title: Capped-dose mitomycin C: a pooled safety analysis from three prospective clinical trials.
abstract: BACKGROUND
  Mitomycin C (MMC) up-regulates topoisomerase-I and thymidine phosphorylase making it ideal to combine with irinotecan or capecitabine. One of the most devastating toxicities MMC has been associated with is thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS) in 4-15% of patients, especially when receiving cumulative doses higher than 60 mg/m(2).
  
  
  METHODS
  We conducted a pooled safety analysis of 140 patients enrolled in three prospective clinical trials at our institution from 2001 to 2008. MMC on all our studies was capped to a cumulative dose of 36 mg/m(2) to limit toxicity while retaining efficacy. We reviewed our electronic medical records and clinical trial database for individual patient data on these studies with a specific intent to identify patients meeting criteria for TTP/HUS.
  
  
  RESULTS
  In combination with irinotecan or capecitabine, MMC was associated with manageable toxicities. We found no cases of MMC-associated TTP/HUS. There were no reported cardiac or pulmonary toxicities in our analysis. Most common grade 3/4 toxicities were diarrhea (19%), neutropenia (17%) and dehydration (12%) predominantly when MMC was combined with irinotecan.
  
  
  CONCLUSIONS
  In this large pooled analysis, we found MMC, when capped at a cumulative dose of 36 mg/m(2), to be safe and tolerable in combination with capecitabine or irinotecan with no reportable cases of TTP/HUS.
authors.affiliation: Department of Medicine, The Ohio State University, Columbus, USA.
authors.forename: Nse
authors.initials: N
authors.lastname: Ntukidem
authors.forename: Carlos
authors.initials: C
authors.lastname: Arce-Lara
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Otterson
authors.forename: Eric
authors.initials: E
authors.lastname: Kraut
authors.forename: Spero
authors.initials: S
authors.lastname: Cataland
authors.forename: Tanios
authors.initials: T
authors.lastname: Bekaii-Saab
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D000069287:Capecitabine; D002986:Clinical Trials as Topic; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006463:Hemolytic-Uremic Syndrome / Q000139:chemically induced; D006801:Humans; D000077146:Irinotecan; D016685:Mitomycin / Q000008:administration & dosage / Q000009:adverse effects*; D011446:Prospective Studies; D011697:Purpura, Thrombotic Thrombocytopenic / Q000139:chemically induced
chemical_list: D003841:Deoxycytidine; D016685:Mitomycin; D000069287:Capecitabine; D000077146:Irinotecan; D005472:Fluorouracil; D002166:Camptothecin