0 avis
Influence of tumour burden on trastuzumab pharmacokinetics in HER2 positive non-metastatic breast cancer
Archive ouverte
International audience. Aims. Trastuzumab, an antibody binding to epidermal growth factor receptor-2 (HER2), has been approved to treat HER2-positive breast cancer in different settings. This study aimed at evaluating the influence of tumour size on trastuzumab pharmacokinetics (PK) in non-metastatic breast cancer patients treated with short-term preoperative trastuzumab.Methods.Trastuzumab PK data were obtained from a multi-center, randomized and comparative study. This antibody was administered preoperatively to patients with localized HER2-positive breast cancer as a single 4 mg/kg loading dose followed by 5 weekly 2 mg/kg doses. Trastuzumab concentrations were measured repeatedly using an ELISA technique. Tumour size was evaluated at baseline using breast echography. Trastuzumab pharmacokinetics was studied using a population approach and a two-compartment model. The influence of tumour burden on trastuzumab pharmacokinetics was quantified as a covariate.Results.A total of 784 trastuzumab concentrations were available in the 79 eligible patients. Estimated parameters (interindiviual standard deviation) were: central volume of distribution = 2.1 L (23%), peripheral volume of distribution = 1.3 L (38%) intercompartment clearance = 0.36 L/day, with an elimination half-life of 11.8 days. Typical clearance was 0.22 L/day (19%) and its value was increased with tumour size: in patient with the highest tumour size, trastuzumab clearance was 50% [18%–92%] higher than in patients with the lowest tumour size.Conclusions.In non-metastatic breast cancer patients, trastuzumab clearance increases with tumour size. The elimination half-life of trastuzumab was shorter in the present population of patients than in metastatic breast cancer patients previously studied.
Consulter en ligne
Suggestions
Du même auteur
