Elsevier

Journal of Thoracic Oncology

Volume 7, Issue 9, September 2012, Pages 1406-1416
Journal of Thoracic Oncology

Original Article
Sunitinib Plus Erlotinib for the Treatment of Advanced/Metastatic Non–Small-Cell Lung Cancer: A Lead-In Study

https://doi.org/10.1097/JTO.0b013e31825cca1cGet rights and content
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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.

Key Words

Non–small-cell lung cancer
Sunitinib
Erlotinib
Safety
Pharmacokinetics

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Disclosure: Tiziana Usari is an employee of Pfizer, the manufacturer of sunitinib. Ana Ruiz-Garcia, Lesley Tye, and Richard Chao are all employees of Pfizer and hold stock in the company. The other authors declare no conflicts of interest.