A phase 2 study of vorinostat in locally advanced, recurrent, or metastatic adenoid cystic carcinoma
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Bibliographic record
Abstract
// Priscila H. Goncalves 1 , Lance K. Heilbrun 1 , Michael T. Barrett 2 , Shivaani Kummar 4, 8 , Aaron R. Hansen 3 , Lillian L. Siu 3 , Richard L. Piekarz 4 , Ammar W. Sukari 1 , Joseph Chao 5 , Mary Jo Pilat 1, 6 , Daryn W. Smith 1 , Lindsay Casetta 1 , Scott A. Boerner 1, 7 , Alice Chen 4 , Elizabeth Lenkiewicz 2 , Smriti Malasi 2 , Patricia M. LoRusso 1, 7 1 Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA 2 Mayo Clinic Arizona, Scottsdale, AZ, USA 3 Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada 4 Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD, USA 5 Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, CA, USA 6 Eugene Applebaum College of Pharmacy and Health Sciences, Physician Assistant Studies, Wayne State University, Detroit, MI, USA 7 Current address: Yale Cancer Center, New Haven, CT, USA 8 Current address: Stanford University, Palo Alto, CA, USA Correspondence to: Priscila H. Goncalves, email: priscila.goncalves@nih.gov Keywords: adenoid cystic, salivary gland tumor, vorinostat, suberoylanilide hydroxamic acid, SAHA Received: February 09, 2017 Accepted: March 14, 2017 Published: March 22, 2017 ABSTRACT Purpose: Vorinostat is a histone deacetylase inhibitor (HDACi). Based on a confirmed partial response (PR) in an adenoid cystic carcinoma (ACC) patient treated with vorinostat in a prior phase 1 trial, we initiated this phase 2 trial. Methods: Vorinostat was administered orally 400 mg daily, 28 day cycles. The primary objective was to evaluate response rate (RR). Exploratory studies included whole exome sequencing (WES) of selected patients. Results: Thirty patients were enrolled. Median age of patients was 53 years (range 21–73). Median number of cycles was 5 (range 1-66). Lymphopenia ( n = 5), hypertension ( n = 3), oral pain ( n = 2), thromboembolic events ( n = 2) and fatigue ( n = 2) were the only grade 3 adverse events (AEs) that occurred in more than 1 patient. Eleven patients were dose reduced secondary to drug-related AEs. Two patients had a partial response (PR), with response durations of 53 and 7.2 months. One patient had a minor response with a decrease in ascites (for 19 cycles). Stable disease was the best response in 27 patients. Targeted and WES of 8 patients in this trial identified mutations in chromatin remodeling genes highlighting the role of the epigenome in ACC. Conclusion: Vorinostat demonstrated efficacy in patients with ACC supporting the inclusion of HDACi in future studies to treat ACC.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it