With advanced cancer with multiple Anh Lengths to further evaluate its safety reps Opportunity and pharmacokinetic properties. The main objectives of this Phase I study of seliciclib orally twice t Possible for BMS 777607 7 days were administered every 21 days to the toxicity of t to establish profile of seliciclib, determine the dose limiting toxicity t of seliciclib, the recommended dose seliciclib determined in this schedule, to characterize the pharmacokinetic behavior of seliciclib document m possible and antitumor activity of t in patients with advanced solid tumors.
PATIENTS AND METHODS best patient selection Patients with histologically saturated diagnosis of a malignant solid tumors refractory r compared with conventional therapy was for treatment, provided they meet the following criteria: age X18 years, World Health Organization NVP-BKM120 PI3K inhibitor performance statusp2, business PROTECTED life expectancy of months, no prior cancer therapy within hematopoietic X3 4 weeks, no significant effects on gastrointestinal disease drug absorption, reasonable hours Ethics, liver and kidney function. The study was managed and controlled Controlled by the Office of Cancer Research UK drug development and led to good clinical practice in the H Pital Royal Marsden and the Beatson Oncology Centre. The protocol was developed by Cancer Research UK Central Institutional Review Board Protocol Review Committee and the Clinical Research Ethics Committees evaluated at the centers above. All patients gave written Einverst Ndniserkl Tion at baseline. Seliciclib treatment and dose escalation was provided by Cyclacel Ltd.
capsules of 50 mg and 200, stored at room temperature. The capsules were washed twice t Possible with the patient fasting 2 hours taken before and after drug administration. The patients were asked t Possible OSU-03012 write down the number of capsules taken, the time of admission and also when they had eaten last. Compliance was by Z Select the number of capsules assessed by the patient at the end of each treatment recycled. Patients were treated for the first cycle of treatment to the monitoring of the toxicity of t and PK sampling easier hospitalized. Subsequently End they were treated on an outpatient basis. The starting dose of seliciclib was selected on the basis of animal toxicology and PK experiments with a single dose study in patients over the dose range of 50 to 200 mg weight.
A dose of 400 mg was expected that significant plasma concentrations of pr To achieve clinical data on the pharmacokinetics of the base, and a human single-dose study showed that was the half-life of elimination twice for administration of t Possible, although inter-individual variability t of the clearance was high. It was decided, therefore, 100 mg orally twice t Possible for 7 days should start every 3 weeks may be administered. At least three patients were treated at each dose level. The dose ZUW CHSE were planned at least 100%, corresponding to significant drug toxicity T observed, and 40% thereafter. Dose-limiting toxicity of t is defined as drug toxicity T in the first round, including normal grade 4 neutropenia for 7 days or more, neutropenic fever, platelet count O25 109 L 1 and / or non-h Dermatological toxicityXgrade third This definition is closing t the nausea and vomiting, sp Ter reversible response to antiemetic therapy, grade 3-erh relationships Transaminases. The maximum tolerated dose was, in a dose below the DLT defined in more than