Back to Search
Start Over
Influence of tumour burden on trastuzumab pharmacokinetics in HER2 positive non-metastatic breast cancer.
- Source :
-
British Journal of Clinical Pharmacology . May2016, Vol. 81 Issue 5, p941-948. 8p. 2 Charts, 3 Graphs. - Publication Year :
- 2016
-
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. [ABSTRACT FROM AUTHOR]
- Subjects :
- *TRASTUZUMAB
*EPIDERMAL growth factor
*BREAST cancer
*PHARMACOKINETICS
*METASTASIS
Subjects
Details
- Language :
- English
- ISSN :
- 03065251
- Volume :
- 81
- Issue :
- 5
- Database :
- Academic Search Index
- Journal :
- British Journal of Clinical Pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 114604492
- Full Text :
- https://doi.org/10.1111/bcp.12875