A phase I trial of ispinesib, a kinesin spindle protein inhibitor, with docetaxel in patients with advanced solid tumours.

摘要: The aim of this study is to define the maximum tolerated dose (MTD), safety, pharmacokinetics (PKs) and efficacy ispinesib (SB-715992) in combination with docetaxel. Patients advanced solid tumours were treated (6-12 mg m(-2)) docetaxel (50-75 m(-2)). Docetaxel was administered over 1 h followed by a 1-h infusion on day 21-day schedule. At least three patients at each level. Blood samples collected during cycle for PK analysis. Clinical response assessments performed every two cycles using RECIST guidelines. Twenty-four four levels. Prolonged neutropaenia febrile limiting six patients, respectively. MTD 10 m(-2) 60 m(-2). Pharmacokinetic assessment demonstrated concentrations docetaxel, consistent published data from single agent studies drugs. Seven (six hormone refractory prostate cancer (HRPC), one renal cancer) had best stable disease (>or=18 weeks). One patient HRPC confirmed >50% prostatic-specific antigen decrease. defined an acceptable toxicity profile. Preliminary suggest no interaction between