title: A phase II study of obatoclax mesylate, a Bcl-2 antagonist, plus topotecan in relapsed small cell lung cancer.
abstract: BACKGROUND
  We previously reported data on the safety, tolerability, and recommended phase II dose of obatoclax mesylate in conjunction with topotecan in patients with advanced solid tumor malignancies. Preliminary efficacy data suggested activity in patients with recurrent small cell lung cancer (SCLC). Based on these data, we performed a phase II study of obatoclax mesylate plus topotecan in patients with relapsed SCLC to assess efficacy.
  
  
  METHODS
  This was an open-label, single-arm, phase II extension of obatoclax mesylate plus topotecan in patients with relapsed SCLC. Obatoclax mesylate was given intravenously (IV) at a dose of 14mg/m(2) on days 1 and 3 with IV topotecan at 1.25mg/m(2) on days 1-5 of an every 3-week cycle. The primary end-point of this study was overall response rate.
  
  
  RESULTS
  Nine patients with recurrent SCLC were enrolled into the first stage of the study. Patients received a median of 2 cycles of treatment. All patients were evaluable for the primary end-point of overall response. There were no partial or complete responses. Five patients (56%) had stable disease. The remaining four patients (44%) developed progressive disease. The most common grade 3 or 4 adverse events included thrombocytopenia (22%), anemia (11%), neutropenia (11%), and ataxia (11%).
  
  
  CONCLUSIONS
  Obatoclax mesylate added to topotecan does not exceed the historic response rate seen with topotecan alone in patients with relapsed SCLC following the first-line platinum-based therapy.
authors.affiliation: Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: Paul K
authors.initials: PK
authors.lastname: Paik
authors.forename: Charles M
authors.initials: CM
authors.lastname: Rudin
authors.forename: Maria C
authors.initials: MC
authors.lastname: Pietanza
authors.forename: Andrew
authors.initials: A
authors.lastname: Brown
authors.forename: Naiyer A
authors.initials: NA
authors.lastname: Rizvi
authors.forename: Naoko
authors.initials: N
authors.lastname: Takebe
authors.forename: William
authors.initials: W
authors.lastname: Travis
authors.forename: Leonard
authors.initials: L
authors.lastname: James
authors.forename: Michelle S
authors.initials: MS
authors.lastname: Ginsberg
authors.forename: Rosalyn
authors.initials: R
authors.lastname: Juergens
authors.forename: Susan
authors.initials: S
authors.lastname: Markus
authors.forename: Leslie
authors.initials: L
authors.lastname: Tyson
authors.forename: Sara
authors.initials: S
authors.lastname: Subzwari
authors.forename: Mark G
authors.initials: MG
authors.lastname: Kris
authors.forename: Lee M
authors.initials: LM
authors.lastname: Krug
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000503:physiopathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D007211:Indoles; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000503:physiopathology; D008875:Middle Aged; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors; D011758:Pyrroles / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D012008:Recurrence; D013921:Thrombocytopenia / Q000209:etiology; D019772:Topotecan / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D007211:Indoles; D019253:Proto-Oncogene Proteins c-bcl-2; D011758:Pyrroles; D019772:Topotecan; C520962:obatoclax