphylactoid reactions occurred rarely. No abnormal cardiac activity was detected, and neurological adverse events were mild. Docetaxel 100 mg/m2 administered as a 1 h i.v. infusion every 3 weeks combined acceptable tolerability with complete neutropenic recovery. This dosage schedule was thus considered to be optimal for further investigation in phase II studies.
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PMID:Early clinical studies with docetaxel. Docetaxel Investigators Group. 757 2

Docetaxel (Taxotere) is a new cytotoxic compound with a broad spectrum of activity in preclinical studies. This paper reports a phase II trial in patients with previously-treated small cell carcinoma of the lung. 34 patients received 100 mg/m2 of docetaxel in an intravenous infusion given over 1 h every 21 days. Seven partial responses were reported (25% of 28 evaluable patients). Duration of response was 3.5-12.6 months. Toxicities were predominantly neutropenia, alopecia and asthenia. Docetaxel is a new compound with activity in previously-treated patients with small cell lung cancer, and is suitable for evaluation in combination with other cytotoxic drugs active in this disease.
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PMID:Activity of docetaxel (Taxotere) in small cell lung cancer. The Early Clinical Trials Group of the EORTC. 765 28

The antitumour activity of docetaxel was investigated in patients with advanced malignant melanoma. Docetaxel, 100 mg/m2, intravenous, over 60 min, was administered every 3 weeks. Response evaluation was performed after two cycles. No prophylactic treatment with steroids or antihistamines was given. 38 patients were included, 36 were eligible and evaluable for toxicity and 30 patients were evaluable for response. The main haematological toxicity was neutropenia [17 patients with common toxicity criteria (CTC) grade 4 and 11 CTC grade 3] with nadir after 5-8 days and rapid recovery. The most frequent non-haematological toxicity was generalised alopecia (83% of the patients). Asthenia, malaise and fatigue were also seen in 58%. Skin toxicity was also frequent. Hypersensitivity reactions (erythematous rash, urticaria, blood pressure changes and tachycardia), seen in 42% of the patients, were mild to moderate. Oedema was registered in one fifth of the patients and developed after four or more treatment cycles. The overall response rate in the evaluable patients was 17% (five partial responders). We conclude that docetaxel has activity in advanced malignant melanoma.
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PMID:Docetaxel (Taxotere) in advanced malignant melanoma: a phase II study of the EORTC Early Clinical Trials Group. 765 29

A late phase II clinical study of RP56976 (Docetaxel) was conducted in patients with non-small cell lung cancer. Patients with non-small cell lung cancer in Stage IIIB and Stage IV not previously treated were enrolled. Docetaxel was administered at a dose of 60 mg/m2 based on the results of a phase I and an early phase II clinical study, and the efficacy and safety were examined. Of the 77 patients enrolled, 72 patients were evaluated to have completed the scheduled course of treatment by the Evaluation Committee. A partial response (PR) was seen in 18 patients, and the overall response rate was 25.0%. The response rate classified by clinical stage was 28.0% (7/25) in patients with Stage IIIB and 23.4% (11/47) in patients with Stage IV. Hematological adverse reactions included leukopenia of Grade III or more in 53.3% (40/75) and neutropenia of Grade III or more in 86.7% (65/75) as specified in the Adverse Event Reporting Form proposed by the Japan Society for Cancer Therapy. Other major adverse reactions included alopecia, asthenia, and fever, all of which were tolerable. From these results, the efficacy of docetaxel for the treatment of non-small cell lung cancer was confirmed.
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PMID:[Late phase II clinical study of RP56976 (docetaxel) in patients with non-small cell lung cancer]. 797 22

Rhizoxin is a new anti-tumour agent isolated from the pathogenic fungus Rhizopus chinensis. It has shown broad activity against murine tumour models and is also active against vinca alkaloid-resistant cells. The purpose of our studies was to determine the clinical activity of this compound in patients with advanced breast cancer and melanoma. Based on the results of a phase I study, 2.0 mg m-2 was administered as intravenous infusion over 5 min every 21 days. Nineteen patients were entered into the breast cancer phase II trial and received a total of 50 courses (median 2, range 1-6). Of these, dose reductions were performed in three courses because of leucopenia or stomatitis (1.5 mg m-2, one course; 1.45 mg m-2, two courses). Twenty-six patients were entered into the melanoma trial and received a total of 70 courses (median 2, range 1-12). No dose reductions were required. All patients were eligible for toxicity. Haematological toxicity included neutropenia CTC grade 3 (29/120 courses, 24.2%) and grade 4 (11/20 courses, 9.2%). Only drug-related CTC grade 1 thrombocytopenia was observed. Non-haematological toxicity included alopecia in all patients after two courses of treatment as well as CTC grade 3/4 stomatitis and asthenia. In the breast cancer study, one patient achieved a more than 50% tumour reduction after six cycles but was progressing after 6 weeks. Another patient showed a partial remission after the first course but was taken off the study because of CTC grade 3 skin toxicity. One patient was not evaluable for response (early death). No objective remissions were observed in 15 evaluable patients. In melanoma, no objective remissions were observed. We conclude that rhizoxin can be safely administered at 2.0 mg m-2 every 3 weeks. However, it has little activity in patients with advanced breast cancer and melanoma.
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PMID:Phase II clinical trials with rhizoxin in breast cancer and melanoma. The EORTC Early Clinical Trials Group. 856 49

The safety of docetaxel (Taxotere) has been evaluated in the safety overview population consisting of 1070 patients recruited to phase II trials. These patients received a total of 4989 cycles of therapy (median four cycles per patient). Since docetaxel is known to be metabolized in the liver, hepatic impairment was predicted to be a risk factor for increased toxicity and was studied prospectively, comparing the 42 patients in the overview population with moderate hepatic impairment with the 1028 patients with liver function within normal limits. Hepatic dysfunction was associated with an increase in the percentage of cycles of therapy during which febrile neutropenia occurred and the number of patients suffering documented infection and severe (grade 3/4) stomatitis. The incidence of toxic death was also increased in patients with moderate hepatic impairment. The severity of fluid retention, a cumulative toxicity of docetaxel, was found to be reduced, and its onset delayed, by prophylactic treatment with corticosteroids for 5 days, starting 1 day before docetaxel administration. Treatment with corticosteroids was also recommended to reduce the incidence and severity of hypersensitivity reactions and cutaneous toxicities. The most frequent severe non-haematological toxicity of docetaxel was asthenia. Other non-haematological toxicities were generally mild or moderate.
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PMID:Optimal use of docetaxel (Taxotere): maximizing its potential. 886 7

Gemcitabine (2',2'-difluorodeoxycytidine) is a novel nucleoside analogue. As part of a series of studies to determine the maximum tolerated dose (MTD) of gemcitabine and the most appropriate schedule, a two-centre phase I study of gemcitabine was undertaken in patients with advanced refractory solid tumours using a once every 2 weeks schedule. Fifty-two patients were entered into the study at 14 different dose levels (40-5700 mg m-2). Weekly evaluations for toxicity were performed and the MTD for this once every 2 weeks schedule was 5700 mg m-2. The dose-limiting toxicity was myelosuppression, with neutropenia being most significant. Other toxicities were nausea, vomiting, fever and asthenia. One minor response was seen in a heavily pretreated breast cancer patient treated at 1200 mg m-2. Preclinical studies suggest that the efficacy of gemcitabine is more schedule than dose related, and it is concluded that this is not the most appropriate dosing schedule for gemcitabine. However, this study demonstrates the safety profile of gemcitabine, as doses over fourfold greater than that recommended for the weekly schedule of 1000 mg m-2 could be tolerated.
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PMID:Phase I study of gemcitabine using a once every 2 weeks schedule. 940 Sep 47

Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) is one of the most important new drugs used in the treatment of solid tumors. Use of paclitaxel, however, is associated with some toxicity. The main adverse side effects include myelotoxicity, neurotoxicity, hypersensitivity reactions, and asthenia. Toxicity seems to be schedule dependent. Currently, paclitaxel is routinely administered via 3- or 24-hour infusions. This study was performed to evaluate the toxicity and pharmacokinetics of a 1-hour infusion. Thirty-four patients with incurable solid tumors were included. Dose levels were escalated from 150 to 250 mg/m2. Thirty-four patients received a total of 105 courses of paclitaxel. The dose-limiting toxicity was World Health Organization grade 3 neuropathy at a dose of 250 mg/m2 in two of three patients. Two patients were not evaluable for dose-limiting toxicity because treatment was stopped after fewer than three courses due to disease progression. Neither had experienced a dose-limiting toxicity. Other toxicities were World Health Organization grade 1/2 neutropenia, asthenia, myalgia, arthralgia, and grade 1 hypersensitivity. Twenty-one patients were evaluable for preliminary anticancer efficacy. A partial response was observed in five patients (24%), stable disease in three (14%), and progressive disease in 13 (62%). The maximum tolerated dose was established at 250 mg/m2. A dose of 225 mg/m2 is recommended for further phase II trials. There was considerable interindividual and some intraindividual variability in pharmacokinetic parameters. Paclitaxel pharmacokinetics were linear up to 225 mg/m2, while a slightly overproportional increase in the peak plasma concentration and the area under the concentration-time curve was observed at 250 mg/m2, suggesting that paclitaxel's pharmacokinetic characteristics may be nonlinear at higher doses.
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PMID:Phase I study of paclitaxel administered as a 1-hour infusion: toxicity and pharmacokinetics. 942 59


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