Phase 1 Studies of Poziotinib, an Irreversible Pan-HER Tyrosine Kinase Inhibitor in Patients with Advanced Solid Tumors / Journal of the Korean Cancer Association, 대한암학회지
Cancer Research and Treatment
; : 835-842, 2018.
Article
in En
| WPRIM
| ID: wpr-715974
Responsible library:
WPRO
ABSTRACT
PURPOSE:
Poziotinib, a pan-human epidermal growth factor receptor 2 (HER) tyrosine kinase inhibitor, has shown potent activity againstwild type of epidermal growth factorreceptor(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 ANDMETHODS:
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 eventswere 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.Key words
Full text:
1
Database:
WPRIM
Main subject:
Appointments and Schedules
/
Phosphotransferases
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Pruritus
/
Stomach Neoplasms
/
Stomatitis
/
Tyrosine
/
In Vitro Techniques
/
Protein-Tyrosine Kinases
/
Breast Neoplasms
/
Pharmacokinetics
Type of study:
Etiology_studies
/
Incidence_studies
/
Observational_studies
/
Risk_factors_studies
Limits:
Humans
Language:
En
Journal:
Cancer Research and Treatment
Year:
2018
Document type:
Article