دورية أكاديمية
A phase II trial of all-trans retinoic acid (ATRA) in advanced adenoid cystic carcinoma.
| العنوان: | A phase II trial of all-trans retinoic acid (ATRA) in advanced adenoid cystic carcinoma. |
|---|---|
| المؤلفون: | Hanna GJ; Department of Medical Oncology, Center for Head & Neck Oncology, Center for Salivary and Rare Head and Neck Cancers, Dana-Farber Cancer Institute, Boston, USA. Electronic address: glenn_hanna@dfci.harvard.edu., ONeill A; Department of Data Science, Dana-Farber Cancer Institute, Boston, USA., Cutler JM; Department of Medical Oncology, Center for Head & Neck Oncology, Center for Salivary and Rare Head and Neck Cancers, Dana-Farber Cancer Institute, Boston, USA., Flynn M; Department of Medical Oncology, Center for Head & Neck Oncology, Center for Salivary and Rare Head and Neck Cancers, Dana-Farber Cancer Institute, Boston, USA., Vijaykumar T; Center for Hematologic Oncology, Dana-Farber Cancer Institute, Boston, USA., Clark JR; Center for Head and Neck Cancers, Massachusetts General Hospital, Boston, USA., Wirth LJ; Center for Head and Neck Cancers, Massachusetts General Hospital, Boston, USA., Lorch JH; Department of Medical Oncology, Center for Head & Neck Oncology, Center for Salivary and Rare Head and Neck Cancers, Dana-Farber Cancer Institute, Boston, USA., Park JC; Center for Head and Neck Cancers, Massachusetts General Hospital, Boston, USA., Mito JK; Department of Pathology, Brigham & Women's Hospital, Boston, USA., Lohr JG; Center for Hematologic Oncology, Dana-Farber Cancer Institute, Boston, USA., Kaufman J; Adenoid Cystic Carcinoma Research Foundation, USA., Burr NS; Adenoid Cystic Carcinoma Research Foundation, USA., Zon LI; Department of Stem Cell and Regenerative Biology, Boston Children's Hospital and Harvard Medical School, Boston, USA., Haddad RI; Department of Medical Oncology, Center for Head & Neck Oncology, Center for Salivary and Rare Head and Neck Cancers, Dana-Farber Cancer Institute, Boston, USA. |
| المصدر: | Oral oncology [Oral Oncol] 2021 Aug; Vol. 119, pp. 105366. Date of Electronic Publication: 2021 Jun 03. |
| نوع المنشور: | Clinical Trial, Phase II; Journal Article; Research Support, N.I.H., Extramural |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: England NLM ID: 9709118 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0593 (Electronic) Linking ISSN: 13688375 NLM ISO Abbreviation: Oral Oncol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Amsterdam : Elsevier Original Publication: Oxford ; New York : Pergamon, c1997- |
| مواضيع طبية MeSH: | Carcinoma, Adenoid Cystic*/drug therapy, Tretinoin/*therapeutic use, Antineoplastic Combined Chemotherapy Protocols ; Humans ; Neoplasm Recurrence, Local/drug therapy ; Phosphatidylinositol 3-Kinases ; Treatment Outcome |
| مستخلص: | Background: Effective therapies are lacking for recurrent, metastatic adenoid cystic carcinoma (R/M ACC) and preclinical models suggest retinoic acid agonists inhibit ACC growth. This phase II trial evaluated all-trans retinoic acid (ATRA) as a novel therapy for ACC. Methods: Patients with R/M ACC (any site) with clinical and/or radiographic progression ≤12 months prior to study entry were eligible. Cohort 1 (CH1) received ATRA 45 mg/m 2 split oral daily dosing on days 1-14 of a 28-day cycle; Cohort 2 (CH2) received the same dosing continuously. Primary endpoint was best overall response rate (CR + PR) (RECIST v1.1). Secondary endpoints: safety and progression-free survival (PFS). Exploratory analyses: ATRA impact on MYB expression and genomic predictors of response. Results: Eighteen patients enrolled. There were no responses, but 61% (11/18) had stable disease (SD) and 28% (5/18) progression as best response; 11% (2/18) unevaluable. Median duration of stability: 3.7 months (95%CI, 1.9-3.9). One patient (CH1) remains on drug with SD approaching 1 year. Half of those who received prior VEGFR therapy achieved SD (4/8). At median follow up of 7.9 months, median PFS was 3.2 months (95%CI, 1.8-3.9). N = 1 required dose adjustment; N = 1 came off drug for toxicity. There were no grade 3-4 adverse events. NOTCH1 and PI3K pathway alterations were most frequent. Low MYB protein expression was associated with longer duration of stability on ATRA (P < 0.01). Conclusion(s): While the trial did not meet its prespecified response endpoint, ATRA alone or in combination may be a low toxicity treatment for disease growth stabilization in R/M ACC. (Copyright © 2021 Elsevier Ltd. All rights reserved.) |
| فهرسة مساهمة: | Keywords: ACC; ATRA; Head and neck cancer; Retinoic acid; Salivary cancer; Targeted therapy |
| المشرفين على المادة: | 5688UTC01R (Tretinoin) |
| تواريخ الأحداث: | Date Created: 20210606 Date Completed: 20220201 Latest Revision: 20220201 |
| رمز التحديث: | 20221213 |
| DOI: | 10.1016/j.oraloncology.2021.105366 |
| PMID: | 34091189 |
| قاعدة البيانات: | MEDLINE |
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