التفاصيل البيبلوغرافية
| العنوان: |
Data from A Multicenter Phase I Trial of PX-866, an Oral Irreversible Phosphatidylinositol 3-Kinase Inhibitor, in Patients with Advanced Solid Tumors |
| المؤلفون: |
Antonio Jimeno, Razelle Kurzrock, Diana F. Hausman, Scott Peterson, S. Gail Eckhardt, Roy S. Herbst, Kevin Klucher, Alex C. H. Vo, Cindy L. O'Bryant, Goldy C. George, Wells A. Messersmith, Gerald S. Falchook, Daniel W. Bowles, David S. Hong |
| بيانات النشر: |
American Association for Cancer Research (AACR), 2023. |
| سنة النشر: |
2023 |
| الوصف: |
Purpose: The objectives of the study were to evaluate the maximum tolerated dose (MTD), safety, pharmacodynamics, pharmacokinetics, and antitumor activity of PX-866 in patients with incurable cancers.Experimental Design: This was a phase I, open-label, dose-escalation study. Drug was administered orally once per day either on an intermittent (arm 1; days 1–5 and 8–12 of a 28-day cycle) or continuous (arm 2; days 1–28 of a 28-day cycle) schedule. Additional patients were treated at the arm 2 MTD in a food effects substudy.Results: Eighty-four patients were treated in the arm 1 (n = 51), arm 2 (n = 20), and food effects (n = 13) cohorts. The most frequent study drug–related adverse events were gastrointestinal disorders (69.0%), with diarrhea being the most common (48.8%). The MTD was 12 and 8 mg for arm 1 and 2, respectively. The dose-limiting toxicities (DLT) consisted of grade III diarrhea (n = 3) and grade III elevated aspartate aminotransferase (AST; n = 1). The pharmacokinetics profile was dose proportional, with no evidence of drug accumulation. PX-866–associated inhibition of platelet pAKTSER473 was observed at the arm 2 MTD. The best response per Response Evaluation Criteria in Solid Tumors (RECIST) was stable disease in 22% of evaluable patients in arm 1, 53% in arm 2, and 11% in the food effects cohort. Eight patients were on study for 4 or more months.Conclusions: This first-in-human study shows that PX-866, an irreversible small-molecule inhibitor of phosphatidylinositol 3-kinase (PI3K), was well tolerated and was associated with prolonged stable disease, particularly when using a continuous dosing schedule. Clin Cancer Res; 18(15); 4173–82. ©2012 AACR. |
| URL الوصول: |
https://explore.openaire.eu/search/publication?articleId=doi_dedup___::55f392394cf359f81291540a0f4fb76f
https://doi.org/10.1158/1078-0432.c.6520830.v1 |
| حقوق: |
OPEN |
| رقم الأكسشن: |
edsair.doi.dedup.....55f392394cf359f81291540a0f4fb76f |
| قاعدة البيانات: |
OpenAIRE |
