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)

Patients with non-small-cell lung cancer (NSCLC) were treated with ICE chemotherapy (ifosfamide 2000 mg/m2, days 1-3; carboplatin 300 mg/m2, day 1; etoposide 75 mg/m2, days 1-3) intravenously (i.v.) during the first 3 d of a maximum of four 28 d treatment cycles. Interleukin-3 (IL-3) was administered in cycles 2 and 4 as a daily subcutaneous (s.c.) injection on days 5-18. Cohorts of three patients were treated at dosage levels of 0.5, 1.25, 2.5, 5.0, 10.0 and 15.0 micrograms/kg/d. At 15.0 micrograms/kg/d a 'flu-like' syndrome of myalgias, arthralgias and fatigue was considered dose-limiting. Other toxicities were headache, fever, urticaria, arrhythmia, chills and flushing. Subsequently, nine patients were added to the group receiving 10 micrograms/kg/d. 27 patients received IL-3 after their second course of ICE. At 10 and 15 micrograms/kg/d, IL-3 in cycle 2 was associated with enhanced haematological recovery. Depth of neutrophil nadir and days of neutropenia (ANC < 0.5 x 10(9)/l) were reduced in 9/13 patients and in 8/11 patients, respectively. No effect was seen on platelet nadir or days of thrombocytopenia. IL-3 was well tolerated up to 10 micrograms/kg/d when given as a daily s.c. injection. Results suggest IL-3 as a potential adjunct to chemotherapy, and further studies to explore administration of IL-3 in combination with other cytokines in this setting are warranted.
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PMID:Effect of recombinant human interleukin-3 on haematological recovery from chemotherapy-induced myelosuppression. 798 6

The safety and efficacy of olsalazine sodium was compared to sulfasalazine over 3 months in a multicenter, randomized, double-blind study of 56 children with mild to moderate ulcerative colitis. Twenty-eight children received 30 mg/kg/day of olsalazine (maximum, 2 g/day) and 28 received 60 mg/kg/day of sulfasalazine (maximum, 4 g/day). Side effects were frequent in both groups. Eleven of 28 patients (39%) on olsalazine reported headache, nausea, vomiting, rash, pruritus, increased diarrhea, and/or fever. Thirteen of 28 on sulfasalazine (46%) reported similar side effects and/or neutropenia, and four patients had the drug stopped because of an adverse reaction. After 3 months, 11 of 28 (39%) on olsalazine were asymptomatic or clinically improved, compared to 22 of 28 (79%) on sulfasalazine (p = 0.006). In addition, 10 of 28 patients on olsalazine versus one on sulfasalazine required prednisone because of lack of response or worsening of colitis (p = 0.005). The dose of olsalazine used in this clinical trial was thought to be equivalent to a standard dose of sulfasalazine, but fewer patients on olsalazine improved and a greater number had progression of symptoms when compared to sulfasalazine. Although side effects were slightly less frequent for olsalazine, the number of patients was too small to detect a clinically significant difference.
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PMID:Olsalazine versus sulfasalazine in mild to moderate childhood ulcerative colitis: results of the Pediatric Gastroenterology Collaborative Research Group Clinical Trial. 810 99

Oncologic emergencies can occur in cancer patients who have a good prognosis. In all of them, the challenge to the clinician is to diagnose and treat before irreversible complications occur. In febrile patients with neutropenia, cultures of body fluids should be obtained and therapy should be started immediately with broad-spectrum antibiotics. If spinal cord compression is suspected, either magnetic resonance spectroscopy or complete myelography can be done to confirm the diagnosis. Prompt workup in cancer patients with headaches or seizures may avoid neurologic consequences. For brain metastases, immediate treatment with dexamethasone (Decadron, Dexone, Hexadrol) is indicated. For hypercalcemia, a number of drugs that inhibit bone resorption, resulting in lower serum calcium levels, are now available. Malignant cardiac tamponade is relatively rare but potentially lethal; emergency pericardiocentesis often results in marked improvement.
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PMID:Oncologic emergencies. Treating acute problems resulting from cancer and chemotherapy. 827 94

Ten HTLV-I-associated myelopathy (HAM) patients (four men and six women aged 38 to 58 years) with Expanded Disability Status Scale (EDSS) scores ranging from 4.0 to 8.5 entered an open-label zidovudine study. A high-dosage induction (2 g/d for 4 weeks) was followed by 1 g/d for 20 weeks. Five patients were natives of the Caribbean island Hispaniola, and one each was from Colombia, Cuba, El Salvador, Jamaica, and the United States; all were positive by polymerase chain reaction, and nine had positive Western immunoblots for HTLV-I. Side effects included anxiety, insomnia, gastric upset, anorexia, and loss of taste. Preexisting leg cramps were increased in two and headaches in one. Hemoglobin decreased from a mean of 13.5 to 11.8 g/dl and the hematocrit from 40.7% to 34.9% at 8 weeks, and then stabilized. Neutropenia appeared regularly but did not necessitate drug withdrawal. Mean EDSS scores changed little for the group as a whole, but the seven ambulatory patients improved objectively, with their scores dropping from 5.5 to 4.0 and none worsening. Timed gait improved by at least 50%. Following withdrawal, four of the five who had improved regressed. Zidovudine appears to be safe in subjects with HAM who have no other major health problems and should be investigated further.
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PMID:High-dose zidovudine induction in HTLV-I-associated myelopathy: safety and possible efficacy. 841 77

Zidovudine is a dideoxynucleoside analogue of thymidine. It acts by interfering with viral reverse transcriptase, thereby inhibiting human immunodeficiency virus (HIV) replication. Zidovudine has been shown in clinical trials to prolong survival of patients with acquired immune deficiency syndrome (AIDS) and advanced AIDS-related complex (ARC), and to delay progression to ARC or AIDS in patients with earlier disease. At the present time it is suggested that zidovudine be initiated when the CD4 lymphocyte count is less than 500 cells/mm3. Recent studies have suggested a delay in the development of AIDS in patients with CD4 counts over 500 cells/mm3, but ongoing studies will require confirmation. The adverse reactions associated with zidovudine have been well described. It appears that haematological toxicity is associated with both the dose and stage of disease. Anaemia may present more often within the first 3 months of therapy, whereas neutropenia can occur early or late. Mild headache and gastrointestinal intolerance may occur early and in some cases limit tolerance to the drug. A number of neurological adverse reactions have been reported rarely including seizures and dose-reduction encephalopathy. The most significant late adverse reaction is that of myopathy, which occurs in patients receiving zidovudine for more than 6 months. With careful monitoring, the adverse reactions of zidovudine are manageable and patient tolerance of the medication is acceptable.
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PMID:Zidovudine toxicity. Clinical features and management. 848 Dec 17

Patients with idiopathic, cyclic, and congenital neutropenia have recurrent severe bacterial infections. One hundred twenty-three patients with recurrent infections and severe chronic neutropenia (absolute neutrophil count < 0.5 x 10(9)/L) due to these diseases were enrolled in this multicenter phase III trial. They were randomized to either immediately beginning recombinant human granulocyte colony-stimulating factor (filgrastim) (3.45 to 11.50 micrograms/kg/d, subcutaneously) or entering a 4-month observation period followed by filgrastim administration. Blood neutrophil counts, bone marrow (BM) cell histology, and incidence and duration of infection-related events were monitored. Of the 123 patients enrolled, 120 received filgrastim. On therapy, 108 patients had a median absolute neutrophil count of > or = 1.5 x 10(9)/L. Examination of BM aspirates showed increased proportions of maturing neutrophils. Infection-related events were significantly decreased (P < .05) with approximately 50% reduction in the incidence and duration of infection-related events and almost 70% reduction in duration of antibiotic use. Asymptomatic splenic enlargement occurred frequently; adverse events frequently reported were bone pain, headache, and rash, which were generally mild and easily manageable. These data indicate that treatment of patients with severe chronic neutropenia with filgrastim results in a stimulation of BM production and maturation of neutrophils, an increase in circulating neutrophils, and a reduction in infection-related events.
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PMID:A randomized controlled phase III trial of recombinant human granulocyte colony-stimulating factor (filgrastim) for treatment of severe chronic neutropenia. 849 Jan 66

Fluconazole is a triazole antifungal agent which is now an established part of therapy in patients with immune deficiencies. It is effective against oropharyngeal/oesophageal candidiasis (candidosis) when used orally once daily either as treatment or secondary prophylaxis in patients with AIDS or as treatment or primary prophylaxis in neutropenia associated with cancer therapy. Fluconazole also resolves symptoms in up to 60% of patients with cryptococcal meningitis and AIDS. However, in this infection its efficacy as treatment relative to that of amphotericin B is equivocal, and its major role is as the drug of choice for maintenance therapy following amphotericin B induction. In this regard, fluconazole has been proven superior to amphotericin B and to itraconazole 200 mg/day. Comparisons with other drugs used for the treatment of mucosal candidiasis in patients with AIDS show fluconazole to be superior to nystatin, similar to itraconazole and at least as effective as clotrimazole and ketoconazole; it was more so than the latter azole in 1 study. In patients undergoing chemotherapy or bone marrow transplantation, fluconazole as primary prophylaxis has produced greater clinical benefit than a clotrimazole regimen. The incidence of adverse events appears to be somewhat higher in patients with AIDS compared with HIV-negative cohorts, but the qualitative pattern of events is similar. The most frequent events are gastrointestinal complaints, headache and skin rash: rare exfoliative skin reactions and isolated instances of clinically overt hepatic dysfunction have occurred in patients with AIDS. Issues yet to be clarified include: the use of fluconazole in children with AIDS, in whom results have been promising; its efficacy against other fungal infections encountered in immunocompromised patients; whether the drug influences mortality, as has been suggested by one placebo-controlled trial in patients undergoing bone marrow transplant; and the appropriateness of its potential for use as primary prophylaxis against cryptococcal meningitis in patients with AIDS, where it shows efficacy but there is concern over increasing risk of development of secondary resistance. Notwithstanding these undefined aspects of its clinical profile, fluconazole is now confirmed as an important antifungal drug in the management of fungal infections in patients with immune deficiencies. In patients with AIDS it is the present drug of choice as maintenance therapy against cryptococcal meningitis and is a preferred agent for secondary prophylaxis against candidal infections; it is also a favoured agent for primary prophylaxis in patients at risk because of neutropenia associated with chemotherapy or bone marrow transplantation .
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PMID:Fluconazole. An update of its pharmacodynamic and pharmacokinetic properties and therapeutic use in major superficial and systemic mycoses in immunocompromised patients. 853 53

To assess safety, antitumor response, and immunological and virological activity of interferon-alpha 2a and zidovudine combination therapy in patients with AIDS-related Kaposi's sarcoma, we conducted an open-label, Phase II, multicenter study. Sixty-three patients with biopsy-proven Kaposi's sarcoma and no previous interferon-alpha therapy received zidovudine 600 mg/day and interferon-alpha 2a 18 x 10(6) U/day. The median duration of follow-up was 49 weeks. Of 62 evaluable patients, 25 (40%; 95% confidence interval, 0.28-0.52) showed a complete (26%) or partial (15%) antitumor response. Eight of 30 patients (27%) with < 100 CD4 cells/mm3 and 17 of 32 patients (53%) with > or = 100 CD4 cells/mm3 had a response. The median time to response was 36 weeks. Of the 25 patients with a response, four developed tumor progression. The median duration of response was 22.4 weeks. Eight patients (13%) developed another AIDS-defining event and 13 (21%) died. The major toxicities included anemia (16%), neutropenia (27%), elevated serum transaminases (16%), weight loss (16%), malaise (14%), fatigue (14%), fever (10%), and headache (6%). Therapy with intermediate-dose interferon-alpha 2a and zidovudine resulted in tumor regression in patients with AIDS-related Kaposi's sarcoma who had a wide range of CD4 cell counts; this therapy was relatively well tolerated.
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PMID:A phase II study of recombinant human interferon-alpha 2a and zidovudine in patients with AIDS-related Kaposi's sarcoma. AIDS Clinical Trials Group. 860 Dec 24

Topoisomerase I inhibitors are interesting anti-cancer agents with a novel mechanism of action. We performed a phase I study with intravenous GI147211, a new semisynthetic camptothecin analogue, using a daily x 5 schedule administered every 3 weeks, to evaluate the side-effects and pharmacokinetics of the agent. Patients with a histologically confirmed diagnosis of a solid tumour refractory to standard froms of therapy were eligible for the study. GI147211 was given as a 30 min intravenous infusion daily for 5 consecutive days, repeated every 3 weeks. In subsequent patient cohorts the dose was escalated from 0.3 to 1.5 mg m-2 day-1. Pharmacokinetics analysis was performed on days 1 and 4 of the first course using a validated high-performance liquid chromatographic assay and non-compartmental methods. A total of 19 patients were entered into the study, one patient was not evaluable for toxicity because only one drug administration was given. Eighteen patients received a total of 67 courses through four dose levels. The dose-limiting toxicities were neutropenia and thrombocytopenia at the dose of 1.5 mg m-2 day-1. Nadirs occurred on day 15 and day 15 respectively. Other toxicities were mild and infrequent and included nausea/vomiting, headache and alopecia. The maximal tolerated dose was 1.2 mg m-2 day-1. One partial response was observed in a patient with colorectal cancer. The total plasma clearance was 999+/-184 ml min-1 (range 640-1329). The volume of distribution was 190+/-461 m-2 and the terminal half-life was 3.7+/-1.2 h. The AUC increased linearly with the administered dose. A steep and significant sigmoid relationship was established between the AUC and the percent decrease of ANC. GI147211 is a new topoisomerase I inhibitor that induced dose-limiting neutropenia and thrombocytopenia in this phase I study. The recommended dose for phase II studies with this schedule is 1.2 mg m-2 x 5 every 3 weeks.
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PMID:Phase I and pharmacological study of the new topoisomerase I inhibitor GI147211, using a daily x 5 intravenous administration. 861 74

A large study of tumors of low malignant potential confirmed the favorable survival in this group of patients compared to invasive epithelial ovarian tumors. Only 8% of patients died with recurrent disease after surgery. Patients with stage IA borderline tumors with mucinous histology tended to recur later and carried a poorer prognosis than patients with serous histology and similar stage. The group at highest risk for relapse were age greater than 70, stage II or III tumors, and histology other than serous. Long-term survival in this group was less than 75%. This high-risk group of patients should be targeted for innovative adjuvant treatment strategies. This year several well-designed studies with large sample sizes showed DNA ploidy to be an important new independent prognostic factor in stage I ovarian carcinoma. In patients with well-differentiated early stage ovarian cancer, DNA flow cytometric analysis may indicate subgroups with less favorable prognostic characteristics. This method of analysis may be beneficial in determining the need for additional treatments after surgery for early stage ovarian carcinoma. Recommendations for the definitive management of early stage ovarian cancer awaits completion of current GOG and European randomized prospective studies. Paclitaxel given in combination with platinum-containing agents is an intense area of research for treatment of advanced stage disease. Early data from a prospective randomized trial of patients with advanced ovarian cancer showed a higher response rate and longer disease-free survival in patients treated with paclitaxel and cisplatin compared to a standard regimen of cyclophosphamide and cisplatin. The impact of this treatment on long-term survival awaits maturation of data. Preliminary results evaluating G-CSF in combination with paclitaxel and cisplatin for dose escalation was reported. Paclitaxel, 250 mg/m2, and cisplatin, 75 mg/m2, were the maximally tolerated doses, with peripheral neuropathy or myalgias the dose limiting toxicities. Further studies are now underway to test the effect of dose-response with escalation therapies and to determine the optimal dose and schedule for the management of patients with advanced ovarian cancer. IL-3 significantly ameliorated neutropenia but did not prevent cumulative platelet toxicity in a regimen utilizing high-dose carboplatin. This mild improvement in myelosuppression was obtained at the cost of significant toxicity. Nausea, vomiting, malaise, bone pain, headache, fever, chills and facial flushing were frequent. Intraperitoneal chemotherapy was tested as a means of consolidation treatment for patients after having a negative second-look laparotomy. These treatments were shown to be feasible; however, prospective randomized trials will be necessary to determine a benefit over operative therapy alone. Several studies addressed to problem of residual disease after primary surgery and adjuvant chemotherapy. A large phase II study conducted by the GOG confirmed the activity of salvage cisplatin-based intraperitoneal chemotherapy in patients with small-volume residual ovarian cancer with favorable pretreatment characteristics. Whether intraperitoneal platinum-based therapy represents an advantage over systemic platinum therapy is being addressed in a prospective SWOG study. The use of six additional cycles of CAP for treatment of residual disease after primary treatment of surgery and adjuvant chemotherapy did not significantly improve complete pathological response and survival. Prolonged duration of chemotherapy above six cycles is not likely to impact treatment for residual disease. A regimen of high dose carboplatin was compared to whole abdominal radiotherapy for treatment of residual disease after initial chemotherapy. There was no difference in survival or disease-free survival between treatments.(ABSTRACT TRUNCATED)
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PMID:Gynecological malignancies. 863 1


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