PMID- 26598548 OWN - NLM STAT- MEDLINE DCOM- 20161111 LR - 20200206 IS - 1569-8041 (Electronic) IS - 0923-7534 (Print) IS - 0923-7534 (Linking) VI - 27 IP - 2 DP - 2016 Feb TI - Phase II trial of dasatinib for recurrent or metastatic c-KIT expressing adenoid cystic carcinoma and for nonadenoid cystic malignant salivary tumors. PG - 318-23 LID - 10.1093/annonc/mdv537 [doi] AB - BACKGROUND: Adenoid cystic carcinoma (ACC) is a subtype of malignant salivary gland tumors (MSGT), in which 90% of cases express cKIT. Dasatinib is a potent and selective inhibitor of five oncogenic protein tyrosine kinases (PTKs)/kinase families including cKIT. We conducted a phase II study to determine the antitumor activity of dasatinib in ACC and non-ACC MSGT. PATIENTS AND METHODS: In a two-stage design, patients with progressive, recurrent/metastatic ACC (+cKIT) and non-ACC MSGT (separate cohort) were treated with dasatinib 70 mg p.o. b.i.d. Response was assessed every 8 weeks using RECIST. RESULTS: Of 54 patients: 40 ACC, 14 non-ACC (1, ineligible excluded); M:F = 28 : 26, median age 56 years (range 20-82 years), ECOG performance status 0 : 1 : 2 = 24 : 28 : 2, prior radiation: 44, prior chemotherapy: 21. The most frequent adverse events (AEs) (as % of patients, worst grade 2 or higher) were: fatigue (28%), nausea (19%), headache (15%), lymphopenia (7%), dyspnea (11%), alanine aminotransferase increased (7%), anorexia (7%), vomiting (7%), alkaline phosphatase increased (6%), diarrhea (6%), neutropenia (6%), and noncardiac chest pain (6%). No grade 4 AE occurred, 15 patients experienced a grade 3 AE, primarily dyspnea (5) and fatigue (4), and cardiac toxicity (1 prolonged QTc). Among ACC patients, best response to dasatinib: 1 patient (2.5%) had partial response, 20 patients (50%) had stable disease (SD) (3-14 months), 12 patients (30%) had PD, 2 withdrew, 3 discontinued therapy due to AE, and 2 died before cycle 2. Median progression-free survival was 4.8 months. Median overall survival was 14.5 months. For 14 assessable non-ACC patients, none had objective response, triggering early stopping rule. Seven had SD (range 1-7 months), 4 PD, 2 discontinued therapy due to AE, and 1 died before cycle 2. CONCLUSION: Although there was only one objective response, dasatinib is well tolerated, with tumor stabilization achieved by 50% of ACC patients. Dasatinib demonstrated no activity in non-ACC MSGT. CI - (c) The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com. FAU - Wong, S J AU - Wong SJ AD - Division of Hematology Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee swong@mcw.edu. FAU - Karrison, T AU - Karrison T AD - The University of Chicago, Chicago. FAU - Hayes, D N AU - Hayes DN AD - University of North Carolina at Chapel Hill, Chapel Hill. FAU - Kies, M S AU - Kies MS AD - Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston. FAU - Cullen, K J AU - Cullen KJ AD - University of Maryland Marlene and Stewart Greenebaum Cancer Center, Baltimore. FAU - Tanvetyanon, T AU - Tanvetyanon T AD - H. Lee Moffitt Cancer Center & Research Institute, Tampa, USA. FAU - Argiris, A AU - Argiris A AD - Department of Medical Oncology, Hygeia Hospital, Athens, Greece University of Texas Health Science Center at San Antonio, San Antonio. FAU - Takebe, N AU - Takebe N AD - Investigational Drug Branch, Cancer Therapy Evaluation Program, Rockville. FAU - Lim, D AU - Lim D AD - Department of Medicine, City of Hope, Duarte. FAU - Saba, N F AU - Saba NF AD - Winship Cancer Institute, Emory University, Atlanta. FAU - Worden, F P AU - Worden FP AD - Department of Medicine, University of Michigan Cancer Center, Ann Arbor. FAU - Gilbert, J AU - Gilbert J AD - Department of Hematology Oncology, Vanderbilt University, Nashville. FAU - Lenz, H J AU - Lenz HJ AD - USC Norris Comprehensive Cancer Center, Los Angeles. FAU - Razak, A R A AU - Razak AR AD - Department of Medical Oncology and Hematology, Princess Margaret Hospital, Toronto. FAU - Roberts, J D AU - Roberts JD AD - Massey Cancer Center, Richmond. FAU - Vokes, E E AU - Vokes EE AD - The University of Chicago, Chicago. FAU - Cohen, E E W AU - Cohen EE AD - University of California San Diego, Moores Cancer Center, San Diego, USA. LA - eng GR - P30 CA016672/CA/NCI NIH HHS/United States GR - N01-CM-62201/CM/NCI NIH HHS/United States PT - Clinical Trial, Phase II PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20151123 PL - England TA - Ann Oncol JT - Annals of oncology : official journal of the European Society for Medical Oncology JID - 9007735 RN - 0 (Antineoplastic Agents) RN - 0 (Protein Kinase Inhibitors) RN - EC 2.7.10.1 (Proto-Oncogene Proteins c-kit) RN - RBZ1571X5H (Dasatinib) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Antineoplastic Agents/adverse effects/*therapeutic use MH - Carcinoma, Adenoid Cystic/*drug therapy/pathology MH - Dasatinib/adverse effects/*therapeutic use MH - Disease-Free Survival MH - Female MH - Humans MH - Male MH - Middle Aged MH - Neoplasm Recurrence, Local/*drug therapy/pathology MH - Protein Kinase Inhibitors/adverse effects/*therapeutic use MH - Proto-Oncogene Proteins c-kit/*antagonists & inhibitors/metabolism MH - Salivary Gland Neoplasms/*drug therapy/pathology MH - Treatment Outcome MH - Young Adult PMC - PMC4722891 OTO - NOTNLM OT - adenoid cystic carcinoma OT - cKIT OT - dasatinib OT - malignant salivary gland cancer OT - phase II EDAT- 2015/11/26 06:00 MHDA- 2016/11/12 06:00 PMCR- 2017/02/01 CRDT- 2015/11/25 06:00 PHST- 2015/07/26 00:00 [received] PHST- 2015/10/26 00:00 [accepted] PHST- 2015/11/25 06:00 [entrez] PHST- 2015/11/26 06:00 [pubmed] PHST- 2016/11/12 06:00 [medline] PHST- 2017/02/01 00:00 [pmc-release] AID - S0923-7534(19)35540-1 [pii] AID - mdv537 [pii] AID - 10.1093/annonc/mdv537 [doi] PST - ppublish SO - Ann Oncol. 2016 Feb;27(2):318-23. doi: 10.1093/annonc/mdv537. Epub 2015 Nov 23.