For patients with refractory or relapsing testicular cancer after standard chemotherapy, more aggressive chemotherapy with carboplatin and etoposide may be used. After this high-dose chemotherapy, a stem cell transplant is performed to replace those that have been damaged or destroyed by the chemotherapy. The stem cells used in the transplant are taken from the patient’s blood before treatment, which is called an autologous peripheral blood stem cell transplant.

For this protocol consisting of high doses, our team made progress in terms of adapting the doses of carboplatin in a previous publication (Moeung et al, Clin Cancer Res 2017). For this work, it was to assess whether the calculation of doses of etoposide based on body surface area (that is, based on the patient’s weight and height) was appropriate.

We have confirmed that for these patients (who are relatively young men) the dose calculation in mg / m² is justified. Therapeutic pharmacological monitoring consisting of determining the plasma concentrations of the drug of which we have shown interest for carboplatin is not necessary for etoposide. This difference in terms of calculation of the doses (adjustment according to renal function then the concentrations observed for carboplatin; according to a single morphological criterion for etoposide) is explained by the different pharmacokinetic characteristics of these two drugs: elimination only renal for the first, both renal and hepatic with relatively limited variability between individuals for the second.

We also observed a correlation between a genetic characteristic that some patients had and the duration of their blood aplasia (ie the decrease in blood cell production due to chemotherapy). Patients with a mutation in a gene encoding the synthesis of an enzyme contributing to the metabolism of etoposide, UGT1A1, had more prolonged neutropenia. This result could also impact the response to treatment, which will need to be confirmed in future studies.

This study was carried out in collaboration with the Gustave Roussy Institute in Villejuif, the Léon Bérard Center in Lyon, the West Paul Papin Cancer Institute in Angers, the Paoli Calmettes Institute in Marseille, the Tenon Hospital of Paris, Clermont Ferrand University Hospital and Saint André Hospital in Bordeaux.

Discover the published article :

Pharm Res. 2020 Jul 16;37(7):147. doi: 10.1007/s11095-020-02861-5.
Pharmacokinetic and Pharmacogenetic Study of Etoposide in High-Dose Protocol (TI-CE) for Advanced Germ Cell Tumors
Sotheara Moeung , Christine Chevreau , Sabrina Marsili , Christophe Massart , Aude Fléchon, Rémy Delva , Gwenaëlle Gravis , Jean-Pierre Lotz , Jacques-Olivier Bay , Marine Gross-Goupil , Thomas Filleron , Caroline Delmas , Thierry Lafont , Etienne Chatelut,  Fabienne Thomas

Key words :

• Pharmacokinetics,
• pharmacogenetics,
• therapeutic intensification
• etoposide.
• germ cell tumors.
• High dose treatment.

Contact :

Etienne Chatelut
CRCT team 14 : Dose individualization of anticancer drugs
Mail : chatelut.etienne@iuct-oncopole.fr

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