التفاصيل البيبلوغرافية
| العنوان: |
Phase I study of BGT226, a pan-PI3K and mTOR inhibitor, in Japanese patients with advanced solid cancers. |
| المؤلفون: |
Minami, Hironobu1,2 (AUTHOR) hminami@med.kobe-u.ac.jp, Fujiwara, Yutaka1,2,3 (AUTHOR), Muro, Kei4 (AUTHOR), Sato, Masahiko5 (AUTHOR), Moriya, Atsuko5 (AUTHOR) |
| المصدر: |
Cancer Chemotherapy & Pharmacology. Aug2019, Vol. 84 Issue 2, p337-343. 7p. |
| مصطلحات موضوعية: |
*MTOR inhibitors, *CANCER, *SKIN tumors, *THERAPEUTICS, *PHARMACOKINETICS, *RESEARCH, *RESEARCH methodology, *EVALUATION research, *MEDICAL cooperation, *COMPARATIVE studies, *TUMORS, *CELL lines |
| مصطلحات جغرافية: |
JAPAN |
| مستخلص: |
The phosphatidylinositol 3-kinase (PI3K) pathway is a promising therapeutic target for various cancers. BGT226 is a pan-PI3K and mammalian target of rapamycin (mTOR) inhibitor. The tolerability and pharmacokinetics/pharmacodynamics of BGT226 were investigated in a phase I study in Japanese patients with advanced solid cancers. BGT226 was orally administered on days 1, 3, and 5 of each week. The initial dose of 10 mg was subsequently escalated to 20, 40, 80, and 100 mg in a cohort of three patients. Pharmacokinetics and pharmacodynamics were investigated using plasma, normal skin, and tumor samples. A total of 18 patients were enrolled and evaluated. The most frequently reported toxicities were diarrhea, nausea, decreased appetite, vomiting, and fatigue. They were all grade 1 or 2, and no dose-limiting toxicity was observed. However, all six patients treated at 100 mg experienced diarrhea and nausea, while two experienced a dose reduction and/or interruptions during the study. Two of five patients who exhibited stable disease continued the study treatment for ≥ 16 weeks. The absorption of BGT226 was rapid, and systemic exposure increased in a dose-dependent manner. Treatment with BGT226 did not change any of the biomarkers in neither normal skin nor tumor tissues. BGT226 was tolerated up to 100 mg three times a week in Japanese patients with solid cancers, without difference in toxicity profiles and pharmacokinetics compared to Western patients. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
Academic Search Index |
