title: Impact of long-term serum platinum concentrations on neuro- and ototoxicity in Cisplatin-treated survivors of testicular cancer.
abstract: OBJECTIVE
  Cisplatin-induced neurotoxicity and ototoxicity (NTX) are important adverse effects after chemotherapy for testicular cancer (TC). Although serum platinum is measurable years after therapy, its impact on NTX has not been evaluated.
  
  
  METHODS
  In all, 169 cisplatin-treated survivors of TC provided blood samples at Survey I and reported NTX during Survey I (1998-2002) and Survey II (2007-2008). Serum platinum was quantified by inductively coupled plasma mass spectrometry. Patient-reported outcomes were evaluated with the Scale for Chemotherapy-Induced Neurotoxicity (SCIN), regarding the extent of symptom bother as 0, "not at all"; 1, "a little"; 2, "quite a bit"; or 3, "very much." Summing the six symptom scores yielded a total SCIN score of 0 to 18. Categorizing total SCIN scores into quartiles yielded similar-sized groups with increasing symptoms. Multivariate ordinal logistic regression analyses evaluated associations between NTX and long-term serum platinum levels, adjusting for cisplatin dose, dosing schedule, and age.
  
  
  RESULTS
  At Survey I, a significant four- to five-fold association with total SCIN score emerged for the highest serum platinum quartile (odds ratio [OR], 4.69; 95% CI, 1.82 to 12.08). Paresthesias and Raynaud's syndrome (hands and feet) showed significant two- to four-fold increased risks with the highest platinum quartile. At Survey II, total SCIN score remained significantly associated with the highest platinum quartile (OR, 4.28; 95% CI, 1.36 to 13.48). Paresthesias (hands and feet) and tinnitus showed significant three- to four-fold increased risks for the highest platinum quartile. Cumulative cisplatin dose was not associated with total SCIN score or individual SCIN symptoms in multivariate analyses.
  
  
  CONCLUSIONS
  Here we document a significant relationship between increasing levels of residual serum platinum and NTX severity after adjusting for initial cisplatin dose.
authors.affiliation: Norwegian Radium Hospital-Oslo University Hospital, Oslo, Norway.
authors.forename: Mette
authors.initials: M
authors.lastname: Sprauten
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Darrah
authors.forename: Derick R
authors.initials: DR
authors.lastname: Peterson
authors.forename: M Ellen
authors.initials: ME
authors.lastname: Campbell
authors.forename: Robyn E
authors.initials: RE
authors.lastname: Hannigan
authors.forename: Milada
authors.initials: M
authors.lastname: Cvancarova
authors.forename: Clair
authors.initials: C
authors.lastname: Beard
authors.forename: Hege S
authors.initials: HS
authors.lastname: Haugnes
authors.forename: Sophie D
authors.initials: SD
authors.lastname: Fosså
authors.forename: Jan
authors.initials: J
authors.lastname: Oldenburg
authors.forename: Lois B
authors.initials: LB
authors.lastname: Travis
mesh_terms: D000293:Adolescent; D000328:Adult; D002945:Cisplatin / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D003051:Cochlea / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020258:Neurotoxicity Syndromes / Q000097:blood* / Q000209:etiology; D010984:Platinum / Q000097:blood*; D011795:Surveys and Questionnaires; D016019:Survival Analysis; D017741:Survivors; D013736:Testicular Neoplasms / Q000097:blood* / Q000188:drug therapy; D014432:Tympanic Membrane / Q000187:drug effects*; D055815:Young Adult
chemical_list: D010984:Platinum; D002945:Cisplatin