A phase 2 study of vorinostat in locally advanced, recurrent, or metastatic adenoid cystic carcinoma
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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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 0.001 |
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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".