Phase II study of lapatinib in recurrent or metastatic epidermal growth factor receptor and/or erbB2 expressing adenoid cystic carcinoma and non-adenoid cystic carcinoma malignant tumors of the salivary glands

被引:212
作者
Agulnik, Mark
Cohen, Ezra W. E.
Cohen, Roger B.
Chen, Eric X.
Vokes, Everett E.
Hotte, Sebastien J.
Winquist, Eric
Laurie, Scott
Hayes, D. Neil
Dancey, Janet E.
Brown, Shirley
Pond, Gregory R.
Lorimer, Ian
Daneshmand, Manijeh
Ho, James
Tsao, Ming-Sound
Siu, Lillian L.
机构
[1] Princess Margaret Hosp, Phase II Consortium, Toronto, ON M4X 1K9, Canada
[2] Univ Chicago, Dept Med, Hematol Oncol Sect, Chicago, IL 60637 USA
[3] Univ N Carolina, Chapel Hill, NC USA
[4] Natl Canc Inst, Bethesda, MD USA
关键词
D O I
10.1200/JCO.2007.11.8612
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose Expression of erbB2 and/or epidermal growth factor receptor (EGFR) is associated with biologic aggressiveness and poor prognosis in malignant salivary gland tumors (MSGTs). This phase II study was conducted to determine the antitumor activity of lapatinib, a dual inhibitor of EGFR and erbB2 tyrosine kinase activity, in MSGTs. Patients and Methods Patients with progressive, recurrent, or metastatic adenoid cystic carcinoma (ACC) immunohistochemically expressing at least 1 + EGFR and/or 2 + erbB2 were treated with lapatinib 1,500 mg daily, in a two-stage cohort. Patients with non-ACC MSGTs were treated as a separate single-stage cohort. Results Of 62 patients screened, 29 of 33 (88%) ACC and 28 of 29 (97%) non-ACC patients expressed EGFR and/or erbB2. Forty patients with progressive disease were enrolled onto the study. Among 19 assessable ACC patients, there were no objective responses, 15 patients (79%) had stable disease (SD), nine patients (47%) had SD >= 6 months, and four patients (21%) had progressive disease (PD). For 17 assessable non-ACC patients, there were no objective responses, eight patients (47%) had SD, four patients (24%) had SD >= 6 months, and nine patients (53%) had PD. The most frequent adverse events were grade 1 to 2 diarrhea, fatigue, and rash. Eight paired tumor biopsies for correlative studies were procured; results did not correlate with clinical outcome. Conclusion Although no responses were observed, lapatinib was well tolerated, with prolonged tumor stabilization of >= 6 months in 36% (95% CI, 21% to 54%) of assessable patients. The antitumor effects of lapatinib in MGSTs appear mainly cytostatic, hence evaluation of other molecular targeted agents, or combinations with lapatinib, may be considered. Continued efforts should be made to gain better understanding into the biology of this heterogeneous group of malignancies.
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页码:3978 / 3984
页数:7
相关论文
共 45 条
[11]   Imatinib mesylate can induce objective response in progressing, highly expressing KIT adenoid cystic carcinoma of the salivary glands [J].
Faivre, S ;
Raymond, E ;
Casiraghi, O ;
Temam, S ;
Berthaud, P .
JOURNAL OF CLINICAL ONCOLOGY, 2005, 23 (25) :6271-6273
[12]   Expression of androgen receptor, epidermal growth factor receptor, and transforming growth factor α in salivary duct carcinoma [J].
Fan, CY ;
Melhem, MF ;
Hosal, AS ;
Grandis, JR ;
Barnes, EL .
ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY, 2001, 127 (09) :1075-1079
[13]   Prognostic significance of biomarkers (c-erbB-2, p53, proliferating cell nuclear antigen, and DNA content) in salivary duct carcinoma [J].
Felix, A ;
ElNaggar, AK ;
Press, MF ;
Ordonez, NG ;
Fonseca, I ;
Tucker, SL ;
Luna, MA ;
Batsakis, JG .
HUMAN PATHOLOGY, 1996, 27 (06) :561-566
[14]   C-ERBB-2/NEU ONCOGENE AND KI-67 ANALYSIS IN THE ASSESSMENT OF PALATAL SALIVARY-GLAND NEOPLASMS [J].
GIANNONI, C ;
ELNAGGAR, AK ;
ORDONEZ, NG ;
TU, ZN ;
AUSTIN, J ;
LUNA, MA ;
BATSAKIS, JG .
OTOLARYNGOLOGY-HEAD AND NECK SURGERY, 1995, 112 (03) :391-398
[15]   HER2 expression in salivary gland carcinomas: Dependence on histological subtype [J].
Glisson, B ;
Colevas, AD ;
Haddad, R ;
Krane, J ;
El-Naggar, A ;
Kies, M ;
Costello, R ;
Summey, C ;
Arquette, M ;
Langer, C ;
Amrein, PC ;
Posner, M .
CLINICAL CANCER RESEARCH, 2004, 10 (03) :944-946
[16]  
Glisson BS, 2005, J CLIN ONCOL, V23, p508S
[17]   Levels of TGF-α and EGFR protein in head and neck squamous cell carcinoma and patient survival [J].
Grandis, JR ;
Melhem, MF ;
Gooding, WE ;
Day, R ;
Holst, VA ;
Wagener, MM ;
Drenning, SD ;
Tweardy, DJ .
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1998, 90 (11) :824-832
[18]   Herceptin in patients with advanced or metastatic salivary gland carcinomas. A phase II study [J].
Haddad, R ;
Colevas, AD ;
Krane, JF ;
Cooper, D ;
Glisson, B ;
Amrein, PC ;
Weeks, L ;
Costello, R ;
Posner, M .
ORAL ONCOLOGY, 2003, 39 (07) :724-727
[19]   Prognostic factors in major salivary gland cancer [J].
Hocwald, E ;
Korkmaz, H ;
Yoo, GH ;
Adsay, V ;
Shibuya, TY ;
Abrams, J ;
Jacobs, JR .
LARYNGOSCOPE, 2001, 111 (08) :1434-1439
[20]   Imatinib mesylate in patients with adenoid cystic cancers of the salivary glands expressing c-kit: A Princess Margaret Hospital phase II consortium study [J].
Hotte, SJ ;
Winquist, EW ;
Lamont, E ;
MacKenzie, M ;
Vokes, E ;
Chen, EX ;
Brown, S ;
Pond, GR ;
Murgo, A ;
Siu, LL .
JOURNAL OF CLINICAL ONCOLOGY, 2005, 23 (03) :585-590