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Author Notes:

Correspondence: Suresh S. Ramalingam, MD, Associate Professor, Emory University, Winship Cancer Institute, 1365 Clifton Road, C-3090, Atlanta, GA 30322. Email: ssramal@emory.edu. Phone: 404-778-5378. Fax: 404-778-5520

Disclosures: Suresh S. Ramalingam, Taofeek K. Owonikoko, Shi-Yong Sun, Dong M. Shin and Fadlo R. Khuri are Distinguished Cancer Scholars of the Georgia Cancer Coalition.

Merrill J. Egorin is an ASCO Cancer Foundation Translational Research Professor.


Research Funding:

Supported by NCI 5 P01 CA116676-03and, in part, by Novartis pharmaceuticals.


  • Everolimus
  • docetaxel
  • phase I
  • pharmacokinetics
  • non-small cell lung cancer

Phase I and pharmacokinetic study of everolimus, an mTOR inhibitor, in combination with docetaxel for recurrent/refractory non-small cell lung cancer

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Journal Title:



Volume 116, Number 16


, Pages 3903-3909

Type of Work:

Article | Post-print: After Peer Review


Purpose Everolimus is a novel inhibitor of the mammalian target of rapamycin (mTOR) pathway, which is aberrantly activated in non-small cell lung cancer (NSCLC). We conducted a phase I and pharmacokinetic study of everolimus and docetaxel for recurrent NSCLC. Methods Patients with advanced stage NSCLC and progression following prior platinum-based chemotherapy were eligible. Sequential cohorts were treated with escalating doses of docetaxel (day 1) and everolimus (PO daily, days 1–19), every 3 weeks. Pharmacokinetic (PK) sampling of everolimus and docetaxel were done in cycle 1. The primary endpoint was determination of the recommended phase II doses (RP2D) of the combination. Results Twenty-four patients were enrolled. Median age, 62 yrs; Females, 11; number of prior regimens, 1(n=13), 2 (n=6), ≥3 (n=5) ECOG PS 0(n=6), 1(n=17). The dose-limiting toxicities (DLT) were fever with grade 3/4 neutropenia, grade 3 fatigue and grade 3 mucositis. None of the 7 patients treated at the RP2D (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 ±SD AUC-based accumulation factors (R) for everolimus on days 8 and 15 were 1.16 ± 0.37 and 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 RP2D of docetaxel and everolimus for combination therapy are 60 mg/m2 and 5 mg PO daily, respectively. Promising anti-cancer activity has been noted.

Copyright information:

© 2010 American Cancer Society

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