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 conducted a phase I study to evaluate the activity and tolerability of concurrent docetaxel and cisplatinum radiosensitization with hyperfractionated irradiation, in patients with advanced non-small cell lung cancer (NSCLC) and squamous cell carcinoma of the head and neck (SCCHN). Nine patients (5 stage III(A) and 4 III(B)) with NSCLC, and 15 with SCCHN (10 stage III and 5 IV) were treated with a b.i.d. hyperfractionated (HF) radiotherapy schedule. The normalized total dose for alpha/beta ratio = 10 Gy was 69.6 Gy for NSCLC and 80.5 Gy for SCCHN patients. The standard dose of cisplatin (10 mg/m(2)) was given combined to docetaxel on a weekly basis. The docetaxel starting dose level was 10 mg/m(2)/week and was escalated by 3 mg/m(2) increments in cohorts of 8 patients (5 SCCHN and 3 NSCLC). DLT (grade 3 malaise) was observed in 4 out of 8 patients treated at the 16 mg/m(2)/week docetaxel dose level. The 13 mg/m(2)/week docetaxel dose level was defined as the MTD causing grade 3 mucositis in 4 out of 8 patients. In total 4 (17%) patients developed grade 3 neutropenia. G-CSF support was given in 1/8, 4/8, and 5/8 patients treated at the 10, 13 and 16 mg/m(2) docetaxel dose levels respectively. Fatigue was the most common adverse event (5/24: 21%) and was responsible for more than 1 week treatment delay in 4 out of 8 patients treated at the 16 mg/m(2)/week docetaxel dose level. Nine (3 NSCLC and 6 SCCHN patients: 37.5%) had treatment delay of 1 week, while 7 (3 NSCLC and 4 SCCHN: 29%) had delays of 2 weeks for combined chemoradiation sequelae. Acute hypersensitivity reactions occurred in 3 (12.5%) patients, and grade 3 mucositis in 2/8, 5/8 and 6/8 patients, treated at 10, 13 and 16 mg/m(2)/week docetaxel dose levels respectively. The overall response rate was 79% (CI = 63-96%) with 33% and 53% CRs for NSCLC and SCCHN patients respectively. There were 3 deaths among 9 NSCLC and 4 among 15 SCCHN patients. Local and/or distant disease recurrences were shown in 4 NSCLC and in 6 SCCHN patients; 5 NSCLC and 9 SCCHN patients are alive with no evidence of tumor progression at 8.5 months mean follow-up time. Radiosensitization with docetaxel and cisplatin given concurrently with HF (b.i.d.) radiotherapy on a weekly basis is a promising approach and the recommended dose for further phase II studies is 10 mg/m(2)/week for both drugs. The antitumor activity shown was significant in both types of tumors. The incorporation of docetaxel in chemoradiotherapy regimens for future treatment of squamous cell carcinoma of the lung and head and neck, merits evaluation in phase II and III trials.
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PMID:A phase I trial of weekly docetaxel and cisplatinum combined to concurrent hyperfractionated radiotherapy for non-small cell lung cancer and squamous cell carcinoma of head and neck. 1246 68

TIN (ifosfamide 1.5 g/m2 daily for 3 days, paclitaxel 175 mg/m2, and nedaplatin 70 mg/m2 on day 1) was administered to patients with metastatic urothelial cancer previously treated by platinum-based chemotherapy and repeated every 4 weeks. Four patients received maintenance therapy, which consisted of 5'-DFUR 800 mg/day orally for 12 weeks and 1 subsequent course of TIN. This therapy regimen was repeated for 2 years from initiation of TIN. Eleven of 12 patients (91.6%) demonstrated a major response (3 complete responses, 8 partial responses), with durations of response ranging from 3 to 20 months. Progression-free survival time was from 0 to 20 months (median 8 months). One-year progression-free survival rate was 45.8%. Overall survival time was from 2 to 20 months (median 10.5 months). One-year overall survival rate was 53.5%. Grade 3/4 hematologic toxicity involved neutropenia in 100% and thrombocytopenia in 33.3%. Febrile neutropenia was observed in 5 patients (41.6%). Grade 3 nonhematologic toxicity involved malaise in 15.3%. No patient discontinued this therapy because of complications. TIN is a potent, well-tolerated regimen for previously treated patients with urothelial cancer.
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PMID:[Paclitaxel, ifosfamide, nedaplatin (TIN) for patients with metastatic urothelial cancer]. 1511

We conducted a phase II study to evaluate the efficacy and safety of cladribine (2-chlorodeoxyadenosine [2-CdA]) for patients with refractory or relapsed indolent B-cell lymphoma or mycosis fungoides. Forty-five patients were enrolled, and 43 patients, including 34 with follicular lymphoma, were eligible. 2-CdA was given by continuous intravenous infusion at a dose of 0.09 mg/kg daily for 7 consecutive days, and this schedule was repeated every 4 weeks up to a maximum of 6 cycles. The overall and complete response rates were 58.1% (25/43; 90% confidence interval, 44.5%-70.9%) and 14.0% (6/43), respectively. The disease progression-free proportions of all 43 eligible and all 25 responding patients at 2 years were 30.3% and 48.1%, respectively. Neutropenia and thrombocytopenia of grade 3 or 4 were observed in 53.3% and 37.8% of patients, respectively, with prolonged cytopenia observed in patients with increased numbers of treatment cycles. Nonhematologic toxicities of grade 3 or greater included diarrhea, arrhythmia, malaise, and gastrointestinal bleeding in 1 patient each, an increase in glutamic-pyruvic transaminase level in 2 patients, and infection in 5 patients. Two treatment-related deaths were observed. Four patients developed myelodysplastic syndrome (MDS) at 13 months to 2 years after completion of the 2-CdA treatments. 2-CdA is an active agent with acceptable toxicity for refractory or relapsed indolent lymphoma; however, prolonged myelosuppression and the potential development of MDS should be carefully monitored.
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PMID:Durable response but prolonged cytopenia after cladribine treatment in relapsed patients with indolent non-Hodgkin's lymphomas: results of a Japanese phase II study. 1554 Sep 3

Intravenous immunoglobulin (IVIg) is administered for various indications and generally considered a safe therapy. Most of the adverse effects (AEs) associated with IVIg administration are mild and transient. The immediate AEs include headache, flushing, malaise, chest tightness, fever, chills, myalgia, fatigue, dyspnea, back pain, nausea, vomiting, diarrhea, blood pressure changes, tachycardia, and anaphylactic reactions, especially in IgA-deficient patients. Late AEs are rare and include acute renal failure, thromboembolic events, aseptic meningitis, neutropenia, and autoimmune hemolytic anemia, skin reactions, and rare events of arthritis. Pseudohyponatremia following IVIg is important to be recognized. Renal failure, usually oliguric and transient, occurs mostly on using sucrose-containing products owing to osmotic injury. Among high-risk patients who have a previous renal disease, dehydration, diabetes mellitus, advanced age, hypertension, hyperviscosity, or are treated by other nephrotoxic medications, administration of a non-sucrose-containing IVIg product after accomplishing hydration, in a low concentration and a slow infusion rate while supervising urine output and kidney function, is recommended. Thromboembolic complications occur because of hyperviscosity especially in patients having risk factors including advanced age, previous thromboembolic diseases, being bedridden, diabetes mellitus, hypertension, dyslipidemia, or those receiving high-dose IVIg in a rapid infusion rate. Immediate AEs can be treated by the slowing or temporary discontinuation of the infusion and symptomatic therapy with analgesics, nonsteroidal anti-inflammatory drugs, antihistamines, and glucocorticoids in more severe reactions. Slow infusion rate of low concentration of IVIg products and hydration, especially in high-risk patients, may prevent renal failure, thromboembolic events, and aseptic meningitis.
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PMID:Intravenous immunoglobulin: adverse effects and safe administration. 1639 92

We evaluated the safety and maximum tolerated dose of interferon (IFN)-alpha2b in combination with protease inhibitor-based highly active antiretroviral therapy (HAART) in a phase 1 study in 14 patients with AIDS-associated Kaposi sarcoma (KS). Planned IFN dose levels were 0, 1, 5, 10, and 15 million IU administered by daily subcutaneous injection. Dose-limiting toxicities were neutropenia and malaise. The maximum tolerated IFN dose was 5 million IU/d. The median CD4 count increased from 260 cells/muL at baseline to a maximum on-study value of 359 cells/muL. In 6 patients with paired baseline and on-study values, the median HIV RNA level decreased from 20,179 copies/mL to a minimum on-study value of 309 copies/mL. Of 13 patients whose KS response could be evaluated, 5 showed objective tumor regression. Responses occurred in HAART-experienced and HAART-naive subjects. Five patients, including 2 responders, 2 with stable KS, and 1 with progression, had serial measurements of Kaposi sarcoma herpesvirus (KSHV) load. None of these patients, irrespective of treatment arm or KS response, showed durable clearance of KSHV from plasma or peripheral blood mononuclear cells. This study establishes a safe dose of IFN that can be used with HAART and, potentially, with other inhibitors of KS in future clinical trials.
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PMID:Interferon-alpha2b with protease inhibitor-based antiretroviral therapy in patients with AIDS-associated Kaposi sarcoma: an AIDS malignancy consortium phase I trial. 1639 45

The primary objective of this study was to determine the response rates of a combination of gemcitabine and cisplatin in unresectable hepatocellular carcinoma (HCC) in Indian patients. The secondary objectives were to evaluate the toxicity, time to progressive disease and overall survival for this combination. Chemonaive patients with histopathologically proven, bidimensionally measurable, stage Ill or IV unresectable HCC were enrolled into this study. All the patients were required to have a Zubrod's performance status not greater than 2, should not have undergone prior radiotherapy and were required to have adequate major organ function. Patients received gemcitabine (1250 mg/m2 intravenously over 30 to 60 min) on days 1 and 8, and cisplatin (70 mg/m2 intravenously over 2 hours) on day land every 21 days. Response assessment was done by a Computed Tomography scan after every two cycles of chemotherapy. From May to December 1999, 30 patients were enrolled in the study; they were all eligible for efficacy and toxicity analysis. Six (20%) patients achieved a partial response and 13 (43%) patients demonstrated stable disease with 11 (37%) patients showing disease progression. The median time to progression was 18 weeks (range 1 to 74 weeks) and the median duration of response was 13 weeks (range 4 to 68 weeks). The 1-year survival rate was 27% and the median overall survival was 21 weeks (95% CI: 17 to 43 weeks). WHO grade 3 and 4 anemia was seen in 11 (37%) and 2 (7%) patients, respectively. Four (13%) patients each experienced grade 3 and 4 neutropenia and grade 3 and 4 thrombocytopenia was seen in 2 (7%) patients each. Major, non-hematologic toxicities were grade 4 elevated bilirubin levels and grade 3 oral toxicity, in 1 patient (3%) each. This regimen was well tolerated and did show activity in Indian patients with advanced unresectable HCC. There is a need to further evaluate this combination in order to define its role in the treatment of HCC.
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PMID:A phase II study of gemcitabine and cisplatin in patients with advanced hepatocellular carcinoma. 1651 57

Whereas neutropenia is common after solid-organ transplantation, graft-vs-host disease is unusual, especially after simultaneous pancreas-kidney transplantation. Most cases reported in the literature give few details of treatment approach, and all were fatal. A 45-year-old man with diabetes underwent simultaneous pancreas-kidney transplantation at our center, with organs from a female donor. Two weeks postoperatively, he was readmitted with fever, malaise, and neutropenia. A bone marrow biopsy specimen demonstrated that two-thirds of the lymphocytes were of female karyotype. Graft-vs-host disease was diagnosed. Aggressive immunosuppression therapy was administered; however, the patient died. To our knowledge, this is the first case report with specific details of a treatment protocol and sequential short tandem repeat data.
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PMID:Treatment of acute graft-vs-host disease after simultaneous pancreas-kidney transplantation: a case report. 2109 80

The antithyroid drugs mainly include thioimidazole (carbimazole, methimazole=thiamazole) and propylthiouracil. After absorption, carbimazole is rapidly metabolized to methimazole and thus switching between these two drugs should not be considered in case of side effects. Furthermore, in case of side effects, sometimes even cross reactions between thioimidazoles and propylthiouracil occur. Common and typical adverse reactions of antithyroid drugs include dose dependent hypothyroidism and thus thyroid function should be repeatedly checked while the patient is on antithyroid drugs. Furthermore, pruritus and rash may develop. In this case, one might try to switch from thioimidazoles to propylthiouracil or vice versa. Antithyroid drugs may cause mild dose dependent neutropenia or severe allergy-mediated agranulocytosis, which typically occurs during the first three months of treatment, has an incidence of 3 per 10,000 patients and cross reactivity between thioimidazoles to propylthiouracil may occur. Rarely, antithyroid drugs can cause aplastic anemia. Mainly propylthiouracil, but sometimes also methimazole may lead to an asymptomatic transient increase in liver enzymes or to severe, even lethal liver injury of cholestatic or hepatocellular pattern. Since propylthiouracil associated liver injury was observed increasingly among children and adolescent, it has been suggested to prefer thioimidazoles for these patients. Because of these potential serious adverse effects, physicians should advise patients to immediately seek medical help if they get a fever or sore throat or malaise, abdominal complaints or jaundice, respectively. Furthermore, arthralgias may develop in 1-5% of patients under both antithyroid drugs. Since arthralgias may be the first symptom of more serious immunologic side effects, it is recommended to stop the antithyroid drug in this case. Drug induced polyarthritis mainly develops during the first month of therapy, whereas ANCA-positive vasculitis is generally observed only after long term exposure to propylthiouracil or very rarely with the thioimidazoles. The teratogenic risk of the thioimidazoles is somewhat higher (Aplasia cutis congenita), that is why one generally recommends preferring propylthiouracil during pregnancy. During breast feeding both, thioimidazoles or propylthiouracil, may be administered. Nowadays, perchlorate is only used short term in case of latent hyperthyroidism before administering iodine-containing contrast agents. Therefore, the known side effects, which usually are only observed after long term treatment, are not an issue any more.
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PMID:[Pharmacotherapy of hyperthyreosis--adverse drug reactions]. 2165 88

Cases of fungal infections are being encountered more often in clinical practice. The factors associated with a high risk of mycoses include, among others, corticosteroidotherapy, the administration antibiotics with wide spectrum of antibacterial properties, neutropenia, neoplasms. Fungi may play a role in cancer formation, may act as a complication in the course of treatment, and may mimic a neoplastic process by giving a similar clinical picture. In the case of fungal throat infection, patients complain of increased body temperature, a general feeling of weakness, malaise, headache, spontaneous pain intensifying during swallowing, a feeling of an obstacle in the throat or a cough. A physical examination may reveal congestion of the mucosa followed by a unilateral crater ulceration often covered with fat, as well as a thick coating, which is accompanied by foetor ex ore. The submandibular and neck lymph nodes are often greatly enlarged and painful. These symptoms may resemble those associated with the neoplastic process and changes in the course of systemic diseases (agranulocytosis). A correct diagnosis in these cases is necessary for adequate therapy. Chronic lymphocytic leukemia (CLL) is the most common type of leukemia among adults in Europe and North America. It is estimated that in Poland, CLL affects approximately 1,400 people per year. In this paper, a case of 62-years old patient with CLL with fungal infection of oral cavity and throat is presented.
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PMID:Difficulties associated with the diagnosis of mycosis of the oral cavity and throat in chronic lymphocytic leukemia (CLL). 2216 36

Leukopenia has a high incidence and is usually a reason for additional testing. Benign ethnic neutropenia is a relatively common cause of neutropenia in the negroid population. It can be the cause of aberrant laboratory results in negroid patients. A 55-year-old woman from Ghana was referred to the outpatient clinic because of malaise, leukopenia and neutropenia. Viral infection, haematological malignancy, auto-immune disease and vitamin deficiency were considered, but could not be confirmed by additional testing. Upon further investigation, the neutropenia in this patient was found to have existed for years. Moreover, our patient's son also had asymptomatic leukopenia. Therefore, benign ethnic neutropenia was considered the most likely diagnosis. Serological analysis of the patient's erythrocytes revealed the absence of Duffy (Fy) blood group antigens Fy(a) and Fy(b), which is associated with benign ethnic neutropenia.
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PMID:[Benign ethnic neutropenia; an unrecognised cause of leukopenia in negroid patients]. 2272 32


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