Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

DAB486IL-2 is a recombinant fusion toxin in which the native receptor binding domain of diphtheria toxin has been replaced with human interleukin-2 (IL-2). It selectively binds and intoxicates only cells that bear the high-affinity receptor for IL-2. In the first clinical trial of a genetically engineered ligand fusion-toxin, we have treated 18 patients with chemotherapy-resistant IL-2 receptor expressing hematologic malignancies with escalating doses of DAB486IL-2. The maximal tolerated dose of a daily intravenous bolus of DAB486IL-2 was 0.1 mg/kg per day for 10 doses, established by asymptomatic, reversible elevations of hepatic transaminases without changes in other tests of liver function. Other mild reversible side effects noted were rash, nausea, elevated creatinine, chest tightness, and fever. Pharmacokinetic analysis showed a monophasic clearance of 5.8 +/- 0.7 minutes with peak levels of 3,549 +/- 1,041 mg/mL at the 0.1 mg/kg dose. Approximately 50% of patients developed an antibody response to diphtheria toxin or DAB486IL-2. The presence of such antibodies did not preclude patients from experiencing an antitumor response as four of the six patients with antitumor effect had detectable antibody titers. Although this was a phase I trial designed to define the safety of DAB486IL-2, remissions were observed in three patients lasting from 5 to over 18 months. The ability to achieve significant tumor reductions in this group of heavily treated patients is encouraging and suggests additional trials are warranted in hematologic malignancies.
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PMID:Phase I trial of an interleukin-2 (IL-2) fusion toxin (DAB486IL-2) in hematologic malignancies expressing the IL-2 receptor. 158 7

Autologous bone marrow transplantation (ABMT) for advanced hematologic malignancies is associated with high relapse rates. Interleukin-2 (IL-2) and lymphokine-activated killer (LAK) cells represent a potentially non-cross-resistant therapeutic modality that might prevent or delay relapses if used early after ABMT at a time when the tumor burden is minimal. However, high-dose chemoradiotherapy and ABMT might increase patients' susceptibility to IL-2 toxicity, and might interfere with immunologic responses to IL-2 in vivo. Therefore, to determine safety, tolerance, and immunomodulatory effects of IL-2 therapy early after ABMT, IL-2 was administered by continuous intravenous infusion to 16 patients 14 to 91 days (median, 33) after ABMT for acute leukemia, lymphoma, or multiple myeloma. Patients were sequentially assigned to escalating IL-2 "induction" doses (0.3 to 4.5 x 10(6) U/m2/d, days 1 to 5), and all patients received a nonescalating IL-2 "maintenance" dose (0.3 x 10(6) U/m2/d, days 12 to 21). Most patients exhibited mild to moderate fever, nausea, diarrhea, and/or skin rash with IL-2 infusions. The maximum tolerated "induction" dose was 3.0 x 10(6) U/m2/d; dose-limiting toxicities were hypotension and thrombocytopenia. All toxicities reversed on stopping the IL-2 infusions, and all patients completed "maintenance." Postinfusion lymphocytosis was exhibited by patients at all IL-2 dose levels. With the higher IL-2 doses, increased percentages of patients' PBMC expressed CD16 and CD56, with augmented lysis of K562 and Daudi, reflecting the induction of natural killer and circulating LAK effector activities. Increased LAK precursor activity was exhibited by patients at all IL-2 dose levels. Thus, the IL-2 therapy regimen was safely tolerated after ABMT, and pronounced immunomodulatory effects were observed with the higher IL-2 doses. These studies support the planned use of IL-2 and LAK cells after ABMT in an attempt to reduce relapses of advanced hematologic malignancies.
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PMID:Toxicity and immunomodulatory effects of interleukin-2 after autologous bone marrow transplantation for hematologic malignancies. 204 62

Chemoradiotherapy-induced toxicity following unmodified allogeneic marrow grafting was studied. Patients with hematologic malignancy (n = 157) received cyclophosphamide (120 mg/kg) followed by single or fractionated total body irradiation (TBI); aplastic anemia patients (n = 41) received only cyclophosphamide (200 mg/kg). Physicians rated mucositis, pain and nausea daily as (0) none, (1) mild, (2) moderate, (3) severe, (4) life threatening. Oral mucositis pain began several days prior to transplant, peaked during the second week after transplant, and declined thereafter. Patients with hematologic malignancies (maximum mean rating of 1.6, day 11) experienced more pain than aplastic anemia patients (maximum mean rating of 0.7, day 6). Nausea peaked before transplant and gradually declined. Nausea was higher (p less than 0.001) in patients with aplastic anemia (maximum mean rating of 1.3, day -2) than with hematologic malignancies (maximum mean rating of 0.9, day -6). There was no significant difference between single dose 1000 cGy and 6-day 1200 cGy irradiation. Recipients of 1575 cGy rather than 1200 cGy TBI had significantly (p less than 0.01) higher levels of pain (mean rating 1.25 and 0.82, respectively) and nausea (mean rating 1.27 and 0.72, respectively). Additional research is needed to determine the predictors, consequences and best methods of controlling these toxicities.
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PMID:Chemoradiotherapy toxicity during bone marrow transplantation: time course and variation in pain and nausea. 265 Jul 88

To provide a systematic analysis of how adverse symptoms of disease and side effects of cancer therapy relate to patient noncompliance with treatment, we interviewed 107 patients with hematologic malignancies at the initiation of therapy and 6 months later to collect information on the type, frequency, and difficulty of unpleasant physical effects experienced. Level of compliance was monitored (biochemically and with self-report) on a monthly basis for oral self administration of allopurinol and prednisone. Appointment-keeping to receive infused chemotherapy was also monitored. Nausea was the most frequent side effect experienced. Nausea, fever, and pain were the most difficult physical effects to tolerate when they occurred. Complex treatment regimens and severe diseases related to reports of more physical effects. Younger patients had a more difficult time dealing with these effects than did older patients. Neither the occurrence, frequency, or difficulty dealing with any of the effects related to noncompliance with either of the two self-administered medications. Difficulty with particular effects did relate to noncompliance with clinic appointments to receive infused chemotherapy.
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PMID:The influence of symptoms of disease and side effects of treatment on compliance with cancer therapy. 318 4

A multicenter prospective randomized trial of four versus six weeks of amphotericin B, 0.3 mg/kg per day, plus flucytosine, 150 mg/kg per day, was performed with 194 patients with cryptococcal meningitis. One or more toxic drug reactions developed in 103 patients: azotemia (51), renal tubular acidosis (two), leukopenia (30), thrombocytopenia (22), diarrhea (26), nausea/vomiting (10), and hepatitis (13). The four- and six-week regimens were complicated by toxicity in 44 percent and 43 percent of cases, respectively. Toxicity appeared during the first two weeks of therapy in 56 percent and during the first four weeks in 87 percent. Azotemia did not occur more frequently in renal transplant recipients or diabetic patients. Cytopenias did not appear more often in patients with hematologic malignancies or those receiving immunosuppressive therapies. Toxic reactions that contributed to death developed in five patients (two with azotemia, one with pancytopenia, one with hepatitis, one with ileus). Amphotericin B-induced azotemia was not a significant risk factor for the subsequent development of bone marrow, gastrointestinal, or hepatic toxicity attributable to flucytosine. Flucytosine toxicity was associated with peak serum flucytosine levels of 100 micrograms/ml or more during two or more weeks of therapy (p = 0.005). Peak 5-fluorouracil levels were not predictive of toxicity. An initial dose of flucytosine is recommended based on the creatinine clearance: 150 mg/kg per day at a creatinine clearance above 50 ml/minute, 75 mg/kg per day at a creatinine clearance of 26 to 50 ml/minute, and 37 mg/kg per day at a creatinine clearance of 13 to 25 ml/minute. The serum creatinine level should be monitored twice weekly and the creatinine clearance weekly during therapy in order to anticipate changes in serum flucytosine concentration. In addition, it is recommended that the serum flucytosine level be determined two hours after an oral dose once a week, and that the dose be adjusted to maintain a level of 50 to 100 micrograms/ml.
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PMID:Toxicity of amphotericin B plus flucytosine in 194 patients with cryptococcal meningitis. 330 26

A case of intestinovesical fistula secondary to leukemic infiltration is described. The patient was known to have chronic lymphocytic leukemia and had been receiving chemotherapy fo ten months. She presented complaining of nausea, vomiting and vague abdominal pain. She initially denied genitourinary tract symptoms, although admitting urinalysis revealed pyuria, hematuria and bacteriuria. Urine cultures repeatedly grew E. coli despite broad spectrum antibiotic therapy. She eventually developed fecalant material in her urine and pneumaturia. Cystoscopy revealed a fistulous tract. At surgery an ileovesical fistula was found and histopathology showed lymphocytic leukemic infiltration. Intestinovesical fistulas are uncommon. Congenital, traumatic, inflammatory and solid neoplastic etiologies are well established in the literature. No previous cases have been attributed to hematologic malignancies. Since higher remission rates and longer periods of remission are being achieved with chemotherapy, and since fistula symptomatology may present quite subtly, awareness of this association may expedite diagnosis.
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PMID:Intestinovesical fistula in a patient with chronic lymphocytic leukemia: case report and literature review. 707 31

This study evaluated the acute toxicity of trimetrexate (TMTX) used in combination with cyclosporine (CsA) for prevention of acute graft-versus-host disease (GVHD) in patients undergoing allogeneic marrow transplantation from HLA-mismatched, related donors. TMTX has a mechanism of action similar to that of methotrexate (MTX); however, unlike MTX, TMTX is not primarily dependent on renal excretion. Patients were conditioned for transplant with cyclophosphamide, anti-thymocyte globulin, and total body irradiation. TMTX, 10 mg/m2 i.v., was administered on days 1, 3, 6, 11, 18, 25, 32, and 39 after transplant. CsA, 1.5 mg/kg i.v., was administered every 12 hr beginning on day-1. Eleven patients with hematologic malignancies or aplastic anemia (median age = 34 yr) received TMTX. Toxicity assessed included nausea, vomiting, fever, rash, time to myeloid and platelet engraftment, mucositis, and hepatic and renal dysfunction. Toxicity of TMTX was not different from that observed with MTX in a similar patient population. One patient died on day 16 before engraftment. The other 10 patients all engrafted and all developed acute GVHD at a median time of 11 days after transplant. The major manifestation of acute GVHD was in the skin, and all but one patient responded to primary therapy with corticosteroids. Seven patients have survived a median of 447 days after transplant. No significant toxicity from TMTX was observed. Further trials are warranted to define the role of TMTX in marrow transplantation.
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PMID:A toxicity study of trimetrexate used in combination with cyclosporine as acute graft-versus-host disease prophylaxis in HLA-mismatched, related donor bone marrow transplants. 762 43

Bisphosphonates are analogues of inorganic pyrophosphate, a naturally occurring chemical in bone. In vitro and animal experiments demonstrated that these agents were effective inhibitors of bone resorption. Subsequently they were applied to a variety of clinical problems in which increased bone resorption was an underlying feature of the pathology. In 1971 etidronate became the first bisphosphonate shown to inhibit bone resorption in humans when it was given to patients with Paget's disease. Subsequently this agent was also found to be useful in treating the hypercalcemia of malignancy. At the present time cyclic etidronate therapy is also used for the prevention of bone loss in patients with osteoporosis and for the prevention of heterotopic ossification in spinal cord-injured patients and in patients after hip replacement. Newer bisphosphonates are generally more potent than etidronate and do not produce a severe mineralization defect as do higher doses of etidronate. Pamidronate and clodronate are highly effective in the management of Paget's disease, hypercalcemia due to malignancy and immobilization, metastatic bone disease, and hematologic malignancies affecting bone. They are also promising agents for the prevention of osteoporosis. Alendronate, risedronate, and CGP 42446 are highly potent bisphosphonates that look very promising for the treatment of all disorders of bone resorption. It is fortunate that adverse reactions are not a prominent feature of bisphosphonate use. The main side effects are nausea and abdominal discomfort, mainly with oral use, a transient increase in bone pain in patients with Paget's disease, and an acute-phase reaction (fever, myalgia, mild leukopenia) in patients receiving aminobisphosphonates. The evolution of bisphosphonate therapy should be considered one of the major therapeutic events of the past 25 years. Future research should define the optimum use of these agents.
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PMID:Bisphosphonates in the treatment of disorders of mineral metabolism. 767 Oct 99

We previously demonstrated in a pilot study that outpatient marrow harvesting is feasible and safe. Here, we provide an update and analysis of 149 outpatient marrow harvests and compare the results with 61 inpatient harvests. The mean patient age was 33 years. Mean outpatient harvest duration was 41 minutes, similar to inpatients. Average pre- and post-harvest hemoglobin values were 122 and 99 g/L, respectively, for outpatients and 119 and 93 g/L for inpatients. Fifty per cent of patients received an average of two units of homologous packed erythrocytes following the procedure versus 2.3 units for 57% of inpatients. Mean harvest volume was 1248 ml (versus 1341 ml for inpatients) and the mean number of mononucleated cells obtained was 2.73 x 10(8)/kg (3.23 x 10(8)/kg for inpatients). There were no serious complications in patients undergoing out-patient marrow harvesting. Sixteen outpatients (11%) had minor complications of hypotension, fever, nausea, vomiting or moderate pain. Thirteen patients (9%) required subsequent admission for a mean of 1.3 days. Eight inpatients (13%) had similar complications. All patients responded well to fluid replacement and analgesics. We confirm the safety of outpatient marrow harvesting for patients with hematologic malignancies.
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PMID:Outpatient bone marrow harvesting: an update. 774 44

Pharmacoeconomic analysis is often based upon incremental cost per increase in survival (cost-effectiveness). Using this definition supportive care measures, which increase quality but not quantity of life, generate a zero denominator and cannot be directly compared with other components of health care cost. Cost-utility analysis, which measures incremental cost per increase in quality-adjusted life-years (QALY), where QALY = utility score x time at risk, addresses this problem, since successful supportive intervention increases the utility score and thus provides a finite denominator in QALY even when absolute survival is unchanged. However, utility scores for various supportive care modalities have not been well defined. As a pilot study to generate a first approximation of a utility score for nausea/vomiting, we used a rating scale technique and administered two visual analogue scale questions to 30 patients completing a cycle of chemotherapy. Patients rated their global quality of life during their previous cycle of chemotherapy with hypothetical absence or presence of nausea/vomiting as the only variable. The study population included 8 male and 22 female patients, with a median age of 56 years. The most common malignancies were breast cancer (8 patients), lung cancer (7 patients), and hematologic malignancies (7 patients). On a 100 mm visual analogue scale, the mean score for overall quality of life during chemotherapy was 79 mm without nausea/vomiting and 27 mm with nausea/vomiting (P < 0.001, paired t-test). The implied marked increase in utility with relief of nausea/vomiting suggests a significant impact on cost-utility analysis. Similar methodology could be used to estimate utility scores in other areas of supportive care.
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PMID:Impact of nausea/vomiting on quality of life as a visual analogue scale-derived utility score. 896 74


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