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)

Dasatinib, a potent inhibitor of BCR-ABL in vitro, is effective for patients with chronic myelogenous leukemia (CML) resistant or intolerant to imatinib. To provide a more definitive assessment of dasatinib in chronic-phase (CP)-CML, we report extended follow-up of a phase II trial, presenting data for the entire patient cohort (N=387). Dasatinib (70 mg) twice daily was administered to patients with imatinib-resistant or -intolerant CP-CML. With median follow-up of 15.2 months (treatment duration, <1-18.4 months), a complete hematologic response was attained or maintained in 91% of patients. A major cytogenetic response (MCyR) was attained or maintained by 59% (52% imatinib resistant and 80% imatinib intolerant); this was complete in 49% of patients (40% imatinib resistant and 75% imatinib intolerant). Of 230 patients achieving an MCyR, 7 experienced disease progression. Fifteen-month progression-free survival was 90% while overall survival was 96%. Grade 3/4 thrombocytopenia and neutropenia were reported in 48 and 49% of patients, respectively. Non-hematologic toxicity (any grade) consisted primarily of diarrhea (37%), headache (32%), fatigue (31%), dyspnea (30%) and pleural effusion (27%). Pleural effusions were classified as grade 3 in 6% of reported events, with no incidence of grade 4. Dasatinib is associated with high response rates in patients with imatinib-resistant or -intolerant CP-CML.
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PMID:Dasatinib induces durable cytogenetic responses in patients with chronic myelogenous leukemia in chronic phase with resistance or intolerance to imatinib. 1840 16

Glycogen storage disease type Ib (GSD Ib, OMIM 232220) is an inborn disorder of glucose metabolism, caused by mutations in the G6PT gene, encoding a glucose 6-phosphate transporter (G6PT). GSD Ib is mainly associated with fasting hypoglycaemia and hepatomegaly. Most GSD Ib patients also show neutropenia and neutrophil dysfunction and therefore are at risk of developing severe infections and inflammatory bowel disease (IBD). An increased risk for autoimmune disorders, such as thyroid autoimmunity and Crohn-like disease, has also been demonstrated, but no systematic study on the prevalence of autoimmune disorders in GSD Ib patients has ever been performed. We describe a 25-year-old patient affected by GSD Ib who developed 'seronegative' myasthenia gravis (MG), presenting with bilateral eyelid ptosis, diplopia, dysarthria, severe dysphagia, dyspnoea and fatigue. The repetitive stimulation of peripheral nerves test showed signs of exhaustion of neuromuscular transmission, particularly evident in the cranial area. Even in the absence of identifiable anti-acetylcholine receptor antibodies, seronegative MG is considered an autoimmune disorder and may be related to the disturbed immune function observed in GSD Ib patients.
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PMID:Myasthenia gravis in a patient affected by glycogen storage disease type Ib: a further manifestation of an increased risk for autoimmune disorders? 1843 26

Purpose. This study investigates the efficacy and toxicity of daily oral etoposide in chemotherapy for non-heavily pretreated advanced and metastatic soft tissue sarcoma (STS).Subjects. Twenty-seven patients with progressive and measurable disease were treated. Median age was 53 years (range 20-71 years) and performance status WHO 0 or 1. Histologies included mainly leiomyosarcoma (8), malignant fibrous histiocytoma (4), rhabdomyosarcoma (4), liposarcoma (2) and synovial sarcoma (2). Fifteen patients had received prior radiotherapy, of whom three included sites with haematopoiesis. All patients had received prior chemotherapy, including adjuvant therapy (7) and mostly consisted of one two-drug schedule (ifosfamide and doxorubicin) or two single-drug regimens.Methods. Chemotherapy consisted of etoposide (VP16-213), 50 mg m(-2) day(-1) x 21 q 4 weeks. Blood cell counts were done weekly. Dose reductions and a maximum delay of 2 weeks was allowed depending on cell counts during treatment and at the start of a new 4-week treatment cycle.Results. No objective response was observed. Progressive disease was observed after two treatment cycles in 17/27 patients (68%) and after three cycles in 22/27 patients (81%). The other patients received three to five cycles. Twenty-four patients went off study due to progressive disease. Grade 3 and 4 neutropenia was observed in eight and one patients, respectively. Thrombocytopenia grade 3 was seen in two patients. Non-haematological toxicity grade 3 (nausea, diarrhoea or alopecia) was observed in three patients, and grade 4 (dyspnea, hypotension or haemorrhage) in three patients.Discussion. No objective response was obtained. Oral etoposide at a dose of 50 mg m(-2) day(-1) x 21 q 4 weeks is inactive in chemotherapy of pretreated STS. Disease progression occurred within three cycles in the majority (81%) of patients. Toxicity of this regimen in non-heavily pretreated patients is low.
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PMID:EORTC Group Phase II Study of Oral Etoposide for Pretreated Soft Tissue Sarcoma. 1852 Dec 9

The targeted therapies sunitinib, sorafenib, temsirolimus, and bevacizumab (when used in combination with interferon-alpha2a) have dramatically improved outcomes for patients with advanced renal cell carcinoma (RCC). Clinical application of these novel agents outside the trial setting, however, may present some challenges for treating individual patients with unique needs. In some patients, dose modifications may be considered for potential drug interactions and for management of severe cases of hematologic or nonhematologic toxicities. The more common grade 3 or 4 side effects with sunitinib and sorafenib include hypertension, fatigue, hand-foot syndrome, elevated lipase, lymphopenia, and neutropenia. Congestive heart failure is a less common but serious side effect that warrants treatment discontinuation. Temsirolimus exhibits a different side-effect profile, with the more common grade 3 or 4 side effects being metabolic in nature (i.e., elevated triglycerides, elevated glucose, hypophosphatemia) as a result of its inhibitory effects on the mammalian target of rapamycin-regulated lipid and glucose pathways. Asthenia, rash, and dyspnea also occur in patients receiving temsirolimus. Virtually all of the side effects associated with these agents can be managed effectively in the majority of patients with medical treatment or supportive interventions. Recognition and prompt management of side effects are important to avoid unnecessary dose reductions that may result in suboptimal efficacy.
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PMID:Targeted therapies for metastatic renal cell carcinoma: an overview of toxicity and dosing strategies. 1883 39

The importance of fungal infection of the lung in immunocompromised patients has increased substantially during the last decades. Numerically the most patients are those with neutropenia, e.g., patients with malignancies or solid organ and stem cell transplantation, chemotherapy, corticosteroid use and HIV infection. Although fungal infections can occur in immunocompetent patients, their frequency in this population is rare. The clinical symptoms such as fever accompanied with non-productive cough are unspecific. In some patients progression to hypoxemia and dyspnea may occur rapidly. In spite of improved antifungal therapy morbidity and mortality of these infections are still high. Therefore an early and non-invasive diagnosis is very important. That is why CT and even better High-Resolution-CT (HR-CT) is a very important modality in examining immunocompromised patients with a probability of fungal infection. CT is everywhere available and, as a non-invasive method, able to give the relevant diagnose efficiently. This paper should give an overview about the radiologic findings and possible differential diagnosis of diverse pulmonary fungal infections in CT. Pneumonias caused by Aspergillus, Cryptococcus, Candida, Histoplasma, Mucor and Geotrichum capitatum are illustrated.
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PMID:[Diagnosis of fungal pneumonia in the thoracic CT]. 1929 67

PURPOSE To compare pemetrexed/carboplatin with a standard regimen as first-line therapy in advanced non-small-cell lung cancer NSCLC. PATIENTS AND METHODS Patients with stage IIIB or IV NSCLC and performance status of 0 to 2 were randomly assigned to receive pemetrexed 500 mg/m(2) plus carboplatin area under the curve (AUC) = 5 (Calvert's formula) on day 1 or gemcitabine 1,000 mg/m(2) on days 1 and 8 plus carboplatin AUC = 5 on day 1 every 3 weeks for up to four cycles. The primary end point was health-related quality of life (HRQoL) defined as global quality of life, nausea/vomiting, dyspnea, and fatigue reported on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 and the lung cancer-specific module LC13 during the first 20 weeks. Secondary end points were overall survival and toxicity. Results Four hundred thirty-six eligible patients were enrolled from April 2005 to July 2006. Patients who completed the baseline questionnaire were analyzed for HRQoL (n = 427), and those who received > or = one cycle of chemotherapy were analyzed for toxicity (n = 423). Compliance of HRQoL questionnaires was 87%. There were no significant differences for the primary HRQoL end points or in overall survival between the two treatment arms (pemetrexed/carboplatin, 7.3 months; gemcitabine/carboplatin, 7.0 months; P = .63). The patients who received gemcitabine/carboplatin had more grade 3 to 4 hematologic toxicity than patients who received pemetrexed/carboplatin, including leukopenia (46% v 23%, respectively; P < .001), neutropenia (51% v 40%, respectively; P = .024), and thrombocytopenia (56% v 24%, respectively; P < .001). More patients on the gemcitabine/carboplatin arm received transfusions of RBCs and platelets, whereas the frequencies of neutropenic infections and thrombocytopenic bleedings were similar on both arms. CONCLUSION Pemetrexed/carboplatin provides similar HRQoL and survival when compared with gemcitabine/carboplatin with less hematologic toxicity and less need for supportive care.
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PMID:Phase III study by the Norwegian lung cancer study group: pemetrexed plus carboplatin compared with gemcitabine plus carboplatin as first-line chemotherapy in advanced non-small-cell lung cancer. 1943 83

Pneumonitis is a rare but serious complication of docetaxel treatment. We report a 63-year-old woman with locally advanced breast cancer who was treated with docetaxel and trastuzumab. After the first course she was admitted with febrile neutropenia that resolved rapidly. After the second course she was admitted again with fever and dyspnoea. Despite intensive treatment she died of respiratory failure three weeks later. Autopsy showed diffuse interstitial inflammation of both lungs consistent with drug-induced inflammation. Docetaxel treatment was the most likely cause. It is important to be aware of this toxicity, because the subtle warning signs can easily be mistaken for an opportunistic infection, and, if not recognised in time, the mortality rate is high.
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PMID:Fatal pneumonitis after treatment with docetaxel and trastuzumab. 1974 95

Fusarium is a fungal pathogen of immunosuppressed lung transplant patients associated with a high mortality in those with severe and persistent neutropenia. The principle portal of entry for Fusarium species is the airways, and lung involvement almost always occurs among lung transplant patients with disseminated infection. In these patients, the immunoprotective mechanisms of the transplanted lungs are impaired, and they are, therefore, more vulnerable to Fusarium infection. As a result, fusariosis occurs in up to 32% of lung transplant patients. We studied fusariosis in 6 patients following lung transplantation who were treated at Massachusetts General Hospital during an 8-year period and reviewed 3 published cases in the literature. Cases were identified by the microbiology laboratory and through discharge summaries. Patients presented with dyspnea, fever, nonproductive cough, hemoptysis, and headache. Blood tests showed elevated white blood cell counts with granulocytosis and elevated inflammatory markers. Cultures of Fusarium were isolated from bronchoalveolar lavage, blood, and sputum specimens.Treatments included amphotericin B, liposomal amphotericin B, caspofungin, voriconazole, and posaconazole, either alone or in combination. Lung involvement occurred in all patients with disseminated disease and it was associated with a poor outcome. The mortality rate in this group of patients was high (67%), and of those who survived, 1 patient was treated with a combination of amphotericin B and voriconazole, 1 patient with amphotericin B, and 1 patient with posaconazole. Recommended empirical treatment includes voriconazole, amphotericin B or liposomal amphotericin B first-line, and posaconazole for refractory disease. High-dose amphotericin B is recommended for treatment of most cases of fusariosis. The echinocandins (for example, caspofungin, micafungin, anidulafungin) are generally avoided because Fusarium species have intrinsic resistance to them. Treatment should ideally be based on the Fusarium isolate, susceptibility testing, and host-specific factors. Prognosis of fusariosis in the immunocompromised is directly related to a patient's immune status. Prevention of Fusarium infection is recommended with aerosolized amphotericin B deoxycholate, which also has activity against other important fungi.
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PMID:Fusarium infection in lung transplant patients: report of 6 cases and review of the literature. 2120 Jan 88

Vinfunine (VFL) is a novel bifluorinated tubulin-targeted agent of the vinca alkaloids class active in advanced stage breast cancer. We conducted a phase I study combining VFL with doxorubicin (DXR) to define the recommended dose (RD), safety, pharmacokinetic (PK) interaction and efficacy. Two schedules (day 1 every 3 weeks; days 1 and 8 every 3 weeks) were investigated as first line chemotherapy in metastatic breast cancer patients. Thirty-two patients received a total of 162 cycles of the VFL-DXR combination (median 6). The RDs were VFL 250 mg/m(2)/DXR 40 mg/m(2) every 3 weeks for schedule 1 and VFL 120 mg/m(2)/DXR 25 mg/m(2) days 1 and 8 every 3 weeks for schedule 2. The main dose-limiting toxicity was neutropenia. The most frequent non-hematological adverse events were nausea, fatigue, constipation, vomiting, anorexia, stomatitis and dyspnea. Objective response rate was reached in 47.1% of the patients. No PK interaction was observed. VFL-DXR combination is feasible with manageable toxicity. The antitumor activity was promising and supports further evaluation.
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PMID:A phase I clinical and pharmacological study evaluating vinflunine in combination with doxorubicin as first line treatment in metastatic breast cancer. 2144 99

A 45-year-old man complaining of cough, dyspnea, and difficulty in swallowing was referred to our hospital. Chest CT scan showed a mediastinal mass compressing the trachea. He was diagnosed with poorly differentiated lung carcinoma by percutaneous needle biopsy. Bronchoscopy and upper gastrointestinal endoscopy revealed a tracheoesophageal fistula (TEF). Long-lasting febrile neutropenia made it impossible to continue chemotherapy, but a course of radiotherapy (total 61 Gy) was completed. The next endoscopy revealed closure of the TEF. Chemoradiotherapy (CRT) has been reported to close TEF in esophageal cancer, but the risk of a CRT-induced worsening of the fistula has dissuaded physicians from using CRT to treat TEF in lung cancer patients. CRT may serve as a palliative treatment for TEF in lung cancer as well as esophageal cancer.
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PMID:Tracheoesophageal fistula closed by chemoradiotherapy in lung cancer. 2176 94


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