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 effects of synthetic salmon CT, administered subcutaneously and intermittently (1 MRC U/kg/day for 15 days/month over 6 months) were investigated in 15 uremic patients on regular dialysis treatment (RDT), all presenting various degrees of osteodystrophy. Clinically, osteoarticular pain disappeared in 8 out of 10 cases; 1 patient with rib fractures had a rapid calcification of the bone fracture repair tissue. No significant changes were found in serum calcium and PTH levels. Phosphotemia showed a significant decrease within the first 20 days. The varying individual hypophosphatemic response proved to be related to the initial level of phosphatemia. The alkaline phosphatase, when increased, showed a decrease to the normal range. A significant decrease in osteoclastic hyperactivity (active resorption surface, osteoclast index) and a slight increase in osteoblastic pool (active osteoid surface) were documented. No change was noted when osteomalacia predominated. Side effects included: anorexia, nausea, vomiting, face flushing. Our data suggest that salmon CT may be usefully employed in chronic uremic patients on RDT, when secondary hyperparathyroidism predominates.
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PMID:Effect of calcitonin on bone lesions in chronic dialysis patients. 49 16

High dose melphalan (HDM, 140 mg/m2 i.v.) has been evaluated in 58 patients under 63 years with multiple myeloma. Among previously untreated patients 11/41 (27%) entered a complete remission (CR: no measurable myeloma protein and a normal bone marrow) and 21 (51%) entered a partial remission (more than 50% reduction in myeloma protein and improvement in all other features). Median duration of remission is 19 months. Two patients who had responded to previous conventional treatment entered CR after HDM. Among 15 patients who had failed on previous chemotherapy the response rate was 66% including two CRs. However, in this group all patients have relapsed within 1 year. Profound myelosuppression, moderate nausea, vomiting, mucositis and diarrhoea with reversible alopecia occurred in all patients. There were 10 deaths within 2 months of treatment mainly due to sepsis and haemorrhage. In a subsequent study, high dose methyl prednisolone (1 g/m2 daily for 5 d) has been added to HDM. Response rates are similar with 6/22 (27%) CR, 13/22 (59%) PR and 2/22 NR but there was only one early death, reflecting improvements in medical management. The high CR rate is an encouraging feature of this approach which is now to be the basis of a prospective trial sponsored by the Medical Research Council in which HDM, with and without steroids, is compared to the best available conventional therapy (the MRC VI Myelomatosis trial).
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PMID:Multiple myeloma treated with high dose intravenous melphalan. 359 57

The serotonin (5HT3) antagonist ondansetron was compared in a randomised study with metoclopramide and dexamethasone for the prevention of chemotherapy induced emesis. Thirty children aged 1-15 years with acute lymphoblastic leukaemia received 'intensification modules' according to the MRC United Kingdom acute lymphoblastic leukaemia regimen UKALL XI. This contains the moderately emetogenic drugs daunorubicin, etoposide, and cytarabine. Fifteen children received an intravenous loading dose of ondansetron followed by intravenous or oral doses 12 hourly for five days. Fifteen children received intravenous metoclopramide every six hours for three days with a loading dose of dexamethasone, repeated every eight hours for three days intravenously or orally. Efficacy was assessed by a diary card documenting the incidence of nausea, retching, or vomiting. In the 24 hour period after starting chemotherapy, ondansetron was more effective, with a complete or major response rate of 93%, compared with 33% using metoclopramide/dexamethasone.
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PMID:Randomised comparison of ondansetron and metoclopramide plus dexamethasone for chemotherapy induced emesis. 749 64

A total of 458 eligible patients, from 21 centres, with microscopically confirmed SCLC were allocated at random to three chemotherapy regimens, each given at 3-week intervals. In two regimens, etoposide, cyclophosphamide, methotrexate and vincristine were given for a total of either three courses (ECMV3) or six courses (ECMV6). In the third regimen, etoposide and ifosfamide were given for six courses (E16). Patients with limited disease also received radiotherapy to the primary site after the third course of chemotherapy in all three groups. As reported by clinicians, 59% of the ECMV3, 67% of the ECMV6 and 63% of the EI6 patients experienced moderate or severe adverse reactions to their chemotherapy. The major symptoms of disease, cough, haemoptysis, chest pain, anorexia, and dysphagia, were palliated in 63% or more of patients and the median duration of palliation was 63% or more of survival, the results being similar in the three groups. Among patients with poor overall condition, physical activity and breathlessness on admission, the proportions who improved were higher in the EI6 group but the differences were small. In all three groups, levels of anxiety fell substantially during treatment. Levels of depression were lower and showed little change. As assessed by patients using a daily diary card, the patterns of nausea, vomiting, activity and mood, associated with courses of chemotherapy were very similar in the three groups. In the EI6 group there was less dysphagia and better overall condition between courses, but these advantages need to be weighed against the inconvenience of the 24-h infusions required, compared with the 30-min infusions of the other two regimens. As reported in the companion paper (MRC Lung Cancer Working Party, 1993a) there was no statistically significant survival advantage to any of the three regimens, although the results do not exclude the possibility of a minor survival advantage with the two six-course regimens. In conclusion, there was no major clinical gain from continuing chemotherapy beyond three courses or from using the ifosfamide regimen.
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PMID:A randomised trial of three or six courses of etoposide cyclophosphamide methotrexate and vincristine or six courses of etoposide and ifosfamide in small cell lung cancer (SCLC). II: Quality of life. Medical Research Council Lung Cancer Working Party. 750 4

The purpose of this pilot study was to evaluate the acute gastrointestinal morbidity of adjuvant radiotherapy (RT) for Stage I seminoma of the testis. Ten Stage I patients receiving para-aortic and ipsilateral pelvic nodal (dog-leg) RT provided a toxicity baseline (group A). Twenty Stage I patients, randomized to dog-leg RT or para-aortic RT (10 per group) were further randomized to received prophylactic ondansetron or expectant therapy with metoclopramide (group B). Daily patient-completed questionnaires evaluated acute toxicity. In group A (n = 10), nausea, vomiting, diarrhoea and abdominal discomfort were experienced in 90%, 80%, 70% and 90% respectively. Antiemetic and antidiarrhoeal agents were required in 70% and 10% respectively, with good response. For group B (n = 20), the overall incidences of nausea, vomiting diarrhoea and abdominal discomfort were 80%, 45%, 60% and 80% respectively. The ondansetron group experienced less nausea (P = 0.02) and less vomiting (P = 0.06). Both reduced field size and ondansetron groups appeared to have less diarrhoea (P = 0.06). The use of antiemetics in the expectant therapy groups resulted in at least a two-level reduction of toxicity grade in 86% of patients. A high incidence of lethargy, anorexia and headaches was noted for all groups. The incidence of headaches was not increased with ondansetron. Dog-leg RT for Stage I seminomas is associated with readily demonstrable gastrointestinal tract (GIT) toxicity. The number of patients in this study is too small to produce definitive results, but there appears to be reduced GIT toxicity with prophylactic antiemetics. The effect of reduced RT fields has been assessed further in the MRC randomized trial of field sizes (TE10).
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PMID:The effect of antiemetics and reduced radiation fields on acute gastrointestinal morbidity of adjuvant radiotherapy in stage I seminoma of the testis: a randomized pilot study. 931 92

Epirubicin, cisplatin and continuous 5-fluorouracil (5-FU) infusion (ECF) has been reported to result in high clinical response rates in advanced gastro-oesophageal adenocarcinoma and is currently the 'gold standard' chemotherapy regimen for this tumour site. Despite this, its role as preoperative (neoadjuvant) treatment is unproven and therefore remains under investigation. We report our experience using ECF (intravenous epirubicin 50 mg/m2 and cisplatin 60 mg/m2 every 3 weeks, with continuous infusion of 5-FU 200 mg/m2 per day) as preoperative treatment in locally advanced adenocarcinoma of the lower oesophagus, gastro-oesophageal junction and stomach. Of the 23 patients treated (median age 54 years), 19 had potentially resectable disease, four were unresectable and seven had radiological evidence of lymph node involvement. A median of four cycles of ECF was delivered (range 1-6). Ten of 12 patients (83%) with dysphagia reported improvement of symptoms. Clinical disease progression occurred in six patients (26%) during chemotherapy. WHO grade 3 or 4 toxicity occurred in six patients (26%): four haematological, one mucositis, one vomiting. Seventeen patients (74%) proceeded to surgery; 14 (61%) were resected and three were unresectable. There were two (12%) postoperative deaths from respiratory failure. Major pathological response was seen in three patients (13%): one pathological complete response, two microscopic residual disease. Two patients had Stage II (T2N(0-1)) disease and nine were Stage III (T(3-4)N(0-1)). None of the patients with initially unresectable disease was rendered resectable. After a median follow-up interval of 33 months (range 26-53), the overall median survival was 12 months and 2-year survival was 30%. All patients who were initially unresectable or had radiological evidence of lymph node involvement have died. Therefore, despite good symptomatic response rates, ECF chemotherapy given in the preoperative setting did not appear to improve the outcome of patients with unresectable or radiologically lymph node-positive gastro-oesophageal adenocarcinoma. The role of ECF chemotherapy in resectable tumours is unclear and is currently under investigation in the randomized MRC Adjuvant Gastric Infusional Chemotherapy (MAGIC) study.
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PMID:Preoperative ECF chemotherapy in gastro-oesophageal adenocarcinoma. 1094 36

The standard de Gramont (dG) regimen of fortnightly leucovorin, bolus fluorouracil and 22-h infusion of fluorouracil, d1+2, and the same regimen plus oxaliplatin, are effective but also cumbersome. We therefore present simplified 'Modified de Gramont' (MdG) regimens. Forty-six advanced gastrointestinal cancer patients entered a dose-exploring study of MdG, including an expanded cohort of colorectal cancer patients at optimum dose. Treatment (fortnightly) comprised: 2-h i.v.i. leucovorin (350 mg d,l-LV or 175 mg l-LV, not adjusted for patient surface area); bolus fluorouracil (400 mg m(-2)), then ambulatory 46-h fluorouracil infusion (2000-3600 mg m(-2), cohort escalation). Subsequently, 62 colorectal patients (25 unpretreated; 37 fluorouracil-resistant) received MdG plus oxaliplatin (OxMdG) 85 mg m(-2). Fluorouracil pharmacokinetics during MdG were compared with dG. The optimum fluorouracil doses for MdG alone were determined as 400 mg m(-2) bolus + 2800 mg m(-2) 46-h infusion. A lower dose of 400 mg m(-2) bolus + 2400 mg m(-2) infusion which, like dG produces minimal toxicity, was chosen for the OxMdG combination. Fluorouracil exposure (AUC(0-48 h)) at this lower dose is equivalent to dG. With OxMdG, grade 3-4 toxicity was rare (neutropenia 2.8% cycles; vomiting or diarrhoea <1% cycles), but despite this there were two infection-associated deaths. Oxaliplatin was omitted for cumulative neurotoxicity in 17 out of 62 patients. Objective responses in colorectal cancer patients were: 1st-line MdG (22 assessable): PR=36%, NC=32%, PD=32%. 1st-line OxMdG (24 assessable): CR/PR=72%; NC=20%; PD=8%; 2nd line OxMdG (34 assessable): PR=12%; NC=38%; PD=50%. MdG and OxMdG are convenient and well-tolerated. OxMdG was particularly active as 1st-line treatment of advanced colorectal cancer. Both regimens are being further evaluated in the current UK MRC phase III trial.
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PMID:A 'modified de Gramont' regimen of fluorouracil, alone and with oxaliplatin, for advanced colorectal cancer. 1217 75

We present the preliminary toxicity data from the MRC COIN trial, a phase III randomised controlled trial of first-line therapy in advanced colorectal cancer, with particular reference to the addition of cetuximab to an oxaliplatin-fluoropyrimidine combination. A total of 804 patients were randomised between March 2005 and July 2006 from 78 centres throughout the United Kingdom. Patients were allocated to oxaliplatin plus fluoropyrimidine chemotherapy with or without the addition of weekly cetuximab. The choice of fluoropyrimidine (either 5-fluorouracil (5FU) or capecitabine) was decided by the treating physician and patient before randomisation. Toxicity data were collected from all patients. Two hundred and three patients received 5FU plus oxaliplatin (OxMdG, 25%), 333 oxaliplatin+capecitabine (Xelox, 41%), 102 received OxMdG+cetuximab (OxMdG+C, 13%) and 166 Xelox+cetuximab (21%). Percent grade 3/4 toxicities included diarrhoea 6, 15, 13 and 25%, nausea/vomiting 3, 7, 7 and 14% for OxMdG, Xelox, OxMdG+C and Xelox+C, respectively. Sixty-day all-cause mortality was 6, 5, 5 and 7%. Statistically significant differences were evident for patients receiving Xelox+cetuximab vs Xelox alone: diarrhoea relative risk (RR) 1.69 (1.17, 2.43, P=0.005) and nausea/vomiting RR 2.01 (1.16, 3.47, P=0.012). The excess toxicity observed in the oxaliplatin-, capecitabine-, cetuximab-treated patients led the trial management group to conclude that a capecitabine dose adjustment was required to maintain safety levels when using this regimen.
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PMID:Toxicity associated with combination oxaliplatin plus fluoropyrimidine with or without cetuximab in the MRC COIN trial experience. 1916 96