Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pneumonia due to Pneumocystis carinii is an infrequent complication following autologous stem cell transplantation (ASCT) which is associated with a high mortality. Although administration of trimethoprim/sulfa- methoxazole (TMP/SMX) is an effective prophylactic strategy for Pneumocystis carinii pneumonia (PCP), treatment-associated toxicity frequently results in discontinuation of therapy. We have conducted a prospective randomized trial comparing atovaquone, a new anti-Pneumocystis agent, with TMP/SMX for PCP prophylaxis following autologous peripheral blood stem cell (PBSC) transplantation. Thirty-nine patients were studied. Twenty patients received atovaquone suspension and 19 patients received TMP/SMX. The median ages were 44 (range 20-68) and 47 (range 32-63) years, respectively. A similar number of patients with solid tumors (14 vs 15) and hematologic malignancies (five vs five) were treated in each group. Either TMP/SMX (160/800 mg) or atovaquone (1500 mg) was administered daily from transplant day -5 until day -1, discontinued from day 0 to engraftment, then resumed 3 days per week until day +100 post-transplant. The median time to engraftment (ANC >0.5 x 109/l) was similar in both groups. Eighty percent of the patients randomized to atovaquone prophylaxis completed the study. Four atovaquone-treated patients were removed from study; two patients (10%) did not receive a transplant and two patients (10%) were removed due to a protocol violation. None of the 16 patients treated with atovaquone experienced treatment-associated adverse effects. Of the 19 patients randomized to receive TMP/SMX, 55% completed the study. Nine TMP/SMX-treated patients were removed from the study; one patient (5%) did not receive a transplant and eight patients (40%) were removed due to drug intolerance (P < 0.003). The rate of intolerance to TMP/SMX led to the early discontinuation of this randomized trial. Intolerance of TMP/SMX included elevated transaminase levels (n = 1), nausea or vomiting (n = 3), thrombocytopenia (n = 2) and neutropenia (n = 2). All episodes of TMP/SMP intolerance occurred following transplantation after a median duration of 17.5 (range 2-48) days and a median of 7 (range 1-20) doses. Resolution of adverse side-effects occurred in all eight patients within a median of 7 (range 2-20) days following discontinuation of therapy. Neither PCP nor bacterial infections were identified in any of the patients treated. This prospective randomized study demonstrated that atovaquone is well-tolerated for anti-Pneumocystis prophylaxis in autologous PBSC transplant patients intolerant of TMP/SMX.
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PMID:A prospective randomized trial comparing the toxicity and safety of atovaquone with trimethoprim/sulfamethoxazole as Pneumocystis carinii pneumonia prophylaxis following autologous peripheral blood stem cell transplantation. 1051 3

Monoclonal antibodies are receiving ever-increasing utilization in the treatment of hematologic malignancies. Campath-1 antibodies are directed against the surface antigen CD52 that is expressed on virtually all lymphocytes and monocytes. Murine forms, Campath-1G and Campath-1M, have been utilized extensively in allogeneic bone marrow transplants in order to purge the allograft of lymphocytes. The humanized form, Campath-1H, is currently the focus of many clinical trials in hematologic malignancies and autoimmune diseases. The genetically engineered Campath-1H has been utilized in the treatment of lymphomas and lymphoid leukemias with impressive results. T-cell prolymphocytic leukemia, chronic lymphocytic leukemia, and non-Hodgkin lymphomas appear to be particularly good targets for this agent. Campath-1H may be administered intravenously or subcutaneously. Infectious complications are the most significant side effect associated with its usage, with fevers, chills, nausea, and vomiting most common. Antibiotic prophylaxis has made the infectious morbidity associated with Campath-1H more manageable. The efficacy demonstrated in clinical trials and manageable toxicities make Campath-1H an appealing agent in the treatment of hematologic malignancies.
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PMID:Campath-1H monoclonal antibody therapy. 1108 57

Farnesyl protein transferase inhibitors (FTIs) represent a new class of anticancer agents specifically targeting aberrant biologic processes involved with cellular transformation and malignancy. Originally developed to inhibit tumors by preventing activation of oncogenic ras genes via suppression of their posttranslational farnesylation, their anticancer activity appears to stem from their ability to inhibit farnesylation of various proteins that mediate signal transduction, growth, apoptosis, and angiogenesis. The safety, biologic activity, clinical response, and pharmacokinetics of R115777, a potent, orally active FTI, were recently investigated in a phase I dose-ranging study in patients with acute leukemias. Patients with acute myelogenous leukemia (AML), acute lymphocytic leukemia (ALL), or chronic myelogenous leukemia (CML) in blast crisis received R115777 100 mg, 300 mg, 600 mg, 900 mg, or 1,200 mg twice daily for 21 days. Cycles were repeated every 28 to 31 days for up to four cycles. An overall response rate of 29% (10/34 evaluable patients) was observed across all R115777 doses. R115777 was well tolerated; common adverse events included fatigue, increased creatinine, nausea, and neutropenia. Dose-limiting toxicity occurred at 1,200 mg twice daily. Farnesylation of lamin A and HDJ-2, examined as biologic end points, was inhibited by R115777 doses > or = 600 mg twice daily. Pharmacokinetic evaluation suggests that R115777 is concentrated in bone marrow at steady state. The biologic and antitumor activity and favorable tolerability of R115777 support further clinical evaluation alone and in combination therapy in hematologic malignancies.
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PMID:Farnesyl protein transferase inhibitors as targeted therapies for hematologic malignancies. 1152 24

Farnesyltransferase inhibitors (FTIs) target multiple pathways including the Ras pathway implicated in the pathogenesis of some hematologic malignancies. R115777 and BMS-214662, selective FTIs in clinical development, exhibit preclinical activity against cell lines and tumor xenografts with or without ras mutations. Phase I dose-escalating trials at M.D. Anderson Cancer Center have explored the potential of these agents as monotherapy for leukemias and myelodysplastic syndrome (MDS). In 20 patients with MDS, two cycles of oral R115777 for 3 consecutive weeks followed by a 1-week rest produced an overall response rate of 30%, consistent with 29% reported in poor-prognosis acute leukemia or blast-phase chronic myelogenous leukemia (CML). Administration of BMS-214662 as a weekly intravenous infusion produced a decrease in bone marrow blasts of greater than 50% in 23% of patients with acute leukemia or MDS; 18% achieved normalization of blast counts to less than 5%. In both studies, most responding patients did not have ras mutations. The most common side effects at maximum tolerated doses of R115777 (400 mg twice daily) and BMS-214662 (118 mg/m(2) weekly) were myelosuppression and nausea, respectively. Further evaluation of FTIs for hematologic malignancies clearly is warranted. Future research should address whether molecular techniques can identify patients most likely to respond to an FTI, optimal administration schedules for these agents, and the value of incorporating an FTI into combination regimens for difficult-to-treat hematologic malignancies.
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PMID:Clinical development of farnesyltransferase inhibitors in leukemias and myelodysplastic syndrome. 1244 48

Treatment options for leptomeningeal disseminated brain tumors are limited by the lack of effective drugs for intrathecal therapy of non-hematologic malignancies. We report on our experience with an intraventricular therapy consisting of mafosfamide, a preactivated cyclophosphamide derivative, and etoposide. Between May 1994 and 2002, 26 patients aged 2-19 years with various intensely pretreated disseminated brain tumors received intraventricular mafosfamide via an indwelling subcutaneous reservoir. Twenty-three of them received a dose of 20 mg. Mafosfamide was administered once or twice weekly until remission was achieved and every 2-6 weeks thereafter as maintenance therapy for a total of 736 administrations (2-63/patient). Since March 1998, two patients were switched to receive intraventricular etoposide and nine received etoposide alternating with mafosfamide. Etoposide was given at a dose of 0.5 mg x 5 d every 3-6 weeks for a total of 122 courses (1-29/patient). Immediate toxicities such as transient headaches, nausea, and vomiting occurred with mafosfamide but were manageable with premedication. Etoposide did not cause any discomfort. No long-term toxicities attributable to intrathecal therapy as evidenced by magnetic resonance imaging or neurologic evaluation were observed. Since all patients received some sort of concurrent anti-cancer therapy, the efficacy of intrathecal therapy cannot be assessed independently. However, seven of 13 patients evaluable for response by cerebrospinal fluid (CSF) cytology developed CSF dissemination under systemic chemotherapy and cleared their CSF only after administration of intrathecal mafosfamide. In conclusion, intraventricularly administered mafosfamide at a dose of 20 mg and etoposide at a dose of 0.5 mg x 5 d for patients over 2 years of age are feasible and safe and may produce responses.
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PMID:Feasibility of long-term intraventricular therapy with mafosfamide (n = 26) and etoposide (n = 11): experience in 26 children with disseminated malignant brain tumors. 1455 99

Multiple myeloma (MM), a malignancy of the plasma cells, accounts for an estimated 14% of all newly diagnosed hematologic malignancies. Advances in chemotherapy and stem cell transplantation have improved survival rates, but MM remains incurable. Bortezomib (Velcade, Millennium Pharmaceuticals, Inc., Cambridge, MA), a first-in-class proteasome inhibitor, has been approved for patients with MM who have received at least two prior treatments and have demonstrated disease progression on the most recent one. During clinical trials, most side effects were manageable with standard interventions. The most common toxicities were asthenic conditions (fatigue, malaise, and weakness), gastrointestinal disturbances (nausea, vomiting, diarrhea, and constipation), thrombocytopenia, peripheral neuropathy, pyrexia, and anemia. Supportive therapies and strategies for side-effect management can prevent worsening of these symptoms, thereby avoiding dose reductions and treatment delays. Oncology nurses play a key role in ensuring the proper and safe administration of bortezomib and often are the first to identify the signs of side effects. Patient education about anticipated side effects and close monitoring of patients can lead to symptom management interventions that are essential to patient comfort and safety.
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PMID:Bortezomib, a newly approved proteasome inhibitor for the treatment of multiple myeloma: nursing implications. 1551 81

Cytokine-release syndrome is a symptom complex associated with the use of many monoclonal antibodies. Commonly referred to as an infusion reaction, it results from the release of cytokines from cells targeted by the antibody as well as immune effector cells recruited to the area. When cytokines are released into the circulation, systemic symptoms such as fever, nausea, chills, hypotension, tachycardia, asthenia, headache, rash, scratchy throat, and dyspnea can result. In most patients, the symptoms are mild to moderate in severity and are managed easily. However, some patients may experience severe, life-threatening reactions that result from massive release of cytokines. Severe reactions occur more commonly during the first infusion in patients with hematologic malignancies who have not received prior chemotherapy; severe reactions are marked by their rapid onset and the acuity of associated symptoms. Massive cytokine release is an oncologic emergency, and special precautions must be taken to prevent life-threatening complications. This article will present an overview of the etiology and management of cytokine-release syndrome in patients receiving monoclonal antibodies to better prepare oncology nurses to safely care for such patients.
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PMID:Cytokine-release syndrome: overview and nursing implications. 1747 24

To evaluate the antiemetic effects of 5-HT(3) receptor antagonists, we investigated the relationship between condition of food intake and occurrence of nausea and vomiting. We collected data such as sex, age, disease, combination of steroids and central antiemetic agents, eating condition, and vomiting condition from medical records in 33 hematologic cancer patients receiving chemotherapy; combination with 5-HT(3) receptor antagonists. The conditions of food intake and nausea/vomiting were checked at 4 mealtime points (lunch, supper, breakfast, and next lunch) after chemotherapy, and were recorded as 1, 3, or 5 as each condition score. To calculate eating scores and nausea/vomiting scores, the sum of scores from 4 mealtime points was used. We found a significant negative correlation between eating scores and nausea/ vomiting scores (n=62, p<0.01). At eating points in which combination therapy with steroids and central antiemetic agents was not given, antiemetic effects of granisetron, azasetron and ramosetron were compared and revealed that azasetron was the most effective antiemetic agent. This result is in agreement with our previous study predicting antiemetic effects of 5-HT(3) receptor antagonists based on the receptor occupancy theory. This study suggests that eithes receptor occupancy or eating score is a useful indicator for assessment of the efficacy of 5-HT(3) receptor antagonists.
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PMID:[Clinical evaluation of antiemetic effects of 5-hydroxytryptamine receptor type 3 (5HT3 receptor) antagonists based on changes in eating condition in cancer patients receiving chemotherapy]. 1837 83

A significant need exists for effective and well-tolerated treatments for patients with hematologic malignancies. Bendamustine hydrochloride is a novel cytotoxic agent that possesses alkylator and purine-like structural groups, which may confer a unique mechanism of action. Bendamustine recently was approved by the U. S. Food and Drug Administration for the treatment of chronic lymphocytic leukemia (CLL) and currently is being used in clinical trials for a number of hematologic and solid tumors. Bendamustine has demonstrated promising clinical activity in patients with hematologic malignancies and has manageable toxicities when administered as monotherapy or in combination with other agents. In clinical trials, nausea, fatigue, vomiting, fever, diarrhea, constipation, and headache were the most commonly reported nonhematologic side effects. Reversible myelosuppression also was reported. Nurses need to understand the efficacy and safety profiles of bendamustine to educate patients and their families about its use and expected side effects. Knowledge of specific measures for preventing and managing associated side effects and dose modifications is integral to the provision of optimal care.
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PMID:Bendamustine: a novel cytotoxic agent for hematologic malignancies. 1884 36

Objectives of this study were to determine the maximum tolerated dose and to characterize the side effect profile and pharmacokinetics of lenalidomide in patients with advanced refractory solid tumors. Patients were treated on a modified Fibronacci dose escalation scheme with an oral daily dose of lenalidomide. A total of 45 patients with 8 different tumor types were accrued. Doses administered included 5, 10, and 20 mg continuous daily doses, every 28 days (n = 15), later modified to intermittent doses of 15, 20, 25, 30, 35, and 40 mg, with a 21 days-on and 7 days-off schedule, due to observed side effects. Lenalidomide exhibited a linear pharmacokinetics over a wide range of doses with the mean half-life of 3.9 hours. The renal function affected lenalidomide clearance, resulting in 50% reduction in patients with mild renal impairment compared with patients with normal function (CL/F = 243 mL/min). Stable disease was documented in 12 of 44 evaluable patients, of whom 9 patients had prostate cancer. Most frequent grade 1 and 2 toxicities included fatigue, nausea, pruritus/rash, neutropenia, and neuropathy. Grade 3/4 events were predominantly hematologic. Lenalidomide was well tolerated up to a 35-mg/d intermittent dosing schedule at doses higher than previously indicated for hematologic malignancies.
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PMID:Phase I study of oral lenalidomide in patients with refractory metastatic cancer. 1945 3


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