Comparative neurotoxicity of weekly non-break paclitaxel infusions over 1 versus 3 h
作者:
Stephan Mielke,
Klaus Mross,
Thomas Gerds,
Anja Schmidt,
Ralph Wäsch,
Dietmar Berger,
Winand Lange,
Dirk Behringer,
期刊:
Anti-Cancer Drugs
(OVID Available online 2003)
卷期:
Volume 14,
issue 10
页码: 785-792
ISSN:0959-4973
年代: 2003
出版商: OVID
关键词: neurotoxicity;paclitaxel;phase III trial;solid tumor;weekly regimen
数据来源: OVID
摘要:
We evaluated the effects of weekly short infusions of paclitaxel (PAC) on the development of a peripheral neuropathy (PNP) as primary endpoint. Patients with advanced cancer were randomized to a weekly regimen of PAC (100 mg/m2) infused over 1 versus 3 h. PNP was evaluated by a clinical score including sensory symptoms, strength, tendon reflexes and vibratory sense (range 0–12; PNP >3 points). Kaplan–Meier-type curves were calculated. In total, 22 study centers enrolled 121 patients, 92 assessable for analysis. The probability to exceed a PNP score of 3 increased from 0.20 versus 0.30 after six to 0.68 versus 0.47 after 12 administrations (1 versus 3 h:p = 0.66). After 12 weeks of therapy only a quarter of assessable patients were free of PNP. Cox analysis yielded a relative risk of 1.10 for 1-h infusions (p = 0.80). We observed a rapid increasing risk of PNP manifestation in the course of weekly PAC administrations without significant differences between 1- and 3-h infusions. This is in contrast to pharmacokinetic observations indicating that a shortening of infusion time might enhance neurotoxicity by increasing the AUC of Cremophor. A majority of patients experiencing neurotoxic effects require the investigation of potential nerve protectors in future clinical trials accompanying PAC therapy.
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