Gynecologic Oncology

Annals of Surgical Oncology

, Volume 15, Issue 4, pp 1183-1192

First online:

Cytoreductive Surgery and Intraoperative Hyperthermic Intraperitoneal Chemotherapy with Paclitaxel: A Clinical and Pharmacokinetic Study

  • Eelco de BreeAffiliated withDepartment of Surgical Oncology, University Hospital, Crete University Medical School Email author 
  • , Hilde RosingAffiliated withDepartment of Pharmacy and Pharmacology, Slotervaart Hospital/The Netherlands Cancer Institute
  • , Dimitris FilisAffiliated withDepartment of Surgical Oncology, University Hospital, Crete University Medical School
  • , John RomanosAffiliated withDepartment of Surgical Oncology, University Hospital, Crete University Medical School
  • , Maria MelisssourgakiAffiliated withDepartment of Surgical Oncology, University Hospital, Crete University Medical School
  • , Markos DaskalakisAffiliated withDepartment of Surgical Oncology, University Hospital, Crete University Medical School
  • , Maria PilatouAffiliated withDepartment of Surgical Oncology, University Hospital, Crete University Medical School
  • , Elias SanidasAffiliated withDepartment of Surgical Oncology, University Hospital, Crete University Medical School
  • , Panagiotis TaflampasAffiliated withDepartment of Surgical Oncology, University Hospital, Crete University Medical School
    • , Konstantinos KalbakisAffiliated withDepartment of Medical Oncology, University Hospital, Crete University Medical School
    • , Jos H. BeijnenAffiliated withDepartment of Pharmacy and Pharmacology, Slotervaart Hospital/The Netherlands Cancer Institute
    • , Dimitris D. TsiftsisAffiliated withDepartment of Surgical Oncology, University Hospital, Crete University Medical School

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Abstract

Background

Intraperitoneal chemotherapy has been recommended as a treatment option for ovarian cancer with peritoneal dissemination. Although its treatment duration is significantly shorter, intraoperative hyperthermic intraperitoneal perfusion chemotherapy (HIPEC) has several advantages over simple intraperitoneal instillation chemotherapy. While platinum compounds have usually been used, only a few have administered paclitaxel during HIPEC. Its large molecular weight suggests a much more favorable pharmacokinetic profile than that of platinum compounds. The pharmacokinetics of paclitaxel during and after HIPEC have not been studied before.

Methods

Thirteen women, mainly with ovarian cancer, underwent cytoreductive surgery and HIPEC with 175 mg/m2 paclitaxel for 2 h. Morbidity was noted. Peritoneal fluid samples and blood samples were harvested during and until 5 days after HIPEC for pharmacokinetic study in ten patients.

Results

No treatment-related mortality was noted. Overall morbidity was 38% (two wound infections, one deep venous thrombosis, two grade 1 thrombopenia, one grade 2 neutropenia, and one grade 3 pancytopenia). Mean maximal intraperitoneal paclitaxel concentration was 101 mg/L, which was an average of 1178 times higher than the peak plasma levels. The peritoneal fluid versus plasma AUC ratio was 1462 for the 2-h HIPEC duration and 366 for the total 5-day study period. Cytotoxic drug concentrations were detected in peritoneal fluid for a mean period of 2.7 days, despite drainage of the drug solution after 2 h of treatment.

Conclusions

HIPEC with paclitaxel following cytoreductive surgery is feasible, relatively safe, and associated with a highly favorable pharmacokinetic profile, despite its short treatment duration. Larger studies with a more homogenous patient cohort and adequate follow-up should be performed to demonstrate its efficacy.