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 > or = 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 > or = 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 > or = 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.
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 > or = 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 > or = 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 > or = 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.
Authors: M Pia Morelli; Emiliano Calvo; Esther Ordoñez; Michael J Wick; Belen-Rubio Viqueira; Pedro P Lopez-Casas; Elizabeth Bruckheimer; Antonio Calles-Blanco; David Sidransky; Manuel Hidalgo Journal: J Clin Oncol Date: 2011-12-19 Impact factor: 44.544
Authors: Naresh Jegadeesh; Yuan Liu; Roshan S Prabhu; Kelly R Magliocca; David M Marcus; Kristin A Higgins; Jeffrey M Vainshtein; J Trad Wadsworth; Jonathan J Beitler Journal: Oral Oncol Date: 2015-05-29 Impact factor: 5.337
Authors: John A Jakob; Merrill S Kies; Bonnie S Glisson; Michael E Kupferman; Diane D Liu; J Jack Lee; Adel K El-Naggar; Ana M Gonzalez-Angulo; George R Blumenschein Journal: Head Neck Date: 2015-03-30 Impact factor: 3.147
Authors: Tobias Ach; Katharina Zeitler; Stephan Schwarz-Furlan; Katharina Baader; Abbas Agaimy; Christian Rohrmeier; Johannes Zenk; Martin Gosau; Torsten E Reichert; Gero Brockhoff; Tobias Ettl Journal: Virchows Arch Date: 2012-12-15 Impact factor: 4.064
Authors: Chun-ling Dai; Amit K Tiwari; Chung-Pu Wu; Xiao-Dong Su; Si-Rong Wang; Dong-geng Liu; Charles R Ashby; Yan Huang; Robert W Robey; Yong-ju Liang; Li-ming Chen; Cheng-Jun Shi; Suresh V Ambudkar; Zhe-Sheng Chen; Li-wu Fu Journal: Cancer Res Date: 2008-10-01 Impact factor: 12.701
Authors: Ricardo S Macarenco; Timothy S Uphoff; Heather Flynn Gilmer; Robert B Jenkins; Stephen N Thibodeau; Jean E Lewis; Julian R Molina; Ping Yang; Marie-Christine Aubry Journal: Mod Pathol Date: 2008-06-27 Impact factor: 7.842