title: Neurotoxicity is not enhanced by increased dose intensities of cisplatin administration.
abstract: It is uncertain whether intensive dosing schedules of cisplatin, intended to attain a higher anti-tumour efficacy, alter the severity of cisplatin-induced neuropathy. We assessed the development of neuropathy in three groups of patients treated with cisplatin in different dosing schedules. The severity of neuropathy was determined by measurement of the vibration perception threshold (VPT) before treatment and during follow-up for 2-12 months after the last cycle. 66 patients were treated with an intensive weekly regimen of doses varying from 70 to 85 mg/m2 in 1 day (trial A), 21 patients with a 3-weekly combination chemotherapy containing cisplatin 75 mg/m2 in 1 day (trial B) and 20 patients with a 3-weekly regimen containing cisplatin 20 mg/m2 for 5 consecutive days (trial C). The mean dose intensity achieved was 59 mg/m2/week in trial A, 21 mg/m2/week in trial B and 33 mg/m2/week in trial C. The maximum post-treatment VPT correlated significantly with pretreatment VPT (P < 0.001) and with the cumulative dose of cisplatin (P < 0.001). Following correction for these two variables, the maximum posttreatment VPT did not show a statistically significant association with dose intensity. These results suggest that neuropathy is not related to dose intensity of cisplatin. This implies that treatment with more intensive dosing schedules, employing equal cumulative doses of cisplatin, does not result in a concomitant increase in neurotoxicity within a cumulative dose range of 280-675 mg/m2.
authors.affiliation: Department of Neuro-Oncology, Dr Daniel den Hoed Cancer Center and University Hospital, Rotterdam, The Netherlands.
authors.forename: P H
authors.initials: PH
authors.lastname: Hilkens
authors.forename: M E
authors.initials: ME
authors.lastname: van der Burg
authors.forename: J W
authors.initials: JW
authors.lastname: Moll
authors.forename: A S
authors.initials: AS
authors.lastname: Planting
authors.forename: W L
authors.initials: WL
authors.lastname: van Putten
authors.forename: C J
authors.initials: CJ
authors.lastname: Vecht
authors.forename: M J
authors.initials: MJ
authors.lastname: van den Bent
mesh_terms: D000293:Adolescent; D000324:Adrenocorticotropic Hormone / Q000031:analogs & derivatives / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000627:therapeutic use; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects*; D017322:Clinical Trials, Phase II as Topic; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009420:Nervous System / Q000187:drug effects*; D009422:Nervous System Diseases / Q000139:chemically induced* / Q000517:prevention & control; D010446:Peptide Fragments / Q000627:therapeutic use; D010465:Perception / Q000187:drug effects; D014732:Vibration
chemical_list: D000927:Anticonvulsants; D010446:Peptide Fragments; C013765:Org 2766; D000324:Adrenocorticotropic Hormone; D002945:Cisplatin