Predisposing factors of blood brain barrier penetration from docetaxel during lung cancer treatment: Preliminary study

Abstract

17102 Background: Patients with lung cancer account for approximately 50% of brain metastasis cases. On the other hand the majority of active cytotoxic agents (like taxanes) in lung cancer treatment, are unable to penetrate blood brain barrier (BBB) so the role of chemotherapy in management of brain metastasis from lung cancer remain controversial. To investigate predisposing factors (if any) of penetration of BBB from cytotoxic agents we measured concentation levels of Docetaxel in serum and cerebrospinal fluid (CSF) during first line chemotherapy. Methods: Twelve lung cancer patients receiving chemotherapy consisted of Docetaxel (100 mg/m2) and Carboplatin AUC 6 were included in this study. CSF and plasma samples were withdrawn half an hour after termination of chemotherapy infusion. Measurements were performed with high performance liquid chromatography and UV detection was at 227 nm. Results: Mean levels of docetaxel in blood was 2,5530 ± 0,53 mg/l and in CSF 0,7397 ± 0,22 mg/l. Three out of twelve patient had SCLC (2 with ED and 1 with LD) and 9 with NSCLC (2 stage IIIB and 7 stage IV). In three patients without metastasis no detectible level of docetaxel was measured. We were also unable to detect Docetaxel in CSF of the patient with NSCLC and metastasis in the ipsilateral lung. On the other hand in 9 patients with metastatic disease (4 brain metastasis 2 with bone metastasis 1 with metastasis in liver and adrenal and 2 with liver and bone metastasis) had detectable levels of docetaxel in CSF. There was not statistically significant correlation of docetaxel in plasma and CSF. Only one patient without any evidence of metastasis had a detectable level of Docetaxel in CSF (0,33229) but in 6 weeks a brain metastasis was apparent in brain MRI. Conclusions: Metastasis development seems to be associated with a modification of BBB penetration. If Docetaxel penetrates BBB (especially in the presence of brain metastasis) it would be probable to accelerate radiotherapy sensitivity of brain metastasis. No significant financial relationships to disclose.