AIMS AND BACKGROUND: Lapatinib is a tyrosine kinase inhibitor targeting epidermal growth factor receptors 1 (EGFR/HER1) and 2 (HER2) used in the treatment of patients with HER2-positive breast cancer. The aim of the present study was to determine lapatinib plasma levels in breast cancer patients treated with lapatinib plus capecitabine. PATIENTS AND METHODS: We assessed lapatinib plasma levels in blood samples from 21 breast cancer patients treated with lapatinib plus capecitabine using the standard regimen in an expanded access program. Liquid chromatography tandem mass spectrometry was used for measuring lapatinib plasma concentrations. The validated method was applied for measurement of 55 plasma samples. RESULTS: The median lapatinib plasma level was 5.09 μg/mL, with large interindividual differences. Patients of lower weight tended to have higher lapatinib plasma levels (Spearman correlation coefficient R = -0.435, P = 0.055). One patient's lapatinib plasma levels were markedly higher than those of the others, with a median level of 11.25 μg/mL and repeatedly exceeding 7.80 μg/mL. The treatment was terminated after 8 months when hyperbilirubinemia occurred. CONCLUSIONS: The lapatinib plasma levels reported here are twice as high as the clinically effective steady-state geometric mean maximum concentration. We conclude that increased lapatinib body levels occur when patients are in a nonfasting state at the time of drug intake and when lapatinib doses are not adjusted to low body weight or weight loss during treatment. In Europe, dose adjustments are not recommended in the case of hepatic function impairment. Thus, attention should be paid to changes in liver function test results in clinical practice, especially in patients of small stature and weight, given the risk of high plasma concentrations. Prospective lapatinib plasma level assessment in treated patients might be useful to confirm or refute the possible correlation of high lapatinib plasma levels with hepatic and/or other toxicities.
- MeSH
- chinazoliny aplikace a dávkování krev MeSH
- chromatografie kapalinová MeSH
- deoxycytidin aplikace a dávkování analogy a deriváty MeSH
- dospělí MeSH
- fluorouracil aplikace a dávkování analogy a deriváty MeSH
- hyperbilirubinemie chemicky indukované MeSH
- inhibitory proteinkinas aplikace a dávkování krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádorové biomarkery krev MeSH
- nádory prsu krev farmakoterapie patologie MeSH
- prediktivní hodnota testů MeSH
- prospektivní studie MeSH
- protokoly antitumorózní kombinované chemoterapie terapeutické užití MeSH
- retrospektivní studie MeSH
- senioři MeSH
- staging nádorů MeSH
- stupeň nádoru MeSH
- tandemová hmotnostní spektrometrie MeSH
- tyrosinkinasy antagonisté a inhibitory MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Publikační typ
- abstrakt z konference MeSH
- MeSH
- adjuvantní chemoterapie * metody využití MeSH
- geny erbB-1 účinky léků MeSH
- geny erbB-2 * účinky léků MeSH
- humanizované monoklonální protilátky aplikace a dávkování terapeutické užití MeSH
- klinické zkoušky jako téma MeSH
- lidé MeSH
- nádory prsu * diagnóza genetika terapie MeSH
- statistika jako téma MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- práce podpořená grantem MeSH
BACKGROUND: Collagen triple helix repeat containing 1 (CTHRC1) affects Wnt signalling, collagen deposition and bone formation. It is an extracellular matrix protein which is also abnormally expressed in the tumour microenvironment. CTHRC1 has not been studied in breast cancer by immunohistochemistry. AIMS: To examine expression of CTHRC1 together with periostin and versican in breast cancer patients and investigate its association with clinicopathological characteristics. METHODS: The formalin-fixed paraffin-embedded tissues of 173 invasive carcinomas (classified into WHO histotypes and luminal, triple negative and Her2 subtypes), as well as normal tissues, precursor lesions and metastatic lymph nodes were stained by relevant antibodies, assessed semiquantitatively by histoscore and statistically evaluated. RESULTS: Expression of CTHRC1, versican and periostin was significantly higher in breast cancer than in normal tissue or precursor lesions. CTHRC1 stromal expression was enhanced in triple negative cases and also in patients with bone metastasis. Periostin expression was high in primary tumours, in particular triple negative ones, and also in their lymph node metastases. Cox regression analysis showed that in patients with high periostin, the risk of bone metastases increased with increased CTHRC1 expression. CONCLUSIONS: CTHRC1 and periostin play important roles in breast cancer progression. These preliminary results show that combined evaluation of CTHRC1 and periostin could serve as a potential marker for breast cancer bone metastasis; the other observations contribute to the description of the tumour microenvironment, with implications for lymph node and bone metastasis.
- MeSH
- dospělí MeSH
- extracelulární matrix - proteiny metabolismus MeSH
- imunohistochemie MeSH
- lidé středního věku MeSH
- lidé MeSH
- lymfatické metastázy MeSH
- molekuly buněčné adheze metabolismus MeSH
- nádorové biomarkery metabolismus MeSH
- nádory kostí metabolismus sekundární MeSH
- nádory prsu metabolismus MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- versikany metabolismus MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
- MeSH
- chinazoliny aplikace a dávkování farmakologie terapeutické užití MeSH
- dospělí MeSH
- epidermální růstový faktor diagnostické užití genetika MeSH
- financování organizované MeSH
- lidé MeSH
- monoklonální protilátky aplikace a dávkování farmakologie terapeutické užití MeSH
- nádory prsu farmakoterapie genetika terapie MeSH
- retrospektivní studie MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- abstrakt z konference MeSH
