دورية أكاديمية
Phase I Study of Glesatinib (MGCD265) in Combination with Erlotinib or Docetaxel in Patients with Advanced Solid Tumors
| العنوان: | Phase I Study of Glesatinib (MGCD265) in Combination with Erlotinib or Docetaxel in Patients with Advanced Solid Tumors |
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| المؤلفون: | Patnaik, Amita, Gadgeel, Shirish M, Papadopoulos, Kyriakos P, Rasco, Drew W, Haas, Naomi B, Der-Torossian, Hirak, Faltaos, Demiana, Potvin, Diane, Tassell, Vanessa, Tawashi, Manal, Chao, Richard, O'Dwyer, Peter J |
| المصدر: | Hematology/Oncology Articles |
| بيانات النشر: | Henry Ford Health Scholarly Commons |
| سنة النشر: | 2022 |
| المجموعة: | Henry Ford Health System Scholarly Commons |
| مصطلحات موضوعية: | Antineoplastic Combined Chemotherapy Protocols, Benzeneacetamides, Docetaxel, Erlotinib Hydrochloride, Humans, Maximum Tolerated Dose, Neoplasms, Pyridines |
| الوصف: | BACKGROUND: Oncogenic drivers in solid tumors include aberrant activation of mesenchymal epithelial transition factor (MET) and AXL. OBJECTIVE: This study investigated the safety and antitumor activity of glesatinib, a multitargeted receptor tyrosine kinase inhibitor that inhibits MET and AXL at clinically relevant doses, in combination with erlotinib or docetaxel. PATIENTS AND METHODS: The phase I portion of this open-label, multicenter study included two parallel arms in which ascending doses of oral glesatinib (starting dose 96 mg/m(2)) were administered with erlotinib or docetaxel (starting doses 100 mg once daily and 50 mg/m(2), respectively) using a modified 3 + 3 design. Maximum tolerated dose (MTD) was based on dose-limiting toxicities (DLTs) during the first 21-day treatment cycle. Enrollment focused on patients with solid tumor types typically associated with MET aberration and/or AXL overexpression. The primary objective was to determine the safety profile of the treatment combinations. Antitumor activity and pharmacokinetics (PK) were also assessed. RESULTS: Ten dose levels of glesatinib across three glycolate formulations (unmicronized, micronized, or micronized version 2 [V2] tablets) available during the course of the study were investigated in 14 dose-escalation cohorts (n = 126). MTDs of unmicronized glesatinib plus erlotinib or docetaxel, and micronized glesatinib plus erlotinib were not reached. Micronized glesatinib 96 mg/m(2) plus docetaxel exceeded the MTD. Further dosing focused on glesatinib micronized V2: maximum administered dose (MAD) was 700 mg twice daily with erlotinib 150 mg once daily or docetaxel 75 mg/m(2) every 3 weeks. DLTs, acceptable at lower glesatinib (micronized V2) dose levels, occurred in two of five and two of six patients at the MADs of glesatinib + erlotinib and glesatinib + docetaxel, respectively. Across all cohorts, the most frequent treatment-related adverse events were diarrhea (glesatinib + erlotinib: 84.1%; glesatinib + docetaxel: 45.6%), fatigue (46.4%, ... |
| نوع الوثيقة: | text |
| وصف الملف: | application/pdf |
| اللغة: | unknown |
| العلاقة: | https://scholarlycommons.henryford.com/hematologyoncology_articles/234Test; http://sfxhosted.exlibrisgroup.com/hfhs?sid=Entrez:PubMed&id=pmid:35347559Test |
| الإتاحة: | https://scholarlycommons.henryford.com/hematologyoncology_articles/234Test http://sfxhosted.exlibrisgroup.com/hfhs?sid=Entrez:PubMed&id=pmid:35347559Test |
| رقم الانضمام: | edsbas.7C37FFF6 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |