Systemic exposure to cisplatin and paclitaxel after intraperitoneal chemotherapy in ovarian cancer
-
Published:2023-03
Issue:3
Volume:91
Page:247-256
-
ISSN:0344-5704
-
Container-title:Cancer Chemotherapy and Pharmacology
-
language:en
-
Short-container-title:Cancer Chemother Pharmacol
Author:
de Jong Loek A. W.ORCID, Lambert Marie, van Erp Nielka P., de Vries Lukas, Chatelut Etienne, Ottevanger Petronella B.
Abstract
Abstract
Purpose
To determine the systemic exposure to cisplatin and paclitaxel after adjuvant intraperitoneal administration in patients with advanced ovarian cancer who underwent primary debulking surgery. This could provide an explanation for the high incidence of systemic adverse events associated with this treatment regimen.
Methods
This is a prospective pharmacokinetic study in patients with newly diagnosed advanced ovarian cancer who were treated with intraperitoneal administered cisplatin and paclitaxel. Plasma and peritoneal fluid samples were obtained during the first treatment cycle. The systemic exposure to cisplatin and paclitaxel was determined and compared to previously published exposure data after intravenous administration. An exploratory analysis was performed to investigate the relation between systemic exposure to cisplatin and the occurrence of adverse events.
Results
Pharmacokinetics of ultrafiltered cisplatin were studied in eleven evaluable patients. The geometric mean [range] peak plasma concentration (Cmax) and area under the plasma-concentration time curve (AUC0–24 h) for cisplatin was 2.2 [1.8–2.7] mg/L and 10.1 [9.0–12.6] mg h/L, with a coefficient of variation (CV%) of 14 and 13.0%, respectively. The geometric mean [range] observed plasma concentration of paclitaxel was 0.06 [0.04–0.08] mg/L. No correlation was found between systemic exposure to ultrafiltered cisplatin and adverse events.
Conclusion
Systemic exposure to ultrafiltered cisplatin after intraperitoneal administration is high. In addition to a local effect, this provides a pharmacological explanation for high incidence of adverse events seen after intraperitoneal administration of high-dose cisplatin. The study was registered at ClinicalTrials.gov under registration number NCT02861872.
Publisher
Springer Science and Business Media LLC
Subject
Pharmacology (medical),Cancer Research,Pharmacology,Toxicology,Oncology
Reference28 articles.
1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68(6):394–424. https://doi.org/10.3322/caac.21492 2. Armstrong DK, Alvarez RD, Bakkum-Gamez JN, Barroilhet L, Behbakht K, Berchuck A, Berek JS, Chen LM, Cristea M, DeRosa M, ElNaggar AC, Gershenson DM, Gray HJ, Hakam A, Jain A, Johnston C, Leath CA III, Liu J, Mahdi H, Matei D, McHale M, McLean K, O’Malley DM, Penson RT, Percac-Lima S, Ratner E, Remmenga SW, Sabbatini P, Werner TL, Zsiros E, Burns JL, Engh AM (2019) NCCN guidelines insights: ovarian cancer, version 1.2019. J Natl Compr Canc Netw 17(8):896–909. https://doi.org/10.6004/jnccn.2019.0039 3. Moore K, Colombo N, Scambia G, Kim BG, Oaknin A, Friedlander M, Lisyanskaya A, Floquet A, Leary A, Sonke GS, Gourley C, Banerjee S, Oza A, Gonzalez-Martin A, Aghajanian C, Bradley W, Mathews C, Liu J, Lowe ES, Bloomfield R, DiSilvestro P (2018) Maintenance olaparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med 379(26):2495–2505. https://doi.org/10.1056/NEJMoa1810858 4. Gonzalez-Martin A, Pothuri B, Vergote I, DePont CR, Graybill W, Mirza MR, McCormick C, Lorusso D, Hoskins P, Freyer G, Baumann K, Jardon K, Redondo A, Moore RG, Vulsteke C, O’Cearbhaill RE, Lund B, Backes F, Barretina-Ginesta P, Haggerty AF, Rubio-Perez MJ, Shahin MS, Mangili G, Bradley WH, Bruchim I, Sun K, Malinowska IA, Li Y, Gupta D, Monk BJ, Investigators PE-OG- (2019) Niraparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med 381(25):2391–2402. https://doi.org/10.1056/NEJMoa1910962 5. Alberts DS, Liu PY, Hannigan EV, O’Toole R, Williams SD, Young JA, Franklin EW, Clarke-Pearson DL, Malviya VK, DuBeshter B (1996) Intraperitoneal cisplatin plus intravenous cyclophosphamide versus intravenous cisplatin plus intravenous cyclophosphamide for stage III ovarian cancer. N Engl J Med 335(26):1950–1955. https://doi.org/10.1056/NEJM199612263352603
|
|