title: Factors affecting platinum concentrations in human surgical tumour specimens after cisplatin.
abstract: We assessed factors which affect cisplatin concentrations in human surgical tumour specimens. Cisplatin 10 mg m-2 was given i.v. to 45 consenting patients undergoing surgical resection of neoplasms, and platinum was assayed in resected tumour and in deproteinated plasma by flameless atomic absorption spectrophotometry. By multiple stepwise regression analysis of normalised data, patient characteristics that emerged as being most closely associated (P < 0.05) with tumour platinum concentrations (after correcting for associations with other variables) were tumour 'source' [primary brain lymphomas, medulloblastomas and meningiomas ('type LMM') > 'others' > lung cancer > head/neck cancer > gliomas) or tumour 'type' (LMM > brain metastases > extracerebral tumours > gliomas), serum calcium and chloride (positive correlations) and bilirubin (negative). Tumour location (intracranial vs extracranial) did not correlate with platinum concentrations. If values for a single outlier were omitted, high-grade gliomas had significantly higher platinum concentrations (P < 0.003) than low-grade gliomas. For intracranial tumours, the computerised tomographic scan feature that correlated most closely with platinum concentrations in multivariate analysis was the darkness of peritumoral oedema. Tumour source or type is a much more important correlate of human tumour cisplatin concentrations than is intracranial vs extracranial location. Serum calcium, chloride and bilirubin levels may affect tumour cisplatin uptake or retention. CT scan characteristics may help predict cisplatin concentrations in intracranial tumours.
authors.affiliation: Ontario Cancer Treatment and Research Foundation, Ottawa Regional Cancer Centre, Canada.
authors.forename: D J
authors.initials: DJ
authors.lastname: Stewart
authors.forename: J M
authors.initials: JM
authors.lastname: Molepo
authors.forename: R M
authors.initials: RM
authors.lastname: Green
authors.forename: V A
authors.initials: VA
authors.lastname: Montpetit
authors.forename: H
authors.initials: H
authors.lastname: Hugenholtz
authors.forename: A
authors.initials: A
authors.lastname: Lamothe
authors.forename: N Z
authors.initials: NZ
authors.lastname: Mikhael
authors.forename: M D
authors.initials: MD
authors.lastname: Redmond
authors.forename: M
authors.initials: M
authors.lastname: Gadia
authors.forename: R
authors.initials: R
authors.lastname: Goel
mesh_terms: D001812:Blood-Brain Barrier; D001932:Brain Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000601:surgery; D002528:Cerebellar Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000601:surgery; D002945:Cisplatin / Q000493:pharmacokinetics*; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008223:Lymphoma / Q000188:drug therapy / Q000378:metabolism / Q000601:surgery; D008297:Male; D008527:Medulloblastoma / Q000188:drug therapy / Q000378:metabolism / Q000601:surgery; D008579:Meningioma / Q000188:drug therapy / Q000378:metabolism / Q000601:surgery; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000601:surgery; D010984:Platinum / Q000493:pharmacokinetics*
chemical_list: D010984:Platinum; D002945:Cisplatin