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.