Randomized phase II study of carboplatin and etoposide with or without obatoclax mesylate in extensive-stage small cell lung cancer.

Autor: Langer CJ; Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, United States. Electronic address: corey.langer@uphs.upenn.edu., Albert I; Mátrai Gyógyintézet, Mátraháza, Hungary., Ross HJ; Mayo Clinic, Scottsdale, AZ, United States., Kovacs P; University of Debrecen, Debrecen, Hungary., Blakely LJ; The West Clinic, Memphis, TN, United States., Pajkos G; Bacs-Kiskun County Hospital, Kecskemét, Hungary., Somfay A; University of Szeged, Szeged, Hungary., Zatloukal P; Charles University, Faculty Hospital Bulovka and Postgraduate Medical Institute, Prague, Czech Republic., Kazarnowicz A; Tuberculosis and Lung Disease Hospital, Olsztyn, Poland., Moezi MM; Cancer Specialists of North Florida, Jacksonville, FL, United States., Schreeder MT; Clearview Cancer Institute, Huntsville, AL, United States., Schnyder J; Gemin X Pharmaceuticals, Malvern, PA, United States., Ao-Baslock A; Powered 4 Significance LLC, Bloomsbury, NJ, United States., Pathak AK; Teva Pharmaceuticals, Frazer, PA, United States., Berger MS; Gemin X Pharmaceuticals, Malvern, PA, United States.
Jazyk: angličtina
Zdroj: Lung cancer (Amsterdam, Netherlands) [Lung Cancer] 2014 Sep; Vol. 85 (3), pp. 420-8. Date of Electronic Publication: 2014 May 13.
DOI: 10.1016/j.lungcan.2014.05.003
Abstrakt: Objective: This randomized phase II study assessed the efficacy and safety of obatoclax mesylate, a small-molecule Bcl-2 inhibitor, added to carboplatin/etoposide chemotherapy as initial treatment for extensive-stage small-cell lung cancer (ES-SCLC).
Materials and Methods: Chemotherapy-naïve subjects with ES-SCLC and Eastern Cooperative Oncology Group performance status (ECOG PS) 0-2 received carboplatin/etoposide with (CbEOb) or without (CbE) obatoclax for up to six cycles. Responders to CbEOb could receive maintenance obatoclax until disease progression. The primary endpoint was objective response rate (ORR).
Results: 155 subjects (median age 62, 58% male, 10% ECOG PS 2) were treated with CbEOb (n=77) or CbE (n=78); 65% and 59% of subjects, respectively, completed six cycles. ORR was 62% with CbEOb versus 53% with CbE (1-sided p=0.143). Clinical benefit (ORR+ stable disease) trended better with CbEOb (81% versus 68%; p=0.054). Median progression-free survival (PFS) and overall survival (OS) were 5.8 months (95% confidence interval [CI]: 5.3-6.5) and 10.5 months (8.9-13.8) with CbEOb and 5.2 months (95% CI: 4.1-5.7) and 9.8 months (7.2-11.2) with CbE. Median OS was 10.5 months (95% CI: 8.9-13.8) and 9.8 months (7.2-11.2) with a nonsignificant hazard ratio for OS, 0.823; 1-sided p=0.121. Grade 3/4 adverse events (AEs) were primarily hematologic and similar in frequency between treatment arms. Obatoclax-related somnolence and euphoria were grade 1/2, transient, and did not require treatment discontinuation.
Conclusion: Obatoclax was well tolerated when added to carboplatin/etoposide in first-line treatment of ES-SCLC, but failed to significantly improve ORR, PFS, or OS.
(Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)
Databáze: MEDLINE
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