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)

A phase II study was undertaken to evaluate the clinical efficacy and safety of docetaxel in patients with malignant melanoma. Between April 1992 and February 1996, 37 patients with metastatic malignant melanoma and no prior chemotherapy were treated with docetaxel 100 mg m-2 administered intravenously over 1 hour every 21 days. Patients were premedicated prior to each course with dexamethasone and diphenhydramine. Toxicity and follow-up were provided. Objective responses were seen in two out of 35 patients evaluable for response, one complete response and one partial response. These two responses were of a duration of greater than two years. The most common toxicity was grade 4 neutropenia, which occurred in 92% of patients; 49% required hospitalization for an episode of neutropenic fever. Additional patients had reversible grade 3-4 toxicities including nausea, vomiting, diarrhea, stomatitis, arthralgias, myalgias, peripheral neuropathy and fatigue. Eighteen patients had hypersensitivity reactions, two were grade 3-4. Fluid retention, grade 1-3 was observed in seven patients. Alopecia occurred in most patients. Docetaxel has definite but low-level activity against malignant melanoma. Further investigation of this drug should be considered in multidrug combination programs.
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PMID:Phase II trial of docetaxel (Taxotere) in patients with metastatic melanoma previously untreated with cytotoxic chemotherapy. 901 74

Preliminary results of this ongoing phase II study of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) plus epirubicin administered as first-line treatment to women with metastatic breast cancer indicate encouraging response rates and no severe toxicity. Among the 57 patients admitted to this study, 52% had received prior adjuvant chemotherapy (85% with cyclophosphamide/methotrexate/5-fluorouracil), 46% had received radiotherapy, and 30% had received both forms of therapy; 63% of patients were postmenopausal, mainly with poorly differentiated tumors, and 80% presented with > or = 2 metastatic sites. Epirubicin 60 mg/m2 was administered intravenously as a 1-hour infusion followed by paclitaxel 175 mg/m2 infused over 3 hours. Standard premedication was given. Granulocyte colony-stimulating factor support was not used. Neutropenia was evident in 72% of cycles but was not severe. Instances of anemia and thrombocytopenia were rare. Alopecia was universal. All nonhematologic toxicity observed was mild or moderate (peripheral neuropathy, myalgia, nausea, vomiting World Health Organization toxicity grade < 2). At this time, 41 patients are currently evaluable for response, complete and partial remission are evident in seven and 21 patients, respectively. The overall response rate so far is 68%. An additional 12 patients show evidence of stable disease, and one has shown disease progression. Paclitaxel is considered a promising new drug in the adjuvant treatment of patients with metastatic breast cancer. Combining it with epirubicin allows safe administration with no evidence of severe cardiotoxicity. The incidence of adverse cardiac events was much lower than that observed with combinations of paclitaxel and doxorubicin.
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PMID:Preliminary results of a phase II study of epirubicin and paclitaxel as first-line treatment in patients with metastatic breast cancer. 907 34

Sixty patients with previously untreated non-small cell lung cancer of stages III and IV were treated with a 210 mg/m2 dose of paclitaxel by means of a 3-hour infusion. The objective response rate was 32% (95% confidence interval, 20-45%): 1 complete response and 18 partial responses. The median duration of response was 15 weeks, and the projected median survival duration of all patients was 30 weeks. Grade 3-4 neutropenia occurred in 73% of patients. Other grade 3-4 adverse events included anemia (5%), vomiting/nausea (8%), peripheral edema (2%), alopecia (7%), elevation of AST (2%), peripheral neuropathy (3%), allergic reaction (2%), arthralgia/myalgia (3%), and interstitial pneumonitis (3%). Paclitaxel administered at 210 mg/m2 by means of a 3-hour infusion every 3 weeks demonstrated a notable activity against previously untreated advanced non-small cell lung cancer, with a 32% major response rate. Major toxicity was neutropenia. Hypersensitivity, neurotoxicity, arthralgia/myalgia and cardiac toxicity were mild and easily managed.
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PMID:Phase II study of 3-hour infusion of paclitaxel in patients with previously untreated stage III and IV non-small cell lung cancer. West Japan Lung Cancer Group. 921 54

This phase I study was designed to determine the maximum tolerated dose of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) with standard doses of cisplatin and etoposide for patients with untreated, extensive-stage small cell lung cancer. Secondary objectives were to determine the toxicities, response rate, response duration, and overall survival in this cohort. Twenty-four patients were enrolled into four dose levels. All patients received a fixed dose of cisplatin at 80 mg/m2 intravenously (IV) on day 1. The first group received etoposide 50 mg/m2 IV on day 1 and 100 mg orally on days 2 and 3, while all subsequent groups received etoposide 80 mg/m2 IV on day 1 and 160 mg/m2 orally on days 2 and 3. The paclitaxel starting dose was 135 mg/m2 IV over 3 hours and escalated to 175 mg/m2 and 200 mg/m2. Cycles were repeated every 21 days for a maximum of six cycles. Granulocyte colony-stimulating factor was not given prophylactically, but was allowed in subsequent cycles according to American Society of Clinical Oncology guidelines. Nineteen patients were evaluable for toxicity and 18 patients were evaluable for response. Myelosuppression was the major toxicity, with grade 4 neutropenia occurring in 18 of 19 patients (95%), but febrile neutropenia was uncommon and developed in four of 19 patients (21%). Dose-limiting peripheral neuropathy was observed at a paclitaxel dose of 200 mg/m2. Grade 4 nausea/vomiting and diarrhea were also noted at this dose level. Four patients had complete responses (22%) and 13 patients had partial responses (72%). The overall response rate was 94%, with a median survival of 11 months and a 2-year survival rate of 19%. This three-drug combination of paclitaxel with cisplatin and etoposide is highly active with acceptable toxicity. Neurotoxicity was dose limiting at 200 mg/m2 paclitaxel. Neutropenia was frequent but was not associated with significant morbidity. The recommended doses for future clinical trials are paclitaxel 175 mg/m2 IV over 3 hours on day 1 with cisplatin 80 mg/m2 IV on day 1 and etoposide 80/160 mg/m2 IV on day 1 and orally on days 2 and 3. Growth factor support should be used according to American Society of Clinical Oncology guidelines.
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PMID:A phase I study of cisplatin, etoposide, and paclitaxel in small cell lung cancer. 933 Nov 40

The French Groupe des Investigateurs Nationaux pour l'Etude des Cancers Ovariens (GINECO) conducted a multicenter phase II study of carboplatin and paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) to evaluate the efficacy and side effects of this combination in pretreated advanced ovarian cancer. Patients with progressive ovarian carcinoma during or after platinum-based chemotherapy received paclitaxel 175 mg/m2 intravenously over 3 hours followed by intravenous carboplatin over 30 minutes every 4 weeks. The dose of carboplatin was calculated using a projected area under the concentration-time curve of 5 mg/mL x min. Of the 50 patients entered, 50 were evaluable for toxicity and 42 for response. There were eight complete and 10 partial responses, for an overall response rate of 43% (95% confidence interval, 28% to 56%). Overall response rates in platinum refractory patients and in those with early (> or = 3 and < 12 months) and late (> or = 12 months) relapse was 28%, 33%, and 71%, respectively. Median response duration, progression-free survival, and overall survivals were 8, 6, and 14 months, respectively. The most frequent and severe toxicity was myelosuppression. Grades 3 and 4 neutropenia occurred in 30% and 23% of cycles, and granulocyte colony-stimulating factor was administered in 6%. Only one case of neutropenic fever was observed. Grades 3 and 4 thrombocytopenia occurred in 3% and 1% of cycles, respectively. Alopecia and moderate nausea or vomiting were frequent. Transitory peripheral neuropathy was present in 45% of patients but was severe in only one patient. One early death was observed due to progressive disease and possibly to therapy. The combination of paclitaxel 175 mg/m2 as a 3-hour infusion and carboplatin dosed to an area under the concentration-time curve of 5 is an effective therapy in patients previously treated with platinum-based chemotherapy and may be administered safely to outpatients who relapse after one or two lines of chemotherapy.
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PMID:Efficacy and safety of the combination paclitaxel/carboplatin in patients with previously treated advanced ovarian carcinoma: a multicenter French Groupe des Investigateurs Nationaux pour l'Etude des Cancers Ovariens phase II study. 934 19

The aim of this trial was to identify the maximum tolerated dose of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) administered via a 3-hour infusion day 1, together with cisplatin 20 mg/m2/d days 1 to 3 and 5-fluorouracil 200 mg/m2/d bolus days 1 to 3 every 21 days. The prophylactic administration of colony-stimulating factors was not allowed. Twenty-three patients with relapsed and/or metastatic squamous cell carcinoma of the head and neck previously treated with surgery and/or radiotherapy were accrued. None had received chemotherapy previously. No grade 3/4 hematologic toxicity at nadir or other limiting toxicities were recorded with paclitaxel at 100 to 135 mg/m2 (six patients, 26 courses). Seven patients (six evaluable, 22 courses) were treated with 160 mg/m2. Grade 4 neutropenia at nadir with fever lasting 3 days was observed in one patient. Nonhematologic toxicities, including temporary peripheral neuropathy, asthenia, myalgias, vomiting, and mucositis were generally mild. Three patients were treated with 180 mg/m2 (eight courses). Grade 4 neutropenia at nadir was recorded in all patients and was febrile in two. Seven patients (six evaluable, 23 courses) were treated with paclitaxel 160 mg/m2, cisplatin 25 mg/m2/d, and 5-fluorouracil 250 mg/m2/d. Grade 4 febrile neutropenia at nadir was recorded in one patient. One episode of grade 4 mucositis and two episodes of grade 3 diarrhea were also recorded. Overall, eight responses (38%) were observed. In conclusion, the combination of paclitaxel 160 mg/m2, cisplatin 25 mg/m2/d, and 5-fluorouracil 250 mg/m2/d for 3 consecutive days can be administered safely without growth factor support. This regimen merits further investigation in a phase II trial.
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PMID:Chemotherapy for relapsed head and neck cancer: paclitaxel, cisplatin, and 5-fluorouracil in chemotherapy-naive patients. A dose-finding study. 942 66

Three hepatic porphyrias--acute intermittent porphyria, hereditary coproporphyria and variegate porphyria--are characterized by episodic acute attacks that consist of various neuro-psychiatric symptoms and signs, such as abdominal pain, vomiting, constipation, hypertension and tachycardia associated with increased excretion of porphyrins and porphyrin precursors. Peripheral neuropathy is manifested as pain in the extremities, and it may progress to a severe motor neuropathy. Measurement of porphobilinogen in the urine gives a prompt diagnosis during acute attacks. Attacks are often induced by precipitating factors such as drugs, alcohol, infection, fasting or changes in sex-hormone balance, and they should be eliminated when a patient is treated during an attack. Heme, the end biosynthetic product, is the most effective therapy for restoration of porphyrin biosynthesis to normal, and it is usually infused at 3 mg/kg daily for 4 days. Adequate calories are necessary and parenteral nutrition with carbohydrates may be necessary. Attacks may also require therapy for hypertension, pain and epileptic seizures. Strict avoidance of all precipitating factors may not be necessary in the asymptomatic phase.
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PMID:Management of the acute porphyrias. 963 23

Two siblings (one man, one woman), presenting with diarrhea, severe weight loss peripheral neuropathy, ophthalmoparesis, asymptomatic leukoencephalopathy were diagnosed as a new cases of Mitochondrial Neuro Gastro Intestinal Encephalomyopathy syndrome (MNGIE). Hirano (1994) defined four criteria for the diagnostic: peripheral neuropathy, ophthalmoparesis, gastro intestinal dysmotility, muscle biopsy with histologic features of mitochondrial myopathy (ragged-red fibers, muscle fibers with increased succinate deshydrogenase stain or ultra structurally abnormal mitochondria). In a review of the literature, we found 31 cases with MNGIE. With our two cases, we study this group of 33 patients. First symptoms begin about 13.5 years with a median of 10 years and extremes for 1 to 32 years. The first signs are gastro intestinal symptoms (recurrent nausea, vomiting or diarrhea with intestinal dysmotility) in 22 cases, an ophthalmoparesia in 4 cases, intestinal and ocular signs in 1 case, gait ataxia or peripheral neuropathy in 3 cases, hearing loss in 1 case, gait ataxia or peripheral neuropathy in 3 cases, hearing loss in 1 case. During the evolution, besides the cardinal signs, the following features have been observed with a variable frequency: hearing loss, short stature, facial palsy, dysphonia, dysarthria, sweating, orthostatic hypotension, bladder dysfunction, hepatomegalia, The laboratory features are: abnormal Nerve Condition Studies/EMG compatible with a sensory motor neuropathy, lactic acidosis, mitochondrial respiratory chain defect (essentially complex IV deficiency, complex I deficiency or multiple complex defect), MRI leukodystrophy, elevated CSF protein, heart block, ragged-red fibers or increased SDH stain. The prognosis is poor, due to a severe weight loss bordering on cachexia 13 patients died with a mean age of 28.5 years (median 24 years, extreme 3 years to 51 years). The prognosis seems to be worsened by a young age of onset. The 33 patients belong to 19 families with 7 cases of consanguinity. 25 patients had a brother, a sister or a cousin affected. The study of these families is compatible with an autosomic recessive transmission, suggesting a pathology of the nuclear genomi, probably impliying the control of the mitochondrial DNA replication. In fact, in 13 cases, a study of the mt DNA was realized: multiple deletions were founded in 6 cases, multiples mutations in one case, unique mutation in 1 case. In 5 cases ther was no evidence of abnormality. These precise etiology and pathophysiologic significance of the mt DNA deletions, and the heterogeneity of the modifications of the mt DNA remain unknown. However, the possibility of various phenotypes for a same genotype or inversely is known in mitochondriopathies.
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PMID:[MNGIE syndrome in 2 siblings]. 968 18

A 14-year-old girl with the mitochondrial neurogastrointestinal encephalopathy syndrome had an 8-year history of intestinal pseudoobstruction with abdominal pain, persistent vomiting, gastric and duodenal dilatation, and duodenal diverticulosis. The child appeared chronically malnourished and had severe growth failure. Multisystem involvement was evident with the presence of ptosis, external ophthalmoplegia, muscle wasting, peripheral neuropathy, and diffuse white matter disease seen on magnetic resonance imaging. Lactic acidosis and increased cerebrospinal fluid protein were observed. Mitochondrial enzyme analysis of fresh-frozen skeletal muscle revealed a respiratory chain defect. Molecular genetic studies showed multiple mitochondrial DNA deletions. Pathologic findings in the intestine included atrophy of the external layer of the muscularis propria and an increased number of abnormal-appearing mitochondria in ganglion and smooth-muscle cells. Microvesicular steatosis was observed in liver, skeletal, and gastrointestinal smooth muscle, and Schwann cells of peripheral nerve. Brightly eosinophilic inclusions in the cytoplasm of gastrointestinal ganglion cells were visible by light microscopy, which were confirmed to be megamitochondria by ultrastructural studies. This is the first report of abnormal mitochondria observed in intestinal ganglion and smooth-muscle cells in this syndrome.
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PMID:Mitochondrial neurogastrointestinal encephalomyopathy: diagnosis by rectal biopsy. 973 48

Forty-eight patients with advanced head and neck tumours were treated with irradiation and concomitant chemotherapy with cisplatin, vindesine and hyaluronidase. The disease-free survival rate at 5 years was 47%. The toxic effects were mucositis (48 patients), nausea (25 patients, vomiting in six patients), bone marrow depression (15 patients) and peripheral neuropathy (14 patients). The results warrant a randomized trial.
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PMID:Hyaluronidase as additive to induction chemotherapy in advanced squamous cell carcinoma of the head and neck. 983 26


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