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)

Adverse reactions to the drugs employed in the National Cooperative Crohn's Disease Study were sought prospectively at each patient visit and by retrospective review of all patient charts. Prednisone caused evident side effects in over 50% of patients on high-dose suppressive therapy and in approximately one-third of patients on prophylactic dose. Thirty-two percent of patients on high-dose, and 26% on prophylactic-dose prednisone required dose reduction or withdrawal because of side effects. Comparable figures for sulfasalazine were 14% and 12%, and for azathioprine 32% and 20%. The incidence of nausea, vomiting, or anorexia among patients taking sulfasalazine was 46% and 34%, on high and low dose respectively; however, this incidence was no different than that observed among patients taking placebo. These symptoms occasioned withdrawal from the study of only 4% and 3% of patients on high and low doses of sulfasalazine, respectively. Azathioprine produced leukopenia at a dose of 2.5 mg/kg body weight in 15% of patients and the mean white cell count, lymphocyte count, granulocyte count, and hematocrit all fell significantly in patients on this dose. Pancreatitis occurred in 5% of patients taking azathioprine but in no other patients. Sulfasalazine proved to be the safest effective suppressive drug for Crohn's disease. Prednisone toxicity, though substantial, is acceptable in view of its demonstrated suppressive efficacy. Azathioprine was approximately as toxic as prednisone but no more effective than placebo in suppressing active disease. None of the drugs was effective prophylactically, and all showed appreciable long-term toxicity.
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PMID:National Cooperative Crohn's Disease Study: adverse reactions to study drugs. 3 77

Twenty-six evaluable patients with disseminated or locally unresectable pancreatic or biliary tract carcinoma received Ftorafur (4 g/m2 iv day 1 and 22 and 2 g/m2 iv day 4 and 26), Adriamycin (60 mg/m1 IV day 1 and 45 mg/m2 iv day 22) and BCNU (150 MG/M2 IV DAY 1) combination chemotherapy (FAB) repeated at 6--8 week intervals. Two (29%) complete and one (14%) partial remissions were observed in 7 patients with biliary carcinoma while 5 of 19 (26%) patients with pancreatic carcinoma achieved partial remissions. Median survival for responding patients was approximately 11 months (range 7--16+) with median survivals of about 6 months (p less than 0.05 and about 3 months (p less than 0.05) for patients with stable and progressive disease. Major drug toxicity was myelosuppression with median lowest granulocyte counts of 1,000/microliters and platelet counts of 88,000/microliters. Approximately 25% of patients required antibiotic therapy for fever of unknown origin or documented infections. Other tolerable drug toxicities included nausea, vomiting and mucositis. The FAB regimen appears quite promising in biliary tract cancer and has efficacy in pancreatic carcinoma that warrants further clinical trials. Because of myelotoxicity observed with this regimen we now recommend a BCNU starting dose of 100 mg/m2 instead of 150 mg/m2.
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PMID:Adriamycin, BCNU, ftorafur chemotherapy of pancreatic and biliary tract cancer. 38 4

Sixty adult patients with disseminated melanoma refractory to DTIC or Dacarbazine were given chemoimmunotherapy with intermittent high single dose Actinomycin-D and Levamisole. Actinomycin-D was given at a dose of 1.5-2.0 mg/m2 intravenously every 3 to 4 weeks. Levamisole was given in a dose of 150 mg/day for two consecutive days each week (50 patients) and in a dose of 200 mg every other day (10 patients). Antitumor responses consisted of 2% complete remissions (CR), 2% partial remissions (PR), and 33% disease improvement less than PR or stabilization (S). Comparison of these patients who received Actinomycin-D + Levamisole with those on an immediately preceding study in a similar population where Actinomycin-D was given as a single agent revealed no difference in response rates. Patients who responded to Actinomycin-D + Levamisole (CR + PR + S) survived significantly longer (35 weeks) than nonresponders (12 weeks, p less than 0.01). Survival was not longer (p less than .05) in responding patients (CR + PR + S) receiving Actinomycin-D + Levamisole (35 weeks) compared to those responding to Actinomycin-D alone (18 weeks, p = 0.09). Hematologic toxicity was tolerable with median lowest granulocyte counts of 1.6 x 10(3)/microliter and platelet counts of 134,000/microliter. Other toxic effects were predominantly nausea, vomiting, and mucositis. In those patients who received alternate day Levamisole there was greater gastrointestinal upset as well as fever, rash and central nervous system toxicity which was unacceptable.
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PMID:Actinomycin-D, levamisole chemoimmunotherapy of refractory malignant melanoma. 44 22

The first case of interdonor incompatibility associated with granulocyte transfusion is presented. The patient received Kell positive granulocyte transfusions containing about 30 ml of red cells 36 and 132 h prior to receiving a granulocyte transfusion containing anti-Kell 1/128. The chills, fever, vomiting and hypotension resulting from the red cell incompatibility, cleared with appropriate fluid therapy. Antibody detection methods must be applied to each unit of granulocytes. The patients blood should be tested with reagent grade antibody to detect small numbers of antigen-containing cells if an antibody-containing granulocyte transfusion is to be given. Routine major and minor cross-matching is insufficient. Removal of the antibody containing plasma and resuspension of the granulocytes in plasma free of irregular antibodies may be the most effective way to prevent such incompatibility.
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PMID:Interdonor incompatibility as a cause of reaction during granulocyte transfusion. 69 39

During a 4-year period a 28-year-old female had 4 episodes of eosinophilia of over 10,000/mu 1; these episodes were associated with nausea, vomiting, diarrhea, and abdominal pain. On one occasion, she had ascites and pleural effusion which contained numerous mature eosinophils. On each occasion, these attacks disappeared within several weeks without any specific treatment. A diagnosis of eosinophilic gastroenteritis was made. A plasma sample obtained during the eosinophilia generated in vitro eosinophilic colonies when added to granulocyte/macrophage-progenitor (CFU-GM) cultures without exogenous growth factors. Colony formation was inhibited by anti-interleukin-5 (IL-5) antibody but not by antibodies toward IL-3, granulocyte colony-stimulating factor (G-CSF) or GM-CSF. A high plasma interleukin-5 (IL-5) level was noted when measured by enzyme-linked immunosorbent assay, while IL-3, G-CSF, and GM-CSF were undetectable. During remission the plasma gave negative results both for colony formation and IL-5 level. These results indicate that the eosinophilia of this disease is mediated by IL-5.
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PMID:Interleukin-5 in eosinophilic gastroenteritis. 138 Feb 4

Many chemotherapeutic agents have been evaluated during the last 40 years and some have now an established place in the management of malignant disease. However these agents have a level of toxicity well above any other group of drugs. Chemotherapeutic agents do not discriminate between normal and neoplastic tissue. Chemotherapeutic regimens that are toxic to rapidly dividing malignant cells, are liable to be particularly harmful to lymphoid tissues, bone marrow and the epithelium of the gastrointestinal tract. The side effects due to chemotherapy are classified as immediate, early, delayed and late. Immediate side effects are those that may occur within the first 24 hours of treatment. The most common immediate side effect is nausea and vomiting, due to direct central effect on the vomiting center of the brain. Cisplatin and nitrogen mustard are particularly prone to this complication. The antiemetics usually used are metoclopramide, domperidone and steroid. The efficacies of these drugs are not so good for nausea and vomiting due to cisplatin administration, however several blockades against serotonin M-receptor recently developed are quite effective to nausea and vomiting of chemotherapeutic regimens including cisplatin. Early side effects commence within about one month of therapy. The most common is bone marrow toxicity and can occur after therapy with the vast majority of anticancer drugs. The relative importance of leukopenia and thrombocytopenia vary between the drugs and their route of administration. Recently, hematopoietic cytokines, such as granulocyte-colony stimulating factor (G-CSF) and granulocyte-macrophage-colony stimulating factor (GM-CSP) have been introduced to granulocytopenia developed by cancer chemotherapy. In the phase II study of G-CSF, a rapid recovery of granulocytes after chemotherapy and marked efficacy on infection in granulocytopenic patients were observed. In addition to this, autologous bone marrow transplantation after chemotherapy has been described in patients with solid tumors.
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PMID:[Palliative therapy in cancer. 5. Side effects by anticancer drugs and their treatments]. 169 55

Diaziquone (AZQ), a synthetic quinone with demonstrated activity against acute nonlymphocytic leukemia (ANLL), primary CNS tumors, and non-Hodgkin's lymphoma (NHL), is virtually devoid of nonhematopoietic toxicity at conventional doses. As a prelude to its inclusion into bone marrow transplant (BMT) preparative regimens, a phase I study of high-dose AZQ with autologous BMT (ABMT) was performed. Patients with refractory solid tumors and lymphomas were treated with a single 24-hour infusion of AZQ at 50 to 355 mg/m2 in dose escalations of 20%. Fifty-six patients received 69 courses. Those receiving greater than 60 mg/m2 had nadir granulocyte and platelet counts less than 500/microL and 20,000/microL, respectively. Nausea, vomiting, stomatitis, and diarrhea were mild, transient, and not dose-related. Transient minimal elevations of liver function tests were seen in five patients and were also not dose-related. The maximally tolerated dose (MTD) of high-dose AZQ was found to be 245 mg/m2, with nephrotoxicity being dose-limiting. Significant azotemia was seen in four of 12 patients treated at 295 and 355 mg/m2, including fatal anuric renal failure in three of these patients. Reversible proteinuria also occurred in 24 of 26 courses above 150 mg/m2, including nephrotic range proteinuria in eight courses, all at doses of 205 to 355 mg/m2. The proteinuria was also associated with multiple proximal tubular defects including generalized aminoaciduria and proximal renal tubular acidosis. There were six early deaths including two of early renal failure (295 and 355 mg/m2), two of sepsis (205 and 245 mg/m2), one of a pulmonary embolus (85 mg/m2), and one of progressive disease (60 mg/m2). Of 50 patients who were assessable for response, there were seven responses including two of 10 with primary CNS tumors, one of 12 with malignant melanoma, one of five with non-small-cell lung carcinoma, two of two with breast carcinoma, and one of one with ovarian carcinoma. Because of its activity in ANLL and NHL and its unique toxicity spectrum, high-dose AZQ may improve the efficacy of current BMT preparative regimens without significantly increasing their nonhematopoietic toxicity.
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PMID:A phase I trial of high-dose diaziquone and autologous bone marrow transplantation: an Illinois Cancer Council study. 207 48

Forty-two patients with advanced malignancy judged unlikely to respond to standard treatment received high-dose combination chemotherapy with cyclophosphamide, etoposide, and cisplatin in a phase I trial. Twenty-two of these patients who had at least a partial response (PR) to the first cycle of therapy received a second cycle, and eight patients received three or more cycles of therapy. Bone marrow replacement was not used. The maximum-tolerated doses (MTDs) were cyclophosphamide 2.5 g/m2 on days 1 and 2; etoposide 500 mg/m2 on days 1, 2, and 3; and cisplatin 50 mg/m2 on days 1, 2, and 3. Hematologic toxicity was not dose-limiting by study design. Recovery to an absolute granulocyte count above 100/microL occurred at a median of 9 days from onset (range, 3 to 23 days) at the MTD. Recovery was delayed after the third cycle. Only one patient on his third cycle failed to recover peripheral blood counts and died of sepsis an day 43. Hematologic toxicity was not dose-dependent. Nonhematologic toxicities included emesis, fatigue, alopecia, diarrhea, and anorexia and were generally well tolerated. The dose-limiting toxicities were fatal pulmonary or cardiac toxicities in five of nine patients treated at the highest dose level. Patients likely to do well can be selected by tumor type, response to prior therapy, and performance status. Nine of 36 assessable patients had a complete response (CR) and 13 a PR for a response rate of 61%. Five patients (12%) remain alive and free of disease at 15 to 32 months. Repeated cycles of dose-intensive combination therapy can produce long-term disease-free remissions in patients with refractory tumor types. The toxicity of the regimen is acceptable if patients are carefully selected.
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PMID:Phase I study of repeated cycles of high-dose cyclophosphamide, etoposide, and cisplatin administered without bone marrow transplantation. 199 24

Fluorouracil (5-FU) and cisplatin display marked therapeutic synergy in preclinical models and are effective in the treatment of a number of solid tumors when combined and administered intravenously (IV). Each drug has also been administered intraperitoneally (IP) and displays a favorable pharmacologic profile and acceptable clinical toxicity. We therefore undertook a phase I study to determine the feasibility and toxicity of combination IP chemotherapy with these agents. Thirty-one patients with histologically documented malignancy confined to the peritoneal space were treated with cisplatin 90 mg/m2 mixed with 5-FU in 2 L of lactated Ringer's solution and given IP for 4 hours every 28 days. Cohorts of at least three patients received starting 5-FU concentrations ranging from 5 mmol/L (1,300 mg in 2 L) to 20 mmol/L. The dose-limiting toxicity was neutropenia with a median granulocyte nadir of 156 cells per microliter occurring at a 5-FU dose of 20 mmol/L. Intrapatient escalation of the 5-FU dose was permitted and 15 cycles of chemotherapy were delivered at 5-FU concentrations greater than 20 mmol/L, the highest concentration being 30.7 mmol/L (8 g of 5-FU in 2L). Other toxicities included mild to moderate nausea during all cycles of therapy, vomiting in 54% of cycles, and diarrhea in 15% of cycles. Abdominal pain, renal dysfunction, peripheral neuropathy, and oral mucositis occurred infrequently and were not related to the 5-FU dose. Peritoneal fluid and plasma 5-FU concentrations were measured by high-performance liquid chromatography (HPLC) in selected patients. Mean peak plasma 5-FU concentrations ranged from 6.19 mumol/L to greater than 60 mumol/L, and peritoneal fluid to plasma 5-FU area under the curve (AUC) ratios ranged from 85 to 1,150. Nine of 15 patients with nonbulky disease had resolution of malignant ascites or at least a 50% reduction of peritoneal studding by tumor at repeat laparotomy. We conclude that combination IP chemotherapy with cisplatin and 5-FU is technically feasible and has acceptable clinical toxicity and a favorable pharmacologic profile. The recommended starting 5-FU dose for phase II trials is 3,900 mg mixed with 90 mg/m2 of cisplatin in 2 L of isotonic fluid.
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PMID:Phase I clinical and pharmacologic study of intraperitoneal cisplatin and fluorouracil in patients with advanced intraabdominal cancer. 223 Aug 97

Liposome-entrapped cis-bis-neodecanoate-trans-R,R-1,2-diaminocylohexane platinum(II) (L-NDDP) is a new lipophilic cisplatin derivative formulated in a liposomal carrier currently in phase I clinical trials. The preclinical toxicity and pharmacology of L-NDDP were studied in mice and dogs. At the LD50 dose (i.v. bolus) in mice (60.5 mg/kg or 181.5 mg/m2), a tenfold decrease in the granulocyte and platelet counts was observed in the absence of renal toxic effects. In dogs, the maximum tolerated dose (MTD) of L-NDDP given i.v. over a period of 45-60 min was 150 mg/m2. This dose produced significant vomiting (6-18 episodes), minimal renal dysfunction, a maximal decrease in granulocyte and platelet counts of from 30% to 70%, and acute and transient elevation of liver enzymes. Higher doses (225 and 300 mg/m2) resulted in severe gastrointestinal (GI) toxicity in one animal and the death of two others within 48 h. Autopsy results showed multifocal hemorrhages in the lungs, GI tract, kidney, and liver. Three dogs were treated monthly with the MTD up to a cumulative dose of 637.5-712.5 mg/m2 with excellent tolerance. No cumulative myelosuppression or liver dysfunction was observed, whereas a slight increase in the creatinine baseline level was detected in all three animals. Autopsy results at the end of the study showed mild changes limited to the liver, kidney, and GI tract. Pharmacologic studies showed that the drug was cleared, fitting a two-compartment model with a mean t1/2 alpha of 7.1 min and a t1/2 beta of 87.8 h. These studies show that L-NDDP can safely be given at therapeutic doses to animals and that the dose-limiting toxic effects consists of myelosuppression in mice and a multiorgan hemorrhagic syndrome related to vascular injury in dogs.
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PMID:Preclinical toxicity and pharmacology of liposome-entrapped cis-bis-neodecanoato-trans-R,R-1,2-diaminocyclohexane platinum(II). 272 Aug 87


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