Cancer Chemotherapy and Pharmacology

, Volume 65, Issue 2, pp 319–324

Capped-dose mitomycin C: a pooled safety analysis from three prospective clinical trials

  • Nse Ntukidem
  • Carlos Arce-Lara
  • Gregory A. Otterson
  • Eric Kraut
  • Spero Cataland
  • Tanios Bekaii-Saab
Original Article

DOI: 10.1007/s00280-009-1036-3

Cite this article as:
Ntukidem, N., Arce-Lara, C., Otterson, G.A. et al. Cancer Chemother Pharmacol (2010) 65: 319. doi:10.1007/s00280-009-1036-3
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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/m2.

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/m2 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/m2, to be safe and tolerable in combination with capecitabine or irinotecan with no reportable cases of TTP/HUS.

Keywords

Mitomycin CThrombotic thrombocytopenic purpuraHUSDose

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Nse Ntukidem
    • 1
  • Carlos Arce-Lara
    • 1
  • Gregory A. Otterson
    • 1
  • Eric Kraut
    • 1
  • Spero Cataland
    • 1
  • Tanios Bekaii-Saab
    • 1
    • 2
  1. 1.Department of MedicineThe Ohio State UniversityColumbusUSA
  2. 2.Department of PharmacologyThe Ohio State UniversityColumbusUSA