Phase 1 and pharmacokinetic study of everolimus in combination with cetuximab and carboplatin for recurrent/metastatic squamous cell carcinoma of the head and neck

摘要: BACKGROUND Platinum-based therapy combined with cetuximab is standard first-line for recurrent or metastatic squamous cell carcinoma of the head and neck (RMSCCHN). Preclinical studies have suggested that mammalian target rapamycin inhibitors may overcome resistance to epidermal growth factor receptor blockers augment antitumor activity. We conducted a phase 1b trial carboplatin, cetuximab, everolimus untreated RMSCCHN. METHODS Patients received carboplatin (area under curve = 2 mg/ml/min; 3 weeks on, 1 week off), (with loading dose 400 mg/m2 then 250 weekly), dose-escalating (2.5, 5.0, 7.5, 10 mg/day) 3+3 design. After 4 cycles, patients without progression continued cetuximab/everolimus until intolerable toxicity. Patients (age ≥ 18 years) had previously untreated, unresectable RMSCCHN not amenable radiotherapy an Eastern Cooperative Oncology Group performance status 0 2. RESULTS The study enrolled 20 (male/female = 18/2) RMSCCHN; median age was 65 years (44-75 years). Thirteen (male/female = 92%). Two 6 receiving 2.5 mg/day experienced dose-limiting toxicity (DLT) grade hyponatremia nausea. In 7 de-escalated (2.5 mg every other day), hyperglycemia produced DLT in patients. The objective response rate (RR) 61.5% (all partial responses). Progression-free survival (PFS) 8.15 months. pharmacokinetics described 2-compartment mixed-effects model. There significant correlation between tumor p-p44/42 staining (P = .044) marginally phosphorylated overall survival. CONCLUSIONS The maximum tolerated day. regimen associated encouraging RR PFS, this possible clinical efficacy select group neck. Cancer 2014;120:3940–3951. © 2014 American Society.