title: Heated (37 degrees C) oxaliplatin infusion in combination with capecitabine for metastatic colorectal carcinoma: can it reduce neuropathy?
abstract: OBJECTIVE
  Oxaliplatin-associated neuropathy remains a dose-limiting toxicity of the standard chemotherapy regimen of oxaliplatin and capecitabine for metastatic colorectal cancer. No preventive strategy has definitively been established. Because this neuropathy is triggered by cold, we hypothesized that infusing oxaliplatin at 37 degrees C might reduce neuropathy.
  
  
  METHODS
  In this open-label pilot feasibility trial, patients with no prior chemotherapy for metastatic colorectal cancer were included. Treatment consisted of capecitabine 1,000 mg/m(2) bid on days 1-14 and oxaliplatin 130 mg/m2 on day 1 of a 21-day cycle. The oxaliplatin infusion was administered through a fluid-warming device at a constant temperature of 37 degrees C over 2 h. The primary endpoint was feasibility and drug reactions during the infusion. Secondary endpoints included acute and chronic neuropathy as well as response rate.
  
  
  RESULTS
  Twenty patients were enrolled, and a total of 95 cycles administered. Median cumulative oxaliplatin dose was 735 mg/m(2). Apart from one patient with laryngeal spasm, no other infusion-related adverse events were observed. Of the patients, 35% reported grade 3/4 acute dysesthesia or paresthesia according to a patients questionnaire. Chronic neuropathy according to NCI CTC v3.0 was observed in 85% (grade 1) and 15% (grade 2), respectively. The overall response rate was 45% (95% CI 23-67%; 5% complete remission; 40% partial remission) and stable disease was achieved in another 30% of patients.
  
  
  CONCLUSIONS
  Administration of heated oxaliplatin in combination with capecitabine is feasible and well tolerated without additional toxicity. While we have observed a relatively low rate of chronic cumulative neuropathy with heated oxaliplatin, this procedure appears not promising enough for us to recommend its further clinical evaluation.
authors.affiliation: Medical Oncology, Kantonsspital Graubünden, Chur, Switzerland. richard.cathomas@ksgr.ch
authors.forename: Richard
authors.initials: R
authors.lastname: Cathomas
authors.forename: Dieter
authors.initials: D
authors.lastname: Köberle
authors.forename: Thomas
authors.initials: T
authors.lastname: Ruhstaller
authors.forename: Gisela
authors.initials: G
authors.lastname: Mayer
authors.forename: Andrea
authors.initials: A
authors.lastname: Räss
authors.forename: Ulrich
authors.initials: U
authors.lastname: Mey
authors.forename: Roger
authors.initials: R
authors.lastname: von Moos
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D000069287:Capecitabine; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005240:Feasibility Studies; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006358:Hot Temperature; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D020258:Neurotoxicity Syndromes / Q000209:etiology / Q000517:prevention & control*; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D010865:Pilot Projects; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil