Phase II study of docetaxel in combination with everolimus for second- or third-line therapy of advanced non-small-cell lung cancer.

Abstract

We conducted a phase II study of docetaxel in combination with everolimus, a mammalian target of rapamycin (mTOR) inhibitor, for salvage therapy of advanced non-small-cell lung cancer (NSCLC) based on promising preclinical and early-phase clinical data. Patients with advanced-stage NSCLC treated with one or two previous systemic therapy regimens were given docetaxel (60 mg/m) and everolimus (5 mg orally once daily on days 1-19) every 3 weeks. Archived tumor specimens were evaluated for markers of mTOR pathway activation (total and phosphorylated mTOR, Akt, S6, eIF4e, and 4EBP1). Twenty-eight patients were enrolled (median age: 62 years; male: 13; Caucasians: 19; adenocarcinoma: 20; performance status 0, 3; performance status 1, 23; 1 previous regimen, 16). A median of 3.5 cycles of therapy was administered. Two patients experienced partial response and 15 had stable disease (clinical benefit rate, 70%). The 6-month progression-free survival rate was 5%, and the median overall survival was 9.6 months. Low pAkt expression correlated with clinical benefit rate (p = 0.01) but not with progression-free survival or overall survival. The combination of everolimus and docetaxel was tolerated well, but the efficacy was relatively modest in an unselected population of patients with NSCLC.

• Authors: Suresh S Ramalingam, Taofeek K Owonikoko, Madhusmita Behera, Janakiraman Subramanian, Nabil F Saba, Scott A Kono, Anthony A Gal, Gabriel Sica, R Donald Harvey, Zhengjia Chen, Carmen M Klass, Dong M Shin, Haian Fu, Shi-yong R Sun, Ramaswamy Govindan, Fadlo R Khuri
• Journal: Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer (J Thorac Oncol) Vol. 8 Issue 3 Pg. 369-72 (Mar 2013) ISSN: 1556-1380 [Electronic] United States
• PMID: 23407561 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• Taxoids
• Docetaxel
• Everolimus
• MTOR protein, human
• TOR Serine-Threonine Kinases
• Sirolimus

Topics

• Adenocarcinoma (drug therapy, mortality, pathology)
• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Biomarkers, Tumor (metabolism)
• Carcinoma, Non-Small-Cell Lung (drug therapy, mortality, pathology)
• Carcinoma, Squamous Cell (drug therapy, mortality, pathology)
• Docetaxel
• Everolimus
• Female
• Follow-Up Studies
• Humans
• Lung Neoplasms (drug therapy, mortality, pathology)
• Male
• Middle Aged
• Neoplasm Staging
• Prognosis
• Sirolimus (administration & dosage, analogs & derivatives)
• Survival Rate
• TOR Serine-Threonine Kinases (metabolism)
• Taxoids (administration & dosage)