Phase 1 and pharmacokinetic study of everolimus in combination with cetuximab and carboplatin for recurrent/metastatic squamous cell carcinoma of the head and neck
Nabil F. Saba, Selwyn J. Hurwitz, Kelly Magliocca, Sungjin Kim, Taofeek K. Owonikoko, Donald Harvey, Suresh S. Ramalingam, Zhengjia Chen, Jackie Rogerio, Jennifer Mendel, Scott A. Kono, Colleen Lewis, Amy Y. Chen, Kristin Higgins, Mark El-Deiry, Trad Wadsworth, Jonathan J. Beitler, Dong M. Shin, Shi-Yong Sun and Fadlo R. Khuri
Article first published online: 7 AUG 2014 | DOI: 10.1002/cncr.28965
This article describes clinical, pharmacokinetic, and tissue biomarker correlative studies in a phase 1 trial of patients with recurrent or metastatic squamous cell carcinoma of the head and neck combining for the first time a platinum (carboplatin) with cetuximab and everolimus. The combination of 2 biomarkers, the p-p44/42 weighted index and the phosphorylated mammalian target of rapamycin weighted index, has a high predictive discrimination power for a clinical response (areas under the curve of 0.9583 and 0.9167, respectively). A 2-compartment mixed-effects pharmacokinetic model is consistent with previously described studies. The maximum tolerated dose of everolimus in this combination is 2.5 mg every other day. Despite the observed toxicities, this combination is associated with an encouraging response rate and progression-free survival and may deserve further investigation in a better selected population.