Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Retrospective analysis of detailed patient and tumour factors associated with a complete response to combination inductive chemotherapy with CDDP-5FU (96 or 120 hour continuous infusion) was performed using data from 147 patients with a previously untreated squamous cell carcinoma of the oral cavity, oropharynx or pharyngo-larynx following completion of two (29 patients) or three (118 patients) cycles. Adverse reactions to chemotherapy were documented for all 164 patients included in the study. Eight drug-related deaths occurred due to: acute myocardial infarction (five patients), peptic ulcer disease (two patients) and severe neutropenia with sepsis (one patient). Severe non-lethal complications included marrow depletion (14 patients), peptic ulcer (two patients), thrombophlebitis (seven patients), angina pectoris (two patients), stroke (one patient), pulmonary oedema (one patient) and convulsions (one patient). Six patients refused further treatment because of untoward side effects and tumoral progression was observed in three cases. Separate response rates for the primary site and nodes were determined and analysis of respective predictive factors of response was performed. Complete response was obtained in 31 per cent at the primary site versus 18 per cent for the nodes (p < 0.05). The combined (primary site + nodes) overall complete response rate was 22 per cent. Among 11 factors studied (age, sex, performance status, primary site, tumour differentiation, initial resectability, 5FU dosage per cycle, number of cycles, T, N and TN stages), only performance status, N stage, resectability and number of cycles were associated with a combined complete response. Multivariate analysis showed performance status, N stage, TN stage and resectability to be significant predictive factors of a combined complete response.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Predictive factors of a complete response to and adverse effects of a CDDP-5FU combination as primary therapy for head and neck squamous carcinomas. 826 92

A prospective phase II study was conducted to determine the response, toxicity and survival rate of lung cancer patients treated with combination paclitaxel and carboplatin in stage IIIB and IV NSCLC. Eligible patients required measurable and/or evaluable diseases; performance status (ECOG) 0-2; no previous chemotherapy; adequate hepatic, renal and bone marrow function. Paclitaxel was administered at a dose of 200 mg/m2, 3 h infusion, followed by carboplatin at an AUC of 6. Treatment was repeated every 3 weeks for six courses. G-CSF 5 microgram/kg was subcutaneously injected during subsequent courses if there was grade 3-4 leucopenia or granulocytopenia in the previous course. From April 1996 through July 1997, 53 patients were enrolled; all are assessable for toxicity and response. The median age was 56 years (range, 20-77 years). Sixty four percent were male, 64% had adenocarcinoma and 62% had stage IV disease. Two hundred and seventy two courses were administered; 36 patients (68%) completed all six cycles. Two patients achieved a complete response (4%) and 27 patients achieved a partial response (51%), for an overall response rate of 55%. Sixteen patients had stable disease (30%) and 8 patients had progressive disease (15%). The median progression free survival time for all patients, stage IIIB and stage IV patients was 28 weeks (range, 18-37 weeks), 31 weeks (range 21-41 weeks) and 22 weeks (range 16-29 weeks), respectively. The median survival time and 1 year survival rate for all patients was 55 weeks (range, 51-59 weeks) and 55%, respectively. Stage IIIB patients had better median survival time and 1-year survival rate than stage IV patients (75 vs. 46 weeks, P = 0.007; 80% vs. 42%, P = 0.003). Grade 3 and 4 granulocytopenia, anemia and thrombocytopenia were observed in 25, 3, and 1%, respectively, of the 272 courses administered. G-CSF was required in 28% of the 272 courses. There were four episodes of febrile neutropenia (1.5%), three episodes of angina pectoris (1%) and one episode of anaphylaxis (0.4%). Other common toxicities, generally mild, included myalgia, arthralgia, peripheral neuropathy and asthenia. Most toxicities showed cumulative effect. Paclitaxel plus carboplatin is a moderately active regimen in advanced NSCLC. Toxicities of this regimen are well tolerated.
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PMID:Phase II study of paclitaxel and carboplatin for advanced non-small-cell lung cancer. 1059 28

(1) Chemotherapy does not appear to prolong the survival of patients with inoperable pleural mesothelioma, and the tumour response rate barely exceeds 20%. A combination of cisplatin + doxorubicin seems to provide the best response rates. (2) In a trial of second-line docetaxel therapy in patients with non small cell lung cancer, survival was extended by about 3 months compared with palliative care (7.5 versus 4.6 months). (3) Pemetrexed, an antifolate closely related to methotrexate and raltitrexed, has been authorized for use for both conditions. (4) In a randomised single-blind trial involving 456 patients with previously untreated pleural mesothelioma, survival was prolonged by about 3 months by a cisplatin + pemetrexed combination in comparison with cisplatin + placebo (12.1 versus 9.3 months). The respective tumour response rates were 41.3% and 16.7%. This is the only available comparative trial of pemetrexed in patients with mesothelioma. A more appropriate comparator would have been a cisplatin-based regimen such as cisplatin + doxorubicin. (5) A "non inferiority" trial of second-line treatment in 571 patients with locally advanced or metastatic non small cell lung cancer showed no significant difference in median survival time with pemetrexed versus docetaxel (about 8 months with both treatments). However, this trial does not rule out the possibility that pemetrexed is less effective than docetaxel. (6) Supplementation with folic acid and vitamin B12 reduces haematological and gastrointestinal complications associated with the antifolate activity of pemetrexed. (7) Despite this supplementation, more than 15% of patients in the mesothelioma trial developed severe neutropenia, leukopenia or fatigue during cisplatin + pemetrexed therapy. Pemetrexed aggravates the nausea and vomiting provoked by cisplatin, a drug that is highly emetic. (8) The adverse effects of pemetrexed were similar to those of docetaxel in the trial comparing the two drugs. However, neutropenia (5% versus 40%) and febrile neutropenia (2% versus 13%) occurred less frequently with pemetrexed. (9) Patients receiving pemetrexed must be monitored closely for some rare but potentially severe adverse effects; they include angina, myocardial infarction and stroke, liver damage, and bullous skin rash. (10) According to the summary of product characteristics (SPC), pemetrexed therapy must be administered in combination with folic acid and vitamin B12 supplementation in order to reduce haematological toxicity, and also with corticosteroid therapy to reduce the risk of serious skin reactions. (11) In practice, given the absence of a better alternative, and pending the results of a second trial, the cisplatin + pemetrexed combination can be used as a first-line regimen for patients with pleural mesothelioma. However, pemetrexed cannot replace docetaxel in second-line treatment of non small cell lung cancer.
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PMID:Pemetrexed: new drug. Pleural mesothelioma: a first encouraging trial. 1640 Jul 41

R1 The diagnosis of Graves' disease in children is based on detecting a suppression of serum TSH concentrations and the presence of anti-TSH receptor antibodies. 1/+++. R2 Thyroid ultrasound is unnecessary for diagnosis, but can be useful for assessing the size and homogeneity of the goiter. 2/+. R3. Thyroid scintigraphy is not required for the diagnosis of Graves' disease. 1/+++. R4. The measurement of T4L and T3L levels is not necessary for the diagnosis of Graves' disease in children but can be useful for the management and assessment of prognosis. 1/++. R5. In the absence of TSH receptor autoantibodies, the possibility of genetically inherited hyperthyroidism must be considered. 1/++. R6. Drug therapy is the primary line of treatment for children and consists of imidazole, carbimazole or thiamazole, with an initial dosage of 0.4 to 0.8mg/kg/day (0.3 to 0.6mg/kg/day for thiamazole) depending on the initial severity, up to maximum of 30mg. 1/++. R7. Propylthiouracil is contraindicated for children with Grave's disease. 1/+++. R8. Before starting treatment, it may be useful to perform a CBC in order to assess the degree of neutropenia caused by hyperthyroidism. It is not necessary to perform systematic CBCs during follow-up. 2/+. R9. An emergency CBC should be performed if symptoms include fever or angina. If neutrophil counts are <1000/mm3, synthetic antithyroid therapy should be discontinued or decreased and may be permanently contraindicated in severe (<500) and persistent neutropenia. Otherwise treatment may be resumed. 1/++. R10. Transaminases levels should be measured before initiating treatment. Systematic monitoring of liver function is not consensually validated. 2/+. R11. In cases of jaundice, digestive disorders or pruritus, measuring liver enzymes (AST, ALT), total and conjugated bilirubin and alkaline phosphatases is indicated. 1/++. R12. Patients and parents should be informed of the possible side effects of antithyroid agents. 1/+. R13. Therapeutic education of parents and children is important in ensuring the best possible treatment compliance. 2/++. R14. Given the specificities involved in the treatment of Graves' disease in children, medical care should be provided by a specialist accustomed to treating endocrinopathies in pediatric patients. 2/+. R15. Depending on patient age, the severity of the disease at diagnosis and the persistence of anti-TSH receptor antibodies, the initial course of treatment must take place over an extended period of 3 to 6 years. R16.The anticipated success rates of medical treatment (50% of patients in remission following several years of treatment) should be explained to the family and the child. The possibility that radical treatment may be required in case of failure or intolerance of medical treatment should also be discussed. 1/++. R17.In females with Graves' disease, it is important to explain that they must undergo an assessment by an endocrinologist before planning future pregnancies, from the start of pregnancy and during the course of pregnancy. This is true in all female patients, even those in remission after medical treatment, or those who have undergone radical treatment. R18.Indications for a radical treatment can arise in cases of: 1/+: contraindication to antithyroid agents; poorly controlled hyperthyroidism due to lack of compliance; relapse despite prolonged medical treatment; a request made by the family and child for personal reasons. R19.Surgery is the radical method of treatment used in children under 5 years of age, or in cases of very large, nodular, or compressive goiters. 2/++. R20. The surgeon's experience in dealing with thyroidectomies in children is likely to be the most significant determining factor in limiting the morbidity of the procedure (alongside any collaboration between a pediatric surgeon and an adult surgeon). 1/++. R21 When radical treatment is indicated, I-131 treatment may be discussed after 5 years (but more often after puberty), if the goiter is not too large. Experience from monitoring Graves' disease in North American children is reassuring. 1/++.
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PMID:Graves' disease in children. 3018 Sep 72