Robin J Lurvink1, Rudaba Tajzai1,2, Koen P Rovers1, Emma C E Wassenaar3, Dirk-Jan A R Moes4, Giulia Pluimakers2, Djamila Boerma3, Jacobus W A Burger1, Simon W Nienhuijs1, Ignace H J T de Hingh1,5, Maarten J Deenen6,7. 1. Department of Surgery, Catharina Hospital, Michelangelolaan 2, 5623 EJ, Eindhoven, The Netherlands. 2. Department of Clinical Pharmacy, Catharina Hospital Eindhoven, Michelangelolaan 2, 5623 EJ, Eindhoven, The Netherlands. 3. Department of Surgery, St. Antonius Hospital, Koekoekslaan 1, 3435 CM, Nieuwegein, The Netherlands. 4. Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, The Netherlands. 5. GROW - School for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands. 6. Department of Clinical Pharmacy, Catharina Hospital Eindhoven, Michelangelolaan 2, 5623 EJ, Eindhoven, The Netherlands. maarten.deenen@catharinaziekenhuis.nl. 7. Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, The Netherlands. maarten.deenen@catharinaziekenhuis.nl.
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.
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.
Authors: Koen P Rovers; Emma C E Wassenaar; Robin J Lurvink; Geert-Jan M Creemers; Jacobus W A Burger; Maartje Los; Clément J R Huysentruyt; Gesina van Lijnschoten; Joost Nederend; Max J Lahaye; Maarten J Deenen; Marinus J Wiezer; Simon W Nienhuijs; Djamila Boerma; Ignace H J T de Hingh Journal: Ann Surg Oncol Date: 2021-02-05 Impact factor: 5.344
Authors: Robin J Lurvink; Koen P Rovers; Emma C E Wassenaar; Checca Bakkers; Jacobus W A Burger; Geert-Jan M Creemers; Maartje Los; Floortje Mols; Marinus J Wiezer; Simon W Nienhuijs; Djamila Boerma; Ignace H J T de Hingh Journal: Surg Endosc Date: 2021-11-10 Impact factor: 3.453
Authors: C Bachmann; I Sautkin; G Nadiradze; R Archid; F J Weinreich; A Königsrainer; M A Reymond Journal: Surg Endosc Date: 2021-06-10 Impact factor: 4.584