British journal of cancer
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British journal of cancer · Oct 1999
Genetic polymorphisms of N-acetyltransferase 1 and 2 and risk of cigarette smoking-related bladder cancer.
Aromatic amines from cigarette smoking or occupational exposure, recognized risk factors for bladder cancer, are metabolized by N-acetyltransferases (NAT). This study examined the association of (NAT) 1 and 2 genotypes with the risk of smoking-related bladder cancer. A total of 74 pathologically confirmed bladder cancer patients and 184 controls were serially recruited from the National Taiwan University Hospital. ⋯ There was a significant dose-response relationship between the risk of bladder cancer and the quantity and duration of cigarette smoking. The biological gradients were significant among subjects carrying NAT1*10 allele or NAT2 slow acetylators, but not among NAT2 rapid acetylators without NAT1*10 allele. The results are consistent with the hypothesis that NAT1 and NAT2 might modulate the susceptibility to bladder cancer associated with cigarette smoking.
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This study investigated changes and the time course of these changes in renal function in children following treatment with carboplatin, and identified risk factors for nephrotoxicity. Glomerular and proximal renal tubular function were investigated before and up to 2 years after treatment in 23 children who received carboplatin. The main findings were reduced glomerular filtration rate (GFR), and increased renal tubular loss of magnesium, manifested by a low serum magnesium (S Mg). ⋯ CD, AUC and DI of carboplatin were not related to GFR, nor change in GFR, after treatment. High CDs of carboplatin may be associated with evidence of renal damage qualitatively similar to but less severe than that caused by cisplatin. GFR and SMg should be carefully monitored when high CDs of carboplatin are used, or if carboplatin is combined with other nephrotoxic chemotherapy.
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British journal of cancer · Sep 1999
Cremophor EL causes (pseudo-) non-linear pharmacokinetics of paclitaxel in patients.
The non-linear plasma pharmacokinetics of paclitaxel in patients has been well established, however, the exact underlying mechanism remains to be elucidated. We have previously shown that the non-linear plasma pharmacokinetics of paclitaxel in mice results from Cremophor EL. To investigate whether Cremophor EL also plays a role in the non-linear pharmacokinetics of paclitaxel in patients, we have established its pharmacokinetics in patients receiving paclitaxel by 3-, 24- or 96-h intravenous infusion. ⋯ Despite its relatively low molecular weight, no Cremophor EL was found in the ultrafiltrate fraction. Our results strongly suggest that entrapment of paclitaxel in plasma by Cremophor EL, probably by inclusion in micelles, is the cause of the apparent nonlinear plasma pharmacokinetics of paclitaxel. This mechanism of a (pseudo-)non-linearity contrasts previous postulations about saturable distribution and elimination kinetics and means that we must re-evaluate previous assumptions on pharmacokinetics-pharmacodynamics relationships.
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British journal of cancer · Aug 1999
Multicenter Study Clinical TrialConcurrent conventionally factionated radiotherapy and weekly docetaxel in the treatment of stage IIIb non-small-cell lung carcinoma.
Docetaxel has shown remarkable radiosensitizing in vitro properties. In a previous phase I/II dose escalation study in non-small-cell lung cancer (NSCLC) we observed a high response rate after concomitant boost radiotherapy and weekly docetaxel. The maximum tolerated dose was 30 mg m(-2) week(-1). ⋯ The overall survival and the local progression-free survival at 1 year was 48% and 60% respectively. We conclude that docetaxel combination with radiotherapy is a promising approach for the management of locally advanced NSCLC that results in high CR rate. Further trials with docetaxel-based radiochemotherapy should integrate accelerated radiotherapy together with cytoprotection.
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British journal of cancer · Aug 1999
Clinical TrialLeucocyte nadir as a marker for chemotherapy efficacy in node-positive breast cancer treated with adjuvant CMF.
The purpose of this study was to examine the association between the leucocyte nadir and prognosis in breast cancer patients receiving adjuvant chemotherapy consisting of cyclophosphamide, methotrexate and fluorouracil (CMF). Three hundred and sixty-eight patients with node-positive breast cancer without distant metastases were treated with six cycles of adjuvant CMF. Some patients (n = 60) also received tamoxifen. ⋯ Similarly, when the leucocyte nadir count was divided into tertiles, the patients who had the highest nadir values during the six-cycle treatment had worst outcome (RR 1.6, 95% CI 1.07-2.5, P = 0.02). However, in a multivariate analysis only the number of affected lymph nodes, tumour size, progesterone receptor status, surgical procedure, age and adjuvant tamoxifen therapy retained prognostic significance, whereas the leucocyte nadir count did not. A low leucocyte nadir during the adjuvant CMF chemotherapy is associated with favourable DDFS and it may be a useful biological marker for chemotherapy efficacy.