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Systemic Pharmacokinetics of Oxaliplatin After Intraperitoneal Administration by Electrostatic Pressurized Intraperitoneal Aerosol Chemotherapy (ePIPAC) in Patients with Unresectable Colorectal Peritoneal Metastases in the CRC-PIPAC Trial

  • Peritoneal Surface Malignancy
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Electrostatic pressurized intraperitoneal aerosol chemotherapy (ePIPAC) is a palliative treatment for unresectable peritoneal metastases from various primary cancers. However, little is known about the systemic pharmacokinetics of oxaliplatin after ePIPAC.

Methods

Twenty patients with unresectable colorectal peritoneal metastases were treated with repetitive ePIPAC monotherapy with oxaliplatin (92 mg/m2) and a simultaneous intravenous bolus of leucovorin (20 mg/m2) and 5-fluorouracil (400 mg/m2). Samples were collected during each ePIPAC: whole blood at t = 0, t = 5, t = 10, t = 20, t = 30, t = 60, t = 120, t = 240, t = 360 and t = 1080 min for plasma and plasma ultrafiltrate concentrations; urine at t = 0, t = 1, t = 3, t = 5 and t = 7 days. Samples were analyzed using atomic absorption spectrometry. Pharmacokinetics were analyzed using nonlinear mixed-effects modeling.

Results

Four patients received one ePIPAC, three patients received two ePIPAC, and thirteen patients received ≥ 3 ePIPAC. The population pharmacokinetic models adequately described the pharmacokinetics of oxaliplatin after ePIPAC. The plasma ultrafiltrate Cmax of oxaliplatin reached 1.36–1.90 µg/mL after 30 min with an AUC0–24 h of 9.6–11.7 µg/mL * h. The plasma Cmax reached 2.67–3.28 µg/mL after 90 min with an AUC0–24 h of 49.0–59.5 µg/mL * h. The absorption rate constant (Ka) was 1.13/h. Urine concentrations of oxaliplatin rapidly decreased to less than 3.60 µg/mL in 90% of the samples at day 7.

Discussion

Systemic exposure to oxaliplatin after ePIPAC seemed comparable to that after systemic chemotherapy, as described in other literature. Since this is an indirect comparison, future research should focus on the direct comparison between the systemic exposure to oxaliplatin after ePIPAC and after systemic chemotherapy.

Trial registration: NCT03246321, Pre-results; ISRCTN89947480, Pre-results; NTR6603, Pre-results; EudraCT: 2017-000927-29, Pre-results.

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Acknowledgement

This study received funding from the Catharina Research Foundation and the St. Antonius Research Foundation.

Author information

Author notes

  1. Robin J. Lurvink and Rudaba Tajzai contributed equally to this manuscript and share the first authorship.

Authors and Affiliations

  1. Department of Surgery, Catharina Hospital, Michelangelolaan 2, 5623 EJ, Eindhoven, The Netherlands

    Robin J. Lurvink MD, Rudaba Tajzai BSc, Koen P. Rovers MD, Jacobus W. A. Burger MD PhD, Simon W. Nienhuijs MD PhD & Ignace H. J. T. de Hingh MD PhD

  2. Department of Clinical Pharmacy, Catharina Hospital Eindhoven, Michelangelolaan 2, 5623 EJ, Eindhoven, The Netherlands

    Rudaba Tajzai BSc, Giulia Pluimakers BSc & Maarten J. Deenen PharmD PhD

  3. Department of Surgery, St. Antonius Hospital, Koekoekslaan 1, 3435 CM, Nieuwegein, The Netherlands

    Emma C. E. Wassenaar MD & Djamila Boerma MD PhD

  4. Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, The Netherlands

    Dirk-Jan A. R. Moes PharmD PhD & Maarten J. Deenen PharmD PhD

  5. GROW - School for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands

    Ignace H. J. T. de Hingh MD PhD

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  1. Robin J. Lurvink MD
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Correspondence to Maarten J. Deenen PharmD PhD.

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Lurvink, R.J., Tajzai, R., Rovers, K.P. et al. Systemic Pharmacokinetics of Oxaliplatin After Intraperitoneal Administration by Electrostatic Pressurized Intraperitoneal Aerosol Chemotherapy (ePIPAC) in Patients with Unresectable Colorectal Peritoneal Metastases in the CRC-PIPAC Trial. Ann Surg Oncol 28, 265–272 (2021). https://doi.org/10.1245/s10434-020-08743-9

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