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BACKGROUND: Everolimus is a novel inhibitor of the mammalian target of rapamycin pathway, which is aberrantlyactivated in nonsmall cell lung cancer (NSCLC). The authors conducted a phase 1 and pharmacokinetic study of everolimus and docetaxel for recurrent NSCLC. METHODS: Patients with advanced stage NSCLC and progression after prior platinum-based chemotherapy were eligible. Sequential cohorts were treated with escalating doses of docetaxel(Day 1) and everolimus (orally daily, Days 1-19) every 3 weeks. Pharmacokinetic sampling of everolimus and docetaxelwas done in Cycle 1. The primary endpoint was determination of the recommended phase 2 doses of the combination. RESULTS: Twenty-four patients were enrolled (median age, 62 years; women, 11; number of prior regimens, 1 [n = 13], 2 [n = 6], ≥3[ n = 5]; Eastern Cooperative Oncology Group performance status, 0 [n = 6], 1 [n = 17]). Thedose-limiting toxicities (DLTs) were fever with grade 3/4 neutropenia, grade 3 fatigue, and grade 3 mucositis. Noneof the 7 patients treated at the recommended phase 2 dose (docetaxel 60 mg/m² and everolimus 5 mg daily) experienced DLT. Everolimus area under the concentration time curve (AUC) was not different with 60 or 75 mg/m² docetaxel. Mean ± standard deviation AUC-based accumulation factors for everolimus on Days 8 and 15 were 1.16 ± 0.37and 1.42 ±0.42, respectively. Docetaxel Day 1 half-life was 9.4 ± 3.4 hours. Among 21 patients evaluable, 1 had a partial response, and 10 had disease stabilization. CONCLUSIONS: The recommended phase 2 doses of docetaxel and everolimus for combination therapy are 60 mg/m² and 5 mg orally daily, respectively. Promising anticancer activityhas been noted. [ABSTRACT FROM AUTHOR]