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The measurement of urinary ifosfamide, isophosphoramide mustard, dechloroethyl ifosfamide and carboxyifosfamide using high-performance thin-layer chromatography with photographic densitometry (TLC-PD) is described. This technique was also used to demonstrate the large inter-individual variation in the ifosfamide metabolic profile of patients receiving the(More)
The pharmacokinetics of intravenous ifosfamide were determined in 16 patients with carcinoma of the bronchus. In all 25% (4) of these patients were obese (i.e. >20% over their ideal body weight). The terminal elimination half-life (t1/2 β) was found to be higher in the obese group than in the control group (6.36 h, range 5.77–7.45 h) vs 4.95 h, range(More)
PURPOSE Studies have reported an association between hospital volume and survival for non-small-cell lung cancer (NSCLC). We explored this association in England, accounting for case mix and propensity to resect. METHODS We analyzed data on 134,293 patients with NSCLC diagnosed in England between 2004 and 2008, of whom 12,862 (9.6%) underwent surgical(More)
Purpose: This study was designed to determine individual variation in the metabolism of ifosfamide (IF) and any influence this may have on the degree of DNA damage produced in both peripheral blood lymphocytes (PBL) and in tumour tissue. Methods: The pharmacokinetics and metabolism of IF and also of doxorubicin (DOX) were determined in patients receiving(More)
BACKGROUND Breast cancer patients with four or more positive axillary lymph nodes who are treated with conventional adjuvant therapy have a poor prognosis. In uncontrolled studies, high-dose chemotherapy produced much better results than conventional therapy. We compared the benefits of a single cycle of high-dose chemotherapy and the benefits of(More)
beta-tubulin is the target of various antitubulin agents used in the treatment of cancer. After beta tubulin was shown to confer resistance to antitubulin agents in established cell lines, several studies have investigated the DNA sequence of this compound in clinical samples. However, these findings are highly controversial, since sequencing experiments(More)
The pharmacokinetics and pharmacodynamics of prolonged oral etoposide chemotherapy were investigated in 15 women with metastatic breast cancer who received oral etoposide 100 mg as a single daily dose for up to 15 days. There was considerable interpatient variability in the day 1 pharmacokinetic parameters: area under the plasma concentration time curve(More)
The aim of this phase I study was to determine the maximum tolerated dose of a 3-h infusion of paclitaxel, combined with carboplatin at a fixed AUC of 7 mg ml-1 min every 4 weeks for up to six cycles and to evaluate any possible pharmacokinetic interaction. Twelve chemonaive patients with ovarian cancer were treated with paclitaxel followed by a 30-min(More)
Dose fractionation is known to reduce the toxicity of ifosfamide and also results in an increased production of alkylating metabolites. Administration by slow infusion using the convenience of ambulatory pumps is therefore of interest. We used HPLC to investigate the stability of ifosfamide in aqueous solution (either alone, solution A, or mixed with mesna,(More)
For the first time in a clinical study oral Ifosfamide was used: 65 elderly or unfit patients with small cell lung cancer (SCLC) were treated as outpatients with fractionated oral Ifosfamide and Etoposide. Forty patients (62%) had extensive stage (ED) disease. The median age of the patients was 66 years. In the 60 patients evaluable for response the(More)