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

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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.

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Conflict of interest statement

Tanios Bekaii-Saab: Reasearch Funding (Roche, Genentech and Pfizer), Remuneration (Genentech). Gregory Otterson: Research funding (Genentech, Pfizer, Abraxis).

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Authors and Affiliations

  1. Department of Medicine, The Ohio State University, B407 Starling Loving Hall, 320 West 10th Avenue, 43206, Columbus, OH, USA

    Nse Ntukidem, Carlos Arce-Lara, Gregory A. Otterson, Eric Kraut, Spero Cataland & Tanios Bekaii-Saab

  2. Department of Pharmacology, The Ohio State University, Columbus, OH, USA

    Tanios Bekaii-Saab

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  1. Nse Ntukidem
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  2. Carlos Arce-Lara
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Correspondence to Tanios Bekaii-Saab.

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Ntukidem, N., Arce-Lara, C., Otterson, G.A. et al. Capped-dose mitomycin C: a pooled safety analysis from three prospective clinical trials. Cancer Chemother Pharmacol 65, 319–324 (2010). https://doi.org/10.1007/s00280-009-1036-3

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