Résumé
L’utilisation de la voie sous-cutanée (SC) pour l’administration des médicaments injectables permet une amélioration de la qualité de vie des patients et facilite le développement des alternatives à l’hospitalisation. Cependant, l’utilisation de cette voie a longtemps été limitée à certaines molécules, car elle nécessite de franchir la matrice extracellulaire (MEC) qui est une barrière à la diffusion des fluides dans l’espace SC. Après la découverte de l’hyaluronidase améliorant la diffusion des molécules, une version recombinante (rHuPH20) a été développée. Associé au médicament, le rHuPH20 a permis d’élargir l’utilisation de cette voie à de plus grosses molécules. Lors du développement des anticorps monoclonaux anticancéreux, la posologie était initialement adaptée à partir de critères tels que le poids du patient, permettant, en théorie, une meilleure exposition du patient au médicament. Cependant, de nombreux auteurs rapportent qu’une administration par dose fixe est globalement plus pertinente pour la majorité des anticorps monoclonaux. Dans cette revue, nous détaillons l’exemple du trastuzumab (Herceptin®), traitement standard du cancer du sein HER2 amplifié ou surexprimé, habituellement administré par voie intraveineuse (IV). Plusieurs travaux ont évalué l’intérêt de la voie SC (poids du patient) associée au rHuPH20 par rapport à la voie IV (poids du patient). D’autres travaux ont comparé une dose fixe de trastuzumab par voie SC (+ rHuPH20) à une dose adaptée selon le poids de la patiente et injectée en IV. Globalement, les différentes modalités d’administration semblent équivalentes en termes d’efficacité (néoadjuvant), de pharmacocinétique (PK) [aire sous la courbe, concentration résiduelle] et de toxicité.
Abstract
Subcutaneous (SC) administration of injectable medications allows an improved quality of life of patients and contributes to the development of alternatives to hospitalization. However, this route has long been limited to certain drugs because it requires the crossing of the extracellular matrix which is a barrier to the diffusion of fluids in the SC space. After the discovery of hyaluronidase, which improves the diffusion of molecules, a recombinant version (rHuPH20) has been developed. In association with the medication, rHuPH20 allowed to extend the use of the SC route to bigger molecules. When anticancer monoclonal antibodies were developed, dosage was initially adjusted based on criteria such as the patient’s weight, thereby leading theoretically to a better patient’s exposure to the drug. However, numerous authors reported that a fixed-dose administration was globally more relevant for the majority of monoclonal antibodies. In this review, we detail the example of the trastuzumab (Herceptin®) as standard treatment of amplified or overexpressed HER2 breast cancer, usually administered intravenously (IV). Several studies assessed the benefit of the SC route (patient’s weight) associated with rHuPH20 when compared with an IV administration (patient’s weight). Others compared a SC fixed dose of trastuzumab (+ rHuPH20) to an IV dose adapted to the patient’s weight. Overall, the different administration modalities seem equivalent in terms of efficacy (neoadjuvant), pharmacokinetics (including area under the curve and residual concentration) and toxicity.
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Pinguet, F., Milano, G. Biothérapies par voie sous-cutanée : modalités d’absorption et implications cliniques. Oncologie 16, 393–400 (2014). https://doi.org/10.1007/s10269-014-2445-4
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DOI: https://doi.org/10.1007/s10269-014-2445-4