A phase I trial of the oral cyclin dependent kinase inhibitor CYC202 in patients with advanced malignancy

摘要: 3042 Background: CYC202 is an oral cyclin dependent kinase inhibitor of CDKs-2, -7 and -9, leading to inhibition phosphorylation CDK substrates, cell cycle arrest, transcription induction apoptotsis. Preclinical studies show activity in lines xenografts. This trial determines the safety pharmacokinetics (PK) CYC202, given b.d. for 7 days q 21. Methods: A starting dose 200mg/day divided 2 doses was defined by a single preclinical toxicology. am pm with patient fasted hrs before after. PKs were performed on 1 1. Dose escalation occurred absence grade ≥3 toxicity DLT. Results: 21 patients enrolled (08/01–09/03) median age 62 (39–73 years), 6 F 15 M, WHO PS 2=2, 1=17 0=2. 42 cycles administered. We have reached 1600mg/day DLTs seen are 3 rash 4 hypokalaemia. Other toxicities include elevated creatinine (Cr) (rapidly reversible upon remova...