TY - JOUR
T1 - Brief report
T2 - A phase II "window-of-opportunity" frontline study of the mTOR inhibitor, temsirolimus given as a single agent in patients with advanced NSCLC, an NCCTG study
AU - Reungwetwattana, Thanyanan
AU - Molina, Julian R.
AU - Mandrekar, Sumithra J.
AU - Allen-Ziegler, Katie
AU - Rowland, Kendrith M.
AU - Reuter, Nicholas F.
AU - Luyun, Ronnie F.
AU - Dy, Grace K.
AU - Marks, Randolph S.
AU - Schild, Steven E.
AU - Jett, James R.
AU - Adjei, Alex A.
N1 - Funding Information:
Funding by NCI; NCCTG grant number: CA-25224.
PY - 2012
Y1 - 2012
N2 - Background: In an effort to evaluate the single agent activity of temsirolimus in previously untreated non-small-cell lung cancer, the North Central Cancer Treatment Group undertook a frontline "window- of-opportunity" study. Methods: Patients received 25 mg of temsirolimus administered intravenously as a weekly 30 minute infusion, on a 4-week cycle. Based on a two-stage Fleming design, the treatment would be promising if at least four of the first 25 evaluable patients in stage I or at least six of the 50 evaluable patients at the end of stage II have a confirmed response. Fresh tumor biopsies were obtained to evaluate predictive markers of temsirolimus activity. Results: A total of 55 patients were enrolled with 52 patients being evaluable. The median age was 64 years. Adverse events (grade 3/4) occurring in 33 patients included dyspnea (12%), fatigue (10%), hyperglycemia (8%), hypoxia (8%), nausea (8%), and rash/desquamation (6%). The clinical benefit rate was 35% with four patients achieving a confirmed partial response and 14 patients with stable disease for 8 weeks or more. The 24-week progression-free survival rate was 25%. Median progression-free survival and overall survival were 2.3 and 6.6 months, respectively. Expression of p70s6 kinase, phospho-p70s6 kinase, Akt, phospho-Akt, and phosphatase and tensin homolog mutation did not correlate with clinical outcome. Conclusions: Temsirolimus given as a single agent in frontline therapy in patients with non-small-cell lung cancer was tolerable and demonstrated clinical benefit but did not meet the primary objective in this study. Patient selection will be needed to enhance the efficacy.
AB - Background: In an effort to evaluate the single agent activity of temsirolimus in previously untreated non-small-cell lung cancer, the North Central Cancer Treatment Group undertook a frontline "window- of-opportunity" study. Methods: Patients received 25 mg of temsirolimus administered intravenously as a weekly 30 minute infusion, on a 4-week cycle. Based on a two-stage Fleming design, the treatment would be promising if at least four of the first 25 evaluable patients in stage I or at least six of the 50 evaluable patients at the end of stage II have a confirmed response. Fresh tumor biopsies were obtained to evaluate predictive markers of temsirolimus activity. Results: A total of 55 patients were enrolled with 52 patients being evaluable. The median age was 64 years. Adverse events (grade 3/4) occurring in 33 patients included dyspnea (12%), fatigue (10%), hyperglycemia (8%), hypoxia (8%), nausea (8%), and rash/desquamation (6%). The clinical benefit rate was 35% with four patients achieving a confirmed partial response and 14 patients with stable disease for 8 weeks or more. The 24-week progression-free survival rate was 25%. Median progression-free survival and overall survival were 2.3 and 6.6 months, respectively. Expression of p70s6 kinase, phospho-p70s6 kinase, Akt, phospho-Akt, and phosphatase and tensin homolog mutation did not correlate with clinical outcome. Conclusions: Temsirolimus given as a single agent in frontline therapy in patients with non-small-cell lung cancer was tolerable and demonstrated clinical benefit but did not meet the primary objective in this study. Patient selection will be needed to enhance the efficacy.
KW - Advanced non-small-cell lung carcinoma
KW - MTOR inhibitors
KW - Temsirolimus
KW - Window of opportunity
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U2 - 10.1097/JTO.0b013e31824de0d6
DO - 10.1097/JTO.0b013e31824de0d6
M3 - Article
C2 - 22722792
AN - SCOPUS:84862133526
SN - 1556-0864
VL - 7
SP - 919
EP - 922
JO - Journal of Thoracic Oncology
JF - Journal of Thoracic Oncology
IS - 5
ER -