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Mitomycin C Pharmacokinetics as Predictor of Severe Neutropenia in Hyperthermic Intraperitoneal Therapy

  • Gastrointestinal Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is an approach to overcome peritoneal carcinomatosis from colorectal adenocarcinoma. Mitomycin C (MMC) is frequently used but not devoid of toxicity, of which the most common and feared is neutropenia. Our study explores the clinical and surgical risk factors of neutropenia and a possible link between MMC pharmacokinetics and neutropenia as HIPEC’s supervention.

Methods

A total of 45 patients undergoing CRS-HIPEC for peritoneal carcinomatosis of colorectal origin between 2004 and 2010 were followed. For each patient, MMC was measured in plasma at different times during HIPEC and the area under the MMC concentration–time curve (MMC-AUC) was calculated.

Results

The incidence of neutropenia was 40 %. No demographic, clinical, or surgical factors increased the risk of neutropenia. However, we found that the occurrence of neutropenia and its gravity increased in direct correlation with an increase in MMC plasma concentration 30 min (T30) and 45 min (T45) after the start of HIPEC. The same correlation was observed between the MMC-AUC and the risk of neutropenia.

Conclusions

Neutropenia is a frequent complication associated with MMC-HIPEC. The results of our study indicate the feasibility and the potential benefit of a protocol including the MMC dosage at T30 after the start of HIPEC. A threshold of 572 µg/L gives a predictive sensitivity of 86 % and a specificity of 80 %. These results must be considered in the management of patients undergoing MMC-HIPEC in order to place high-risk patients under neutropenic monitoring while the other patients can undergo simple hematological monitoring.

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Acknowledgments

The authors want to thank Christian Ledunois, Muriel Jung, and Marie Rose Carle for their technical assistance and Dr. Maes for his English writing assistance.

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Authors and Affiliations

  1. Laboratoire de Biochimie et Biologie Moléculaire, Hôpitaux Universitaire de Strasbourg, Strasbourg, France

    Véronique Kemmel Pharm, PhD, Daniel Brumaru MD & Jean-Marc Lessinger Pharm, PhD

  2. Biopathologie de la Myéline, Neuroprotection et Stratégies Thérapeutiques, INSERM U-1119, Université de Strasbourg, Strasbourg, France

    Véronique Kemmel Pharm, PhD

  3. Service de Chirurgie Générale et Digestive, Hôpitaux Universitaire de Strasbourg, Strasbourg, France

    Henri-Alexis Mercoli MD, Benoit Romain MD, PhD & Cécile Brigand MD, PhD

  4. Faculté de médecine, Laboratoire de Biostatistiques, Strasbourg, France

    Nicolas Meyer MD, PhD

  5. Service de Santé Publique, Hôpitaux Universitaire de Strasbourg, Strasbourg, France

    Nicolas Meyer MD, PhD

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  1. Véronique Kemmel Pharm, PhD
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  2. Henri-Alexis Mercoli MD
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Correspondence to Véronique Kemmel Pharm, PhD.

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Kemmel, V., Mercoli, HA., Meyer, N. et al. Mitomycin C Pharmacokinetics as Predictor of Severe Neutropenia in Hyperthermic Intraperitoneal Therapy. Ann Surg Oncol 22 (Suppl 3), 873–879 (2015). https://doi.org/10.1245/s10434-015-4679-9

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  • DOI: https://doi.org/10.1245/s10434-015-4679-9

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