S-Space College of Medicine/School of Medicine (의과대학/대학원) Internal Medicine (내과학전공) Journal Papers (저널논문_내과학전공)
Phase 1 studies of poziotinib, an irreversible pan-her tyrosine kinase inhibitor in patients with advanced solid tumors
- Kim, Tae Min; Lee, Keun-Wook; Oh, Do-Youn; Lee, Jong-Seok; Im, Seock-Ah; Kim, Dong-Wan; Han, Sae-Won; Kim, Yu Jung; Kim, Tae-You; Kim, Jee Hyun; Han, Hyesun; Kim, Woo Ho; Bang, Yung-Jue
- Issue Date
- Cancer Research and Treatment, Vol.50 No.3, pp.835-842
- Purpose Poziotinib, a pan-human epidermal growth factor receptor 2 (HER) tyrosine kinase inhibitor, has shown potent activity against wild type of epidermal growth factor receptor (EGFR) family kinases including EGFR, HER2, and HER4 and EGFR-mutant cells in vitro. Two phase I studies were conducted to determine the maximum tolerated dose (MTD), pharmacokinetics, safety, and antitumor activity against advanced solid tumors. Materials and Methods Standard 3+3 dose escalation scheme using two different dosing schedules were studied: once daily, 14-day on, and 7-day off (intermittent schedule); and once daily continuous dosing with food effect. Additional patients were enrolled in an expansion cohort. Results A total of 75 patients were enrolled in the two studies. The most common drug-related treatment-emergent adverse events were diarrhea, rash, stomatitis, pruritus, and anorexia. Dose-limiting toxicities were grade 3 diarrhea in the intermittent schedule and grade 3 anorexia and diarrhea in the continuous dosing schedule. The MTDs were determined as 24 mg/day in the intermittent dosing schedule and 18 mg/day in the continuous dosing schedule. Eight (16%) and 24 (47%) of 51 evaluable patients in the intermittent schedule achieved partial response (PR) and stable disease (SD), respectively. Four (21%) and six (32%) of 19 evaluable patients in continuous dosing schedule achieved PR and SD, respectively. Patients with PR (n=7) or SD. 12 weeks (n=7) had HER2 amplification (n=7; breast cancer, 5; and stomach cancer, 2) and EGFR amplification (n=1, squamous cell lung cancer). Conclusion Poziotinib was safe and well tolerated in patients with advanced solid tumors. It showed an encouraging activity against EGFR-mutant and HER2-amplified cancers.