Capped-dose mitomycin C: a pooled safety analysis from three prospective clinical trials.
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.
Ntukidem
Nse
N
Department of Medicine, The Ohio State University, Columbus, USA.
Arce-Lara
Carlos
C
Otterson
Gregory A
GA
Kraut
Eric
E
Cataland
Spero
S
Bekaii-Saab
Tanios
T
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
D003841:Deoxycytidine; D016685:Mitomycin; D000069287:Capecitabine; D000077146:Irinotecan; D005472:Fluorouracil; D002166:Camptothecin