A Phase I Clinical and Pharmacokinetic Study of Oral CI-1033 in Combination with Docetaxel in Patients with Advanced Solid Tumors

摘要: Purpose: CI-1033 is an orally available 4-anilinoquinazolone irreversible tyrosine kinase inhibitor of erbB-1, erbB-2, and erbB-4. We conducted a dose escalation study with docetaxel to assess the safety profile pharmacokinetics combination establish maximum tolerated dose. Experimental Design: Twenty-six patients advanced solid tumors were treated on four dosing cohorts starting at (50 mg/d) + (75 mg/m2). An intermittent schedule avoided concurrent drug dosing. Results: alone was escalated from 50 75 mg/d (dose level 2), where diarrhea limiting; 38% incidence cycle 1 febrile neutropenia prompted de-escalation both for 3, dose-limiting toxicities further 45 mg/d. Given equivalent profiles [CI-1033 mg/m2)] 4 (45 (60 mg/m2)], former determined be recommended phase II dose, given greater intensity drugs. Antitumor activity noted in three patients, including complete response patient cervix uteri cancer. Pharmacokinetic analysis showed possible effect pharmacokinetics. Conclusions: It feasible combine pan-erbB cancer patients. established combination. Further investigation this should include rigorous pharmacokinetics.