Annals of Surgical Oncology

, Volume 22, Supplement 3, pp 873–879 | Cite as

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

  • Véronique Kemmel
  • Henri-Alexis Mercoli
  • Nicolas Meyer
  • Daniel Brumaru
  • Benoit Romain
  • Jean-Marc Lessinger
  • Cécile Brigand
Gastrointestinal Oncology

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.

Keywords

Neutropenia Peritoneal Dissemination Severe Neutropenia Complete Cytoreduction Hyperthermic Intraperitoneal Chemotherapy 

Notes

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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Copyright information

© Society of Surgical Oncology 2015

Authors and Affiliations

  • Véronique Kemmel
    • 1
    • 2
  • Henri-Alexis Mercoli
    • 3
  • Nicolas Meyer
    • 4
    • 5
  • Daniel Brumaru
    • 1
  • Benoit Romain
    • 3
  • Jean-Marc Lessinger
    • 1
  • Cécile Brigand
    • 3
  1. 1.Laboratoire de Biochimie et Biologie MoléculaireHôpitaux Universitaire de StrasbourgStrasbourgFrance
  2. 2.Biopathologie de la Myéline, Neuroprotection et Stratégies Thérapeutiques, INSERM U-1119Université de StrasbourgStrasbourgFrance
  3. 3.Service de Chirurgie Générale et DigestiveHôpitaux Universitaire de StrasbourgStrasbourgFrance
  4. 4.Faculté de médecineLaboratoire de BiostatistiquesStrasbourgFrance
  5. 5.Service de Santé PubliqueHôpitaux Universitaire de StrasbourgStrasbourgFrance

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