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)

Mucormycosis is a rare but invasive opportunistic fungal infection with increased frequency during chemotherapy-induced neutropenia. The clinical infections due to Mucor include rhinocerebral, pulmonary, cutaneous, gastrointestinal and disseminated diseases. The first two are the most common diseases and all entities are associated with a high mortality rate. Still hepatic involvement of Mucor is rarely reported. We experienced a case of hepatic and small bowel mucormycosis in a 56-year-old woman after induction chemotherapy for B-cell acute lymphocytic leukemia. Initial symptoms were a high fever unresponsive to broad spectrum antibiotics and pain in the left lower abdominal quadrant. It was followed by septic shock, deterioration of icterus and progressively elevated transaminase. An abdominal CT demonstrated multiple hypodense lesions with distinct margins in both lobes of liver and pericolic infiltration at small bowel and ascending colon. Diagnosis was confirmed by biopsy of the liver. The histopathology of the liver showed hyphae with the right-angle branching, typical of mucormycosis. The patient was managed with amphotericin B and operative correction of the perforated part of the small bowel was performed. However, the patient expired due to progressive hepatic failure despite corrective surgery and long-term amphotericin B therapy.
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PMID:Hepatic and small bowel mucormycosis after chemotherapy in a patient with acute lymphocytic leukemia. 1089 81

A phase II study to evaluate the efficacy and toxicity of the combination of vinblastine, paclitaxel and cisplatin (PVC) in previously untreated patients with advanced transitional cell carcinoma. Chemotherapy naive patients with locally advanced or metastatic transitional cell carcinoma received the intravenous combination of paclitaxel 175 mg/m(2)over three hours followed by cisplatin 70 mg/m(2)over 3 hours on day 1 and vinblastine 3 mg/m(2)as a bolus on days 1 and 8 on a 21-day cycle, to a maximum of 6 cycles. The day 8 vinblastine was omitted if the total neutrophil count was <1.0. 15 patients (13 M, 2 F) of median age 66 (54-75) received a median of 5 cycles of treatment. There were two complete responses (13%; 95% CI 2-40%) and five partial responses (33%; 95% CI 12-62%), for an overall response rate of 46% (95% CI 21-73%). Responses occurred only in those with locally recurrent tumours and/or lymph nodes involved. Neutropenia at Grade 3-4 occurred in 14 of 67 cycles (21%) resulting in 7 episodes of neutropenic sepsis. Grade 3-4 thrombocytopenia was not observed. Other Grade 3 toxicity included alopecia (10 pts), diarrhoea (2 pts), constipation resulting in bowel obstruction (2 pts), nephrotoxicity (1 pt), myalgic pain (1 pt) and peripheral neuropathy (1 pt). Six patients developed Grade 2 paraesthesia. The median time to progression was 6 months and the median survival was 11 months. The regimen PVC was both less effective against transitional cell carcinoma and less toxic than expected. This may reflect an inhibitory interaction between vinblastine and paclitaxel and this schedule cannot be recommended for further investigation.
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PMID:Evidence for a schedule-dependent deleterious interaction between paclitaxel, vinblastine and cisplatin (PVC) in the treatment of advanced transitional cell carcinoma. 1110 54

In a phase III trial, 191 patients aged over 70 with stage IIIB/IV non-small cell lung cancer were randomized to receive best supportive care (BSC) alone or BSC plus vinorelbine on days 1 and 8, q 21 days for up to six cycles. Increasing difficulties in recruitment meant that the investigators, blinded to the results, stopped the trial early. Data from 161 patients have been analyzed. The vinorelbine regimen was well tolerated. Grade 3/4 neutropenia occurred in 10% of patients and grade 2/3 anemia in 16%. The principle nonhematological toxicities were constipation and fatigue. An objective response rate was recorded in 19.7% of the 76 patients treated with vinorelbine. The survival experience of these patients was significantly superior to that among control patients. The median duration of survival was longer (28 versus 21 weeks) and patients receiving vinorelbine were significantly more likely to survive to one year (32% versus 14%). The relative risk of death in the vinorelbine group was 0.65 (95% confidence interval: 0.45-0.93). Quality of life was extensively investigated using European Organization for Research and Treatment of Cancer scales. While aspects of quality-of-life issues that were directly related to drug toxicity (such as nausea and constipation) were lower in the vinorelbine group, patients who received vinorelbine fared better than controls on measures related to lung cancer symptoms and pain and on social, cognitive, and physical functioning.
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PMID:The ELVIS trial: a phase III study of single-agent vinorelbine as first-line treatment in elderly patients with advanced non-small cell lung cancer. Elderly Lung Cancer Vinorelbine Italian Study. 1118 97

The binding of camptothecin (CPT) to the DNA-topoisomerase complex is reversible, but it needs to be maintained for maximal inhibitory activity. It is also dependent on the chemical structure of CPT. The lactone form is thought to be necessary for the activity. In human serum, the equilibrium between lactone and carboxylate is in favor of the latter. For these reasons, alternative administration of CPT analogues is being evaluated. The ideal compound would remain in lactone form and would expose the host for long periods of time to its effects. Oral administration of irinotecan (CPT-11) and topotecan (TPT) is discussed by other investigators. We studied oral rubitecan and reported a low lactone to total drug area under the plasma concentration-time curve (AUCP) ratio (14.7%), with low plasma concentration over time despite repeated administrations and the presence of an enterohepatic cycle. Aerosolization of a liposomal formulation of rubitecan is currently under study. Six patients have been treated once a day for 5 days every 3 weeks. The dose was 6.7 micrograms/kg/day. Plasma levels are dose for dose higher than those after oral administration, but the ratio of lactone versus total drug is low. No toxicity was observed. The study will continue with increasing doses and lengths of administration. Intrathecal administration of topotecan has been studied in a phase I trial in children. Doses of 0.4 mg are tolerated without toxicity, and clinical responses have been seen in patients with refractory meningial carcinomatosis. Phase II studies are planned. Intraperitoneal (i.p.) administration of topotecan has been studied in a phase I trial as a 24-hour infusion in 5% dextrose at pH 3.5 every 21 days. Dose-limiting toxicity is 4 mg/m2. Toxic effects are neutropenia, anemia, emesis, fever, and pain. Five of 10 patients with ascites had symptomatic relief. Pharmacokinetic analysis demonstrates a second-order kinetics with elimination half-lives of 0.49 and 2.7 hours. The peritoneal to plasma AUC ratio was 31.2. Intramuscular, transdermal, and subcutaneous administrations have been extensively studied in the mouse.
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PMID:Alternative administration of camptothecin analogues. 1119 99

The prognosis of malignant pleural mesothelioma is poor, with a median survival time from diagnosis of 7 to 17 months. At present there is no standardized treatment of this neoplasia. Between July 1995 and January 1999, 22 patients with malignant pleural mesothelioma were enrolled in our study. The characteristics of patients were: 16 men and 6 women; median age 61 years (range, 49-77 years); stage (according to Butchart): 8 patients stage I, 10 stage II, 2 stage III, and 2 stage IV; cytologic diagnosis in 5 cases and histologic diagnosis in 17 cases. The treatment consisted of mitoxantrone 10 mg/m2 intravenous (IV) or intrapleural (IPL), methotrexate 35 mg/m2 IV, and mitomycin 7 mg/m2 IV on day 1 and repeated every 3 weeks, with mitomycin in alternate cycles (MMM regimen). One complete response (4.5%) (42 months of duration) and 6 partial responses (27.3%) (5, 5, 7, 9, 14, and 19 months of duration) were achieved; the overall response rate (ORR) was 31.8% (95% CI, 12.4-51.3%); 7 patients were stable under this treatment (31.8%). According to the pathologic type, ORR for the only epithelial type was 39.9% (95% CI, 15.2-64.8%). Median time to progression was 6 months (range, 1-22). The overall median survival time was 13.5 months (range, 1-50); the median survival time of responders significantly differed from that of nonresponders (18.0 versus 8.5 months; p = 0.017). This treatment produced a considerable clinical benefit, with improvement of dyspnea (68.4%) and pain (33.3%); 15 of 19 patients (78.9%) with pleural effusion at the time of diagnosis showed an important reduction in pleural fluid during chemotherapy. Hematologic toxicity was the main side effect; World Health Organization grade III to IV of neutropenia, anemia, and thrombocytopenia were observed in 81.8%, 13.6%, and 22.7% of patients, respectively. From the data presented here, this regimen can be considered active in the treatment of malignant pleural mesothelioma.
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PMID:Combination chemotherapy with mitoxantrone, methotrexate, and mitomycin (MMM regimen) in malignant pleural mesothelioma: a phase II study. 1131 88

Oral mucositis is a frequent side effect of myeloablative chemo- and radiotherapy preceding stem cell transplantation. It causes pain, poor food intake, and is a port of entry for infection. We studied whether GM-CSF applied topically in the oral cavity can prevent or ameliorate this mucositis. In 36 consecutive patients undergoing a stem cell transplantation, we performed a double-blind placebo-controlled study of 300 micrograms GM-CSF in a 2% methylcellulose gel daily versus a 2% methylcellulose gel alone. Both were locally applied in the oral cavity. The primary end-point was mucositis as measured by the WHO toxicity scale for mucositis, oral assessment scale, and a subjective pain scale, all scored daily. The secondary end-points were need to give parenteral nutrition and morphine, incidence of fever and infections, and duration of neutropenia and hospitalization. No differences were found in the median subjective pain scores, WHO scores, and oral assessment scores between the placebo and the GM-CSF groups. In both groups, nine patients required morphine for pain control. Ten patients in the placebo group and 11 in the GM-CSF group received parenteral nutrition. Documented infections, use of broad-spectrum antibiotics, and number of days with fever were similar in the placebo and the GM-CSF groups. The duration of neutropenia below 0.5 x 10(9)/l (median 14.5 days in the placebo group versus 17 days in the GM-CSF group) and the duration of hospitalization (28.5 versus 29 days) was also not significantly different. We found no beneficial effect of 300 micrograms GM-CSF dissolved in a 2% methylcellulose gel applied locally for chemo- and radiotherapy-induced mucositis in patients undergoing a stem cell transplantation.
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PMID:Effect of locally applied GM-CSF on oral mucositis after stem cell transplantation: a prospective placebo-controlled double-blind study. 1132 Aug 99

Treatment-related morbidity, and in some cases, mortality, associated with autologous and allogeneic bone marrow transplantation has decreased in the past decade largely due to the use of blood stem cells combined with hematopoietic growth factors. However, these procedures remain morbid, with several series documenting regimen-related injury to the oral mucous membranes, the worst form of toxicity from a patient perspective. The pathophysiology of transplant-related mucositis is related to two major events: direct mucosal basal cell injury leading to atrophy and ulcerations, and local infections that can become systemic, the latter of which are exacerbated by the severe neutropenia accompanying high-dose chemotherapy. Recent investigational agents designed to interfere with these two aspects of mucositis have been developed and are showing promise in early clinical trials. In particular, keratinocyte growth factor (KGF) and interleukin-11 appear active. They increase basal cell proliferation, prevent apoptosis due to the preparative regimen, and appear to ameliorate the mucositis seen with high-dose chemotherapy regimens. Oral, nonabsorbable anti-infective agents are also being tested in an attempt to prevent both local and systemic infections. Devoid of significant side-effects, KGF is now in large phase 2 trials that, if positive, will be a significant advance in promoting less morbid transplants by reducing pain and the risk of secondary infections and thus may reduce supportive care costs.
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PMID:Mucositis associated with stem cell transplantation: current status and innovative approaches to management. 1143 15

Periodontal infection may exacerbate during cancer therapy and may result in oral pain and infection, and systemic infection, which may cause morbidity and can lead to mortality in neutropenic cancer patients. Periodontal disease in head and neck cancer patients treated with radiation therapy may lead to acute and chronic complications. The literature was reviewed by a search of Medline of the National Library of Medicine. The search was conducted to identify publications assessing periodontal disease in cancer patients. In addition, a review of papers referenced in the retrieved papers was conducted to identify additional publications for review. Periodontal disease should be assessed and managed prior to medical treatment of cancer for those with oropharyngeal cancer, and for patients in whom neutropenia may develop during treatment. Pretreatment assessment and management, and maintenance of oral hygiene have been shown to be effective in preventing oral and systemic complications during treatment. A complete oral and periodontal examination is appropriate for all patients planned to receive head and neck radiation therapy and those to be treated with medical protocols that are anticipated to result in neutropenia. Oral and periodontal care must continue following cancer therapy, and requires that the health care provider have an understanding of the malignant disease, oral manifestations of the disease, medical management of the disease, and of the oral complications that may develop.
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PMID:Periodontal disease and periodontal management in patients with cancer. 1159 70

An 8-year retrospective analysis of invasive Aspergillus stomatitis in neutropenic patients with acute leukemia was performed to characterize the epidemiology and clinical features of the infection. Twelve cases of invasive Aspergillus stomatitis were identified with both clinicohistological and microbiological evidence, and the majority of cases were caused by Aspergillus flavus (10 [83%] of 12 patients). The infection was strongly suspected when a neutropenic patient developed persistent fever without a known source, symptoms of gingival pain and facial swelling, and a solitary ulcerating lesion of mucogingiva covered with a gray necrotic pseudomembrane. Aspergillus stomatitis was diagnosed a median 23 days after admission. In all 12 patients, the diagnosis was made during the period of neutropenia. Ten patients (83%) were treated with amphotericin B and surgery and survived with recovery of neutrophils. Two patients died, and disseminated aspergillosis was identified in 1 patient.
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PMID:Invasive Aspergillus stomatitis in patients with acute leukemia: report of 12 cases. 1206 Aug 86

Thirty-nine patients with advanced non-small cell lung cancer, refractory or resistant to platinum or taxanes derivatives were treated on an out-patient basis with vinorelbine 25 mg/m2 intravenous (I.V.) on days 1 and 8 followed by gemcitabine 800 mg/m2 l.V. on days 1 and 8. Chemotherapy was repeated every 3 weeks. The patients were evaluated for response every two cycles of treatment. All 39 patients were assessable for toxicity and 35 were assessable for response. On an intent to treat analysis, only 1 (2.6%) patient achieved a partial response (PR) (95% CI 0.09% to 17.6%); fourteen patients (35.9%, 95% CI 29.45% to 67.4%) had stable disease (SD) and 24 (61.5%) had progressive disease (PD). The median time to tumor progression (TTP) was 4.7 months (range 0.13 to 18.9 months), the median survival time was 7.3 months (range 0.6 to 18.9 months) and the 1-year survival rate was 35%. Clinical benefit response including improvement of PS, dyspnea and anorexia, pain and cough reduction and cessation of hemoptysis and fever was observed in 10% to 50% of patients. Grade 3/4 neutropenia occurred only in 2 (5.2%) patients. Five patients experienced febrile neutropenia, which was successfully treated with G-CSF and broad-spectrum antibiotics. No patient experienced grade 3/4 anaemia or thrombocytopenia. One patient experienced grade 4 fatigue and stopped the treatment. Nausea / vomiting, fatigue, neurotoxicity, diarrhea and fever were mild in the majority of patients and did not result in any clinically significant problem. There were no treatment-related deaths. In conclusion, the combination of gemcitabine and vinorelbine showed low objective response rate in patients previously treated with CDDP/taxanes-containing regimens. This regimen was relatively well-tolerated and was associated with prolonged 1-year survival and improvement in cancer related symptoms. To validate these findings a randomized trial of gemcitabine and vinorelbine versus taxotere or best supportive care is required.
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PMID:An out-patient second-line chemotherapy with gemcitabine and vinorelbine in patients with non-small cell lung cancer previously treated with cisplatin-based chemotherapy. A phase II study of the Hellenic co-operative Oncology Group. 1171 2


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