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:C0042963 (vomiting)
31,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The new fluorinated adenine analog, fludarabine, has been tested for efficacy in many tumor types over the past ten years. Two other similar nucleoside analogs are currently available for commercial use. Cytarabine is used principally as an antileukemic agent, and vidarabine as an antiviral. Unlike vidarabine, fludarabine is resistant to deactivation by adenosine deaminase. Data from Phase I and II trials suggest that fludarabine is potentially effective in a number of leukemias, including acute lymphocytic leukemia, acute nonlymphocytic leukemia, and chronic lymphocytic leukemia (CLL). Unfortunately, the doses required to achieve adequate response in the acute leukemias (greater than 75 mg/m2) were above the maximum tolerated dose, resulting in intolerable granulocytopenia, thrombocytopenia, and a life-threatening neurotoxic syndrome. In CLL: however, the dose required to achieve a satisfactory response is well within tolerated limits. Long-term survival statistics are not yet available, but historical perspective strongly correlates response to other agents with increased survival times. Toxicities seen at dose regimens of 15-40 mg/m2/d for five consecutive days include somnolence, metabolic acidosis, confusion, fatigue, nausea, vomiting, increase in serum creatinine and aminotransferase concentrations, and pulmonary and hepatic abnormalities. Mild to severe hematologic toxicity has been observed at all dose levels.
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PMID:Fludarabine: a review. 206 37

Two hundred sixteen patients with unresectable non-small cell lung carcinoma were randomly allocated to receive etoposide (120 mg/m2, days 1-3) either alone or in combination with high-dose cisplatin (60 mg/m2, days 1-2). The patients' distribution and characteristics were similar in the two treatment arms. The objective response rate for etoposide was 7% versus 25.8% for etoposide plus cisplatin (P less than 0.005). Median progression-free survival in etoposide arm was 3.5 months versus 5 months in the combination arm (P = 0.43). The median survival time for etoposide was 6 months compared with 8 months for etoposide combined with cisplatin (P = 0.87). Significantly more nausea/vomiting (P less than 0.005), serum creatinine elevation (P less than 0.005), hearing loss and/or tinnitus (P less than 0.005), peripheral neuropathy (P less than 0.005), leukopenia (P less than 0.025), and anemia (P less than 0.005) occurred in the etoposide plus cisplatin arm. No statistically significant difference was recorded between the two arms in terms of performance status changes. In conclusion the addition of high-dose cisplatin to single-agent etoposide significantly increases the chance of obtaining tumor response in advanced non-small cell lung cancer at the cost of an increased toxicity without any significant long-term impact on survival and progression-free survival.
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PMID:Etoposide versus etoposide plus high-dose cisplatin in the management of advanced non-small cell lung cancer. Results of a prospective randomized FONICAP trial. Italian Lung Cancer Task Force. 216 39

cis-Diamminedichloroplatinum(II) (CDDP) was given as a single agent at a dose of 25 mg/m2 daily for 5 days by continuous infusion; treatment was repeated every 4 weeks in 30 previously untreated patients with advanced non-small-cell lung cancer (NSCLC). The median age of the patients was 61 years; 13 patients had limited disease and 17, extensive disease. The overall response rate was 40% (12/30; 95% confidence limits, 23-58%), with a median survival of 8 months. Vomiting was observed in 37% of patients; elevated serum creatinine levels (greater than 1.5 mg/dl), in 7%; leukopenia (less than 3,000/mm3), in 39%; thrombocytopenia (less than 70,000/mm3), in 26%; and anemia (hemoglobin less than 9.5 g/dl), in 60% of patients. In all cases, these toxicities were mild and transient, requiring no dose modification. The exposure to filterable platinum, determined from the area under the concentration-time curve, was 9.08 +/- 3.21 micrograms h ml-1. We conclude that CDDP given by 5-day continuous i.v. infusion is safe and effective for treatment of NSCLC.
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PMID:Phase II study of 5-day continuous infusion of cis-diamminedichloroplatinum(II) in the treatment of non-small-cell lung cancer. 217 93

Preclinical evidence has suggested that disulfiram (DS) and related compounds can decrease the toxicity and enhance the therapeutic index of cisplatin (CP). To study this further, we have performed a prospective randomized study wherein 53 patients with CP-sensitive malignancies were assigned to therapy with CP 100 mg/m2 alone (group I) or CP 100 mg/m2 and oral DS 2,000 mg/m2 (group II). Both groups were comparable with regard to sex distribution, age, performance status, prior chemotherapy, and radiotherapy. Twenty-three patients were not evaluable for response (3 refused follow-up, 18 had less than two courses, one had an early death, and one had excessive toxicity during the first cycle of treatment). Of the 30 evaluable patients (16 in group I, 14 in group II), only one in group II achieved a complete response. There was no statistically significant difference in response rate, time to progression, or median survival between the two groups. Fifty-two patients (98.1%) were evaluable for toxicity. Significant differences in toxicities were observed between the two groups: patients in group I encountered lower [Eastern Cooperative Oncology Group (ECOG) 0-1)] grades of nausea, vomiting, and ototoxicity, and patients in group II experienced higher grades (ECOG 2-3) of toxicity in general. In addition, there was no difference in nephrotoxicity between the two groups, as measured by the change in serum creatine or 24-h urine creatinine clearance over the first course of treatment. We conclude that, contrary to previously published reports, DS does not afford significant nephroprotection against CP and, in fact, enhances gastrointestinal and ototoxicities.
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PMID:A randomized phase II study of cisplatin alone versus cisplatin plus disulfiram. 218 Feb 71

The clinical course of 48 children (27 boys and 21 girls) with multicystic kidney dysplasia was analysed retrospectively. The patients were seen and treated at the Children's Hospital of Medical School Hannover between 1976 to 1989. There was no familial occurrence of the disease, yet in eight families various other renal diseases could be observed. In 20 patients the diagnosis of multicystic renal dysplasia was presumed by prenatal sonographic examination, in the other patients the diagnosis was established at the age between 1 day to 12 years. The first manifestations were palpable abdominal mass (n = 16), urinary tract infection (n = 4), casually because of a sonographic evaluation for other reasons (n = 4) and vomiting (n = 2). Associated malformations were found in 18 patients: cardiac malformations (n = 6), dysplasia of the other kidney (n = 5), ureter obstruction of the other kidney (n = 3), horseshoe kidney (n = 1) and others (n = 3). There was no hypertension and serum creatinine levels were normal in those children, who did not suffer from associated malformations of the other kidney. The multicystic kidney was removed operatively in 42 patients at the age of 3 days to 9.5 years (median 4 weeks). The prognosis of multicystic kidney dysplasia depends on associated renal and other malformations.
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PMID:[Multicystic kidney dysplasia]. 219 70

A drug schedule has been devised based on a strategy of G2 blockade followed by prolonged infusion of tubulin-binding agents. The regimen consists of doxorubicin 32 mg/m2 i.v. and cyclophosphamide 320 mg/m2 i.v. on day 1 followed by vinblastine (0.3 to 1.2 mg/m2/day), cisplatin (3 to 12 mg/m2/day), and vincristine (0.04 to 0.16 mg/m2/day) by continuous intravenous infusion on days 5 to 12. Courses are repeated every 28 days. Eighteen patients with advanced solid tumors received 37 courses of chemotherapy in a pilot study to determine safe drug concentrations for the three-drug infusion for 7 days. Dose limiting toxicity was myelosuppression. Patients who received prior mitomycin-C experienced more profound thrombocytopenia than those who did not. Nonhematologic toxicities included mild nausea, vomiting, and transient elevations of serum alkaline phosphatase and serum creatinine. One patient with squamous cell carcinoma of the esophagus who erroneously received vincristine 0.8 mg/m2 instead of 0.08 mg/m2 for 4 1/2 days developed transient myalgia, ileus, and a transient peripheral neuropathy; the patient achieved a sustained complete remission for 15 months and died of unrelated causes. Minor responses and stable disease were seen in two patients with renal cell carcinoma (1 and 2.5 months), three patients with colorectal carcinoma (1.5, 2, and 4 months), and one patient with squamous cell carcinoma of the tongue (2 months). The ViVACCy drug regimen can be given without undue toxicity and may be active in solid tumors.
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PMID:ViVACCy--a drug schedule based on G2 blockade and prolonged infusion of multiple tubulin-binding agents. A pilot study. 219 39

Intracranial pressure (ICP) was continuously monitored in a thirty-two-year-old female of acoustic neurinoma complicated with chronic renal failure. Severe headache with vomiting has begun to appear during hemodialysis for several months, prompting a diagnosis of an obstructive hydrocephalus. Continuous ventricular drainage was placed after admission and changes of ICP were monitored during hemodialysis. Dynamic changes of electrolytes, protein, sugar, urea nitrogen, and creatinine levels in the cerebrospinal fluid (CSF) as well as osmolarity were measured every one hour during the hemodialysis. An increment of ICP started to occur gradually after initiation of hemodialysis reaching the maximum value 23 minutes later. It was spontaneously decreased to the initial level 8 minutes later followed by fluctuations thereafter consisting of the changes of 20 to 30 mmHg. A remarkable rise in osmotic pressure in CSF has been observed corresponding to the rise of ICP which created a large difference from the blood osmotic pressure that consistently decreased following the onset of hemodialysis. Whereas, the absolute values of all measured factors including electrolytes and urea nitrogen in CSF have decreased consistently which did not seem to contribute intermittent increment of osmotic pressure of CSF. The cause of ICP increment in our case was considered mainly due to increase of water content in the brain tissue caused by the widening of osmotic gradient between the CSF and blood, although the substances responsible to the actual increase of CSF osmotic pressure remained unclear.
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PMID:[Elevation of intracranial pressure during hemodialysis--continuous measurement of cerebrospinal fluid pressure in a patient with acoustic neurinoma]. 220 42

Experience with high-dose cytosine arabinoside (HDAC) in pediatric solid tumors is limited. Sixteen children with solid tumors resistant to conventional therapies were registered in a pilot Pediatric Oncology Group (POG) study that required the administration of HDAC at 3 g/m2 every 12 hours for four doses. There were four cases of rhabdomyosarcoma, two cases of fibrosarcoma, four cases of neuroblastoma, and one case each of germ cell tumor, Wilm's tumor, retinoblastoma, hepatocellular carcinoma, Ewing's sarcoma, and Burkitt's lymphoma. All eligible patients had advanced diseases and had previously received extensive chemotherapy. Thirteen patients received one course of HDAC and three patients received two courses of HDAC. Due to prior treatments, patients had less than normal marrow reserves. Short-term toxicity included nausea, vomiting, suppression of hemopoiesis, drug fever, and increased blood urea nitrogen (BUN), creatinine, and liver enzymes. All evaluable patients recovered from their toxicities. There were no drug-related deaths. None of the patients had neurologic problems, including the only patient with prior irradiation to the skull. With the above schedule, HDAC appears to have manageable toxicity.
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PMID:Toxicity of high-dose cytosine arabinoside in the treatment of advanced childhood tumors resistant to conventional therapy. A Pediatric Oncology Group study. 222 60

On the basis of previous studies supporting that glutathione (GSH) reduced cisplatin nephrotoxicity we have designed a new regimen in the treatment of advanced colorectal cancer, which included GSH as a modulator of cisplatin-induced toxicity. Eleven untreated patients with measurable metastatic colorectal cancer received 5-fluorouracil (750 mg/m2, daily continuous infusion for days 1-5) and cisplatin (40 mg/m2 1 hour-infusion for days 6-8) given every 4 weeks. Reduced glutathione (2.5 g) was delivered i.v. prior to each cisplatin infusion. Toxicity was minimal and reversible and included nausea/vomiting (11 cases), mild neurotoxicity (4 cases) and leukopenia (2 cases); only 2 patients showed moderate and transient increases of serum creatinine (less than 2 mg/dl) and BUN. Renal function impairment was also monitored by magnesemia levels and urinary marker enzymes indicating minimal cumulative nephrotoxicity. Out of 10 evaluable patients, only 2 partial responses were observed. The median survival was 9 months (range 5-26). The study was closed, since the preliminary results do not suggest any therapeutic advantage in adding cisplatin to 5-fluorouracil in the present schedule, even using an intensive regimen. Indirect evidence suggests that these disappointing results are not the consequence of interference of GSH on the cytotoxic efficacy of cisplatin. The lack of incidence of severe toxicity of this regimen supports the role of reduced glutathione as a potential protective against cisplatin nephrotoxicity. Although these preliminary results suggest that further studies with the present regimen in this disease are not warranted, in view of its safety this program deserves evaluation in the treatment of neoplastic diseases responsive to 5-fluorouracil/cisplatin.
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PMID:A feasibility study of high-dose cisplatin and 5-fluorouracil with glutathione protection in the treatment of advanced colorectal cancer. 228 98

A phase II trial of intermittent high-dose recombinant interleukin-2 (rIL-2) was initiated to evaluate the response rate, remission duration, and toxic effects in patients with measurable metastatic renal cell carcinoma. The rIL-2 was administered as a bolus intravenous infusion at a dose level of 10.0 x 10(6) U/m2 three times weekly, preceded by indomethacin (50 mg orally). Dose reductions of rIL-2 for hypotension and other grade 3 or 4 toxic effects were permitted. Forty-four patients were entered and 41 were eligible. Previous treatment included nephrectomy (23 patients), radiation therapy (seven), and hormone therapy (three). Most toxic effects observed were moderate and included nausea, vomiting, anorexia (85%); hypotension (85%); fever, chills (78%); central nervous system changes (24%); myelosuppression (27%); and creatinine elevation (15%). Four instances of grade 4 toxicity were observed and included nausea, vomiting with dehydration; hypotension; and myocardial infarction. Thirty patients (73%) required dose adjustments because of toxicity. Five responses (12%) were seen, which included one complete and four partial. Sites of response included lung, liver, and soft tissue; the duration of response ranged from 2 to 20+ months. These results demonstrate that this schedule of rIL-2 can be administered in an outpatient setting, and can produce tumor regression in patients with metastatic renal cell carcinoma, including durable complete responses.
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PMID:Phase II trial of high-dose intermittent interleukin-2 in metastatic renal cell carcinoma: a Southwest Oncology Group study. 229 24


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