We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Influence of tumour burden on trastuzumab pharmacokinetics in HER2 positive non-metastatic breast cancer.
- Authors
Bernadou, Guillemette; Campone, Mario; Merlin, Jean‐Louis; Gouilleux‐Gruart, Valérie; Bachelot, Thomas; Lokiec, François; Rezai, Keyvan; Arnedos, Monica; Diéras, Véronique; Jimenez, Marta; Paintaud, Gilles; Ternant, David
- Abstract
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 pre-operative trastuzumab. Methods Trastuzumab PK data were obtained from a multicentre, randomized and comparative study. This antibody was administered pre-operatively to patients with localized HER2-positive breast cancer as a single 4 mg kg−1 loading dose followed by 5 weekly 2 mg kg−1 doses. Trastuzumab concentrations were measured repeatedly using an ELISA technique. Tumour size was evaluated at baseline using breast echography. Trastuzumab pharmacokinetics were 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 from 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−1, with an elimination half-life of 11.8 days. Typical clearance was 0.22 l day−1 (19%) and its value was increased with tumour size. In patients 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.
- Subjects
TRASTUZUMAB; EPIDERMAL growth factor; BREAST cancer; PHARMACOKINETICS; METASTASIS
- Publication
British Journal of Clinical Pharmacology, 2016, Vol 81, Issue 5, p941
- ISSN
0306-5251
- Publication type
Article
- DOI
10.1111/bcp.12875