A phase I study of TPI 287 concurrent with fractionated stereotactic radiotherapy (FSRT) in treatment of brain metastases from advanced breast and non-small cell lung cancer (NSCLC).

TPS2076 Background: TPI 287, a member of taxanes diterpenoid (taxoid) family, is a microtubule-inhibitor with significant cytotoxic activity. TPI 287 is not a P-glycoprotein substrate and therefore is able to circumvent resistance associated with the expression of the multidrug-resistance-1 (MDR-1) gene. Preclinical studies have demonstrated that TPI 287 crosses the blood brain barrier and reaches a therapeutic concentration in brain tissue. In vivo models of human breast cancer brain metastasis show that TPI 287 significantly reduces the formation of large brain metastases. The radiosensitizing effect of taxanes is well established. This report describes an ongoing phase I trial of TPI 287 concurrent with FSRT in patients (pts) with 1-3 brain metastases from histologically or cytologically confirmed advanced breast or NSCL cancer. Methods: This phase I study employs a standard 3 + 3 dose escalation design exploring 6 sequential dose escalation cohorts (NCT02187822). Pts with up to 3 untreated brain metas...