title: Randomized phase II study of carboplatin and etoposide with or without obatoclax mesylate in extensive-stage small cell lung cancer.
abstract: 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).
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, United States. Electronic address: corey.langer@uphs.upenn.edu.
authors.forename: Corey J
authors.initials: CJ
authors.lastname: Langer
authors.affiliation: Mátrai Gyógyintézet, Mátraháza, Hungary.
authors.forename: Istvan
authors.initials: I
authors.lastname: Albert
authors.affiliation: Mayo Clinic, Scottsdale, AZ, United States.
authors.forename: Helen J
authors.initials: HJ
authors.lastname: Ross
authors.affiliation: University of Debrecen, Debrecen, Hungary.
authors.forename: Peter
authors.initials: P
authors.lastname: Kovacs
authors.affiliation: The West Clinic, Memphis, TN, United States.
authors.forename: L Johnetta
authors.initials: LJ
authors.lastname: Blakely
authors.affiliation: Bacs-Kiskun County Hospital, Kecskemét, Hungary.
authors.forename: Gabor
authors.initials: G
authors.lastname: Pajkos
authors.affiliation: University of Szeged, Szeged, Hungary.
authors.forename: Attila
authors.initials: A
authors.lastname: Somfay
authors.affiliation: Charles University, Faculty Hospital Bulovka and Postgraduate Medical Institute, Prague, Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Zatloukal
authors.affiliation: Tuberculosis and Lung Disease Hospital, Olsztyn, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Kazarnowicz
authors.affiliation: Cancer Specialists of North Florida, Jacksonville, FL, United States.
authors.forename: Mehdi M
authors.initials: MM
authors.lastname: Moezi
authors.affiliation: Clearview Cancer Institute, Huntsville, AL, United States.
authors.forename: Marshall T
authors.initials: MT
authors.lastname: Schreeder
authors.affiliation: Gemin X Pharmaceuticals, Malvern, PA, United States.
authors.forename: Judy
authors.initials: J
authors.lastname: Schnyder
authors.affiliation: Powered 4 Significance LLC, Bloomsbury, NJ, United States.
authors.forename: Ada
authors.initials: A
authors.lastname: Ao-Baslock
authors.affiliation: Teva Pharmaceuticals, Frazer, PA, United States.
authors.forename: Ashutosh K
authors.initials: AK
authors.lastname: Pathak
authors.affiliation: Gemin X Pharmaceuticals, Malvern, PA, United States.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Berger
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D015897:Comorbidity; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007211:Indoles; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011758:Pyrroles / Q000008:administration & dosage; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D016896:Treatment Outcome
chemical_list: D007211:Indoles; D011758:Pyrroles; D005047:Etoposide; D016190:Carboplatin; C520962:obatoclax
keywords: Bcl-2; Carboplatin; Etoposide; Obatoclax; Randomized; SCLC