title: 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: Department of Hematology and Medical Oncology, Emory University, Winship Cancer Institute, 1365 Clifton Road NE, Atlanta, GA 30322, USA. ssramal@emory.edu
authors: Suresh S
authors: SS
authors: Ramalingam
authors: Taofeek K
authors: TK
authors: Owonikoko
authors: Madhusmita
authors: M
authors: Behera
authors: Janakiraman
authors: J
authors: Subramanian
authors: Nabil F
authors: NF
authors: Saba
authors: Scott A
authors: SA
authors: Kono
authors: Anthony A
authors: AA
authors: Gal
authors: Gabriel
authors: G
authors: Sica
authors: R Donald
authors: RD
authors: Harvey
authors: Zhengjia
authors: Z
authors: Chen
authors: Carmen M
authors: CM
authors: Klass
authors: Dong M
authors: DM
authors: Shin
authors: Haian
authors: H
authors: Fu
authors: Shi-yong R
authors: SY
authors: Sun
authors: Ramaswamy
authors: R
authors: Govindan
authors: Fadlo R
authors: FR
authors: Khuri
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000077143:Docetaxel; D000068338:Everolimus; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D020123:Sirolimus / Q000008:administration & dosage / Q000031:analogs & derivatives; D015996:Survival Rate; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D043823:Taxoids / Q000008:administration & dosage
chemical_list: D014408:Biomarkers, Tumor; D043823:Taxoids; D000077143:Docetaxel; D000068338:Everolimus; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus