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Ann Oncol. 2016 Feb;27(2):318-23. doi: 10.1093/annonc/mdv537. Epub 2015 Nov 23.

Phase II trial of dasatinib for recurrent or metastatic c-KIT expressing adenoid cystic carcinoma and for nonadenoid cystic malignant salivary tumors.

Author information

1
Division of Hematology Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee swong@mcw.edu.
2
The University of Chicago, Chicago.
3
University of North Carolina at Chapel Hill, Chapel Hill.
4
Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston.
5
University of Maryland Marlene and Stewart Greenebaum Cancer Center, Baltimore.
6
H. Lee Moffitt Cancer Center & Research Institute, Tampa, USA.
7
Department of Medical Oncology, Hygeia Hospital, Athens, Greece University of Texas Health Science Center at San Antonio, San Antonio.
8
Investigational Drug Branch, Cancer Therapy Evaluation Program, Rockville.
9
Department of Medicine, City of Hope, Duarte.
10
Winship Cancer Institute, Emory University, Atlanta.
11
Department of Medicine, University of Michigan Cancer Center, Ann Arbor.
12
Department of Hematology Oncology, Vanderbilt University, Nashville.
13
USC Norris Comprehensive Cancer Center, Los Angeles.
14
Department of Medical Oncology and Hematology, Princess Margaret Hospital, Toronto.
15
Massey Cancer Center, Richmond.
16
University of California San Diego, Moores Cancer Center, San Diego, USA.

Abstract

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.

KEYWORDS:

adenoid cystic carcinoma; cKIT; dasatinib; malignant salivary gland cancer; phase II

PMID:
26598548
PMCID:
PMC4722891
DOI:
10.1093/annonc/mdv537
[Indexed for MEDLINE]
Free PMC Article

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