TY - JOUR
T1 - Sunitinib plus erlotinib for the treatment of advanced/metastatic non-small-cell lung cancer
T2 - A lead-in study
AU - Blumenschein, George R.
AU - Ciuleanu, Tudor
AU - Robert, Francisco
AU - Groen, Harry J.M.
AU - Usari, Tiziana
AU - Ruiz-Garcia, Ana
AU - Tye, Lesley
AU - Chao, Richard C.
AU - Juhasz, Erzsebet
N1 - Funding Information:
Medical writing/editorial support was provided by Siân Marshall at ACUMED (Tytherington, United Kingdom) with funding from Pfizer Inc. This study was sponsored by Pfizer Inc.
PY - 2012/9
Y1 - 2012/9
N2 - BACKGROUND:: This randomized, double-blind, multicenter study evaluated sunitinib plus erlotinib versus placebo plus erlotinib. Subjects with advanced non-small-cell lung cancer had received prior treatment with a platinum-based regimen. Here, we report safety, pharmacokinetics, and antitumor activity of the combination of sunitinib and erlotinib. METHODS:: Lead-in subjects in this phase II study received sunitinib 37.5 mg/d and erlotinib 150 mg/d. Safety, including dose-limiting toxicities (DLTs, cohort 1 only), pharmacokinetic profiles, and antitumor activity were investigated (cohorts 1 and 2). RESULTS:: Thirty patients were evaluated. The combination of sunitinib and erlotinib was tolerable. Diarrhea (76.9%), fatigue (61.5%), and decreased appetite (53.8%) were the most frequent adverse events in cohort 1; and diarrhea (52.9%) and rash (41.2%) were the most frequent adverse events in cohort 2. DLTs were observed (fatigue, n = 2 and paronychial inflammation, n = 1) in three of 13 patients evaluated for DLTs. Geometric mean ratios for the maximum plasma concentration (Cmax) and area under plasma concentration-time profile from time 0 to 24 hours of erlotinib with and without sunitinib were 1.05 and 1.03, respectively. Corresponding values for sunitinib with and without erlotinib were 0.62 and 0.62 for sunitinib, 2.13 and 2.07 for SU12662; and 0.81 and 0.79 for total drug. Three patients experienced partial response as per response evaluation criteria in solid tumor. CONCLUSION:: A dosage of sunitinib 37.5 mg/d concurrently with erlotinib 150 mg/d was tolerable and established the recommended combinatorial dose in subjects with platinum-refractory non-small-cell lung cancer. Coadministration of sunitinib with erlotinib does not affect the pharmacokinetics of erlotinib, but may result in decreased exposure to sunitinib.
AB - BACKGROUND:: This randomized, double-blind, multicenter study evaluated sunitinib plus erlotinib versus placebo plus erlotinib. Subjects with advanced non-small-cell lung cancer had received prior treatment with a platinum-based regimen. Here, we report safety, pharmacokinetics, and antitumor activity of the combination of sunitinib and erlotinib. METHODS:: Lead-in subjects in this phase II study received sunitinib 37.5 mg/d and erlotinib 150 mg/d. Safety, including dose-limiting toxicities (DLTs, cohort 1 only), pharmacokinetic profiles, and antitumor activity were investigated (cohorts 1 and 2). RESULTS:: Thirty patients were evaluated. The combination of sunitinib and erlotinib was tolerable. Diarrhea (76.9%), fatigue (61.5%), and decreased appetite (53.8%) were the most frequent adverse events in cohort 1; and diarrhea (52.9%) and rash (41.2%) were the most frequent adverse events in cohort 2. DLTs were observed (fatigue, n = 2 and paronychial inflammation, n = 1) in three of 13 patients evaluated for DLTs. Geometric mean ratios for the maximum plasma concentration (Cmax) and area under plasma concentration-time profile from time 0 to 24 hours of erlotinib with and without sunitinib were 1.05 and 1.03, respectively. Corresponding values for sunitinib with and without erlotinib were 0.62 and 0.62 for sunitinib, 2.13 and 2.07 for SU12662; and 0.81 and 0.79 for total drug. Three patients experienced partial response as per response evaluation criteria in solid tumor. CONCLUSION:: A dosage of sunitinib 37.5 mg/d concurrently with erlotinib 150 mg/d was tolerable and established the recommended combinatorial dose in subjects with platinum-refractory non-small-cell lung cancer. Coadministration of sunitinib with erlotinib does not affect the pharmacokinetics of erlotinib, but may result in decreased exposure to sunitinib.
KW - Erlotinib
KW - Non-small-cell lung cancer
KW - Pharmacokinetics
KW - Safety
KW - Sunitinib
UR - http://www.scopus.com/inward/record.url?scp=84865690782&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84865690782&partnerID=8YFLogxK
U2 - 10.1097/JTO.0b013e31825cca1c
DO - 10.1097/JTO.0b013e31825cca1c
M3 - Article
C2 - 22743295
AN - SCOPUS:84865690782
SN - 1556-0864
VL - 7
SP - 1406
EP - 1416
JO - Journal of Thoracic Oncology
JF - Journal of Thoracic Oncology
IS - 9
ER -