title: Mitomycin C Pharmacokinetics as Predictor of Severe Neutropenia in Hyperthermic Intraperitoneal Therapy.
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.
authors.affiliation: Laboratoire de Biochimie et Biologie Moléculaire, Hôpitaux Universitaire de Strasbourg, Strasbourg, France. kemmel@unistra.fr.|Biopathologie de la Myéline, Neuroprotection et Stratégies Thérapeutiques, INSERM U-1119, Université de Strasbourg, Strasbourg, France. kemmel@unistra.fr.
authors.forename: Véronique
authors.initials: V
authors.lastname: Kemmel
authors.affiliation: Service de Chirurgie Générale et Digestive, Hôpitaux Universitaire de Strasbourg, Strasbourg, France.
authors.forename: Henri-Alexis
authors.initials: HA
authors.lastname: Mercoli
authors.affiliation: Faculté de médecine, Laboratoire de Biostatistiques, Strasbourg, France.|Service de Santé Publique, Hôpitaux Universitaire de Strasbourg, Strasbourg, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Meyer
authors.affiliation: Laboratoire de Biochimie et Biologie Moléculaire, Hôpitaux Universitaire de Strasbourg, Strasbourg, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Brumaru
authors.affiliation: Service de Chirurgie Générale et Digestive, Hôpitaux Universitaire de Strasbourg, Strasbourg, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: Romain
authors.affiliation: Laboratoire de Biochimie et Biologie Moléculaire, Hôpitaux Universitaire de Strasbourg, Strasbourg, France.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Lessinger
authors.affiliation: Service de Chirurgie Générale et Digestive, Hôpitaux Universitaire de Strasbourg, Strasbourg, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Brigand
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000556:secondary / Q000628:therapy; D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects* / Q000493:pharmacokinetics; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D010478:Chemotherapy, Cancer, Regional Perfusion; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000628:therapy; D003131:Combined Modality Therapy; D065426:Cytoreduction Surgical Procedures; D005260:Female; D005500:Follow-Up Studies; D005602:France / Q000453:epidemiology; D006801:Humans; D006979:Hyperthermia, Induced; D015994:Incidence; D007263:Infusions, Parenteral; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000009:adverse effects* / Q000493:pharmacokinetics; D009367:Neoplasm Staging; D009503:Neutropenia / Q000139:chemically induced / Q000453:epidemiology*; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000556:secondary / Q000628:therapy; D011379:Prognosis; D015996:Survival Rate; D014018:Tissue Distribution; D055815:Young Adult
chemical_list: D000903:Antibiotics, Antineoplastic; D016685:Mitomycin