Abstract
Purpose
The pharmacokinetics of trabectedin has never been reported in patients with impaired renal function or in patients on hemodialysis.
Methods
We examined trabectedin PK in a patient on hemodialysis, starting trabectedin therapy at a standard dose for recurrence of a retroperitoneal myxoid liposarcoma that had occurred under immunosuppressive drugs for kidney transplant.
Results
As compared with a population with normal renal function, the study patient presented a higher C max and AUC, with lower clearance, terminal half-life, and volume of distribution. The low dialysis clearance, accounting for a minor part of the total body clearance and the absence of detectable trabectedin in the dialysate samples, suggests that hemodialysis does not efficiently clear trabectedin. Trabectedin tolerance was good.
Conclusions
This case reports for the first time the feasibility of trabectedin therapy in a hemodialyzed patient. Given the rising incidence of cancer in patients with end-stage renal disease, it is crucial to provide data that improve the management of anticancer drugs in dialyzed patients.
This is a preview of subscription content, log in via an institution to check access.
References
D’Incalci M, Galmarini CM (2010) A review of trabectedin (ET-743): a unique mechanism of action. Mol Cancer Ther 9:2157–2163
Beumer JH, Rademaker-Lakhai JM, Rosing H, Hillebrand MJ, Bosch TM, Lopez-Lazaro L, Schellens JH, Beijnen JH (2007) Metabolism of trabectedin (ET-743, Yondelis) in patients with advanced cancer. Cancer Chemother Pharmacol 59:825–837
Beumer JH, Schellens JH, Beijnen JH (2005) Hepatotoxicity and metabolism of trabectedin: a literature review. Pharmacol Res 51:391–398
Beumer JH, Lopez-Lazaro L, Schellens JH, Beijnen JH, van Tellingen O (2009) Evaluation of human plasma protein binding of trabectedin (Yondelis, ET-743). Curr Clin Pharmacol 4:38–42
Sparidans RW, Rosing H, Hillebrand MJ, López-Lázaro L, Jimeno JM, Manzanares I, van Kesteren C, Cvitkovic E, van Oosterom AT, Schellens JH, Beijnen JH (2001) Search for metabolites of ecteinascidin 743, a novel, marine-derived, anti-cancer agent, in man. Anticancer Drugs 12:653–666
Janus N, Thariat J, Boulanger H, Deray G, Launay-Vacher V (2010) Proposal for dosage adjustment and timing of chemotherapy in hemodialyzed patients. Ann Oncol 21:1395–1403
Thariat J, Azzopardi N, Peyrade F, Launay-Vacher V, Santini J, Lecomte T, Etienne-Grimaldi MC, Paintaud G, Milano G (2008) Cetuximab pharmacokinetics in end-stage kidney disease under hemodialysis. J Clin Oncol 26:4223–4225
Perez-Ruixo JJ, Zannikos P, Hirankarn S, Stuyckens K, Ludwig EA, Soto-Matos A, Lopez-Lazaro L, Owen JS (2007) Population pharmacokinetic meta-analysis of trabectedin (ET-743, Yondelis) in cancer patients. Clin Pharmacokinet 46:867–884
Rosing H, Hillebrand MJ, Jimeno JM, Gómez A, Floriano P, Faircloth G, Henrar RE, Vermorken JB, Cvitkovic E, Bult A, Beijnen JH (1998) Quantitative determination of Ecteinascidin 743 in human plasma by miniaturized high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry. J Mass Spectrom 33:1134–1140
Rosing H, Hillebrand MJ, Jimeno JM, Gómez A, Floriano P, Faircloth G, Cameron L, Henrar RE, Vermorken JB, Bult A, Beijnen JH (1998) Analysis of Ecteinascidin 743, a new potent marine-derived anticancer drug, in human plasma by high-performance liquid chromatography in combination with solid-phase extraction. J Chromatogr B Biomed Sci Appl 710:183–189
Penn I (1993) The effect of immunosuppression on pre-existing cancers. Transplantation 55:742–747
Demetri GD, Chawla SP, von Mehren M, Ritch P, Baker LH, Blay JY, Hande KR, Keohan ML, Samuels BL, Schuetze S, Lebedinsky C, Elsayed YA, Izquierdo MA, Gómez J, Park YC, Le Cesne A (2009) Efficacy and safety of trabectedin in patients with advanced or metastatic liposarcoma or leiomyosarcoma after failure of prior anthracyclines and ifosfamide: results of a randomized phase II study of two different schedules. J Clin Oncol 27:4188–4196
Puchalski TA, Ryan DP, Garcia-Carbonero R, Demetri GD, Butkiewicz L, Harmon D, Seiden MV, Maki RG, Lopez-Lazaro L, Jimeno J, Guzman C, Supko JG (2002) Pharmacokinetics of ecteinascidin 743 administered as a 24-h continuous intravenous infusion to adult patients with soft tissue sarcomas: associations with clinical characteristics, pathophysiological variables and toxicity. Cancer Chemother Pharmacol 50:309–319
Acknowledgments
Authors would like to thank Hervé C’leach (PharmaMar) for his logistic support.
Conflict of interest
A. Soto-Matos and C. Fernandez-Teruel work for PharmaMar. Other authors have none.
Author information
Authors and Affiliations
Corresponding author
Additional information
J. Thariat and M.-C. Etienne-Grimaldi contributed equally to the manuscript.
Rights and permissions
About this article
Cite this article
Thariat, J., Etienne-Grimaldi, MC., Launay-Vacher, V. et al. Pharmacokinetics of trabectedin on hemodialysis: an application for the management of cancer patients with end-stage renal disease. Cancer Chemother Pharmacol 68, 1363–1367 (2011). https://doi.org/10.1007/s00280-011-1718-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00280-011-1718-5