title: Randomized phase II Study of carboplatin and etoposide with or without the bcl-2 antisense oligonucleotide oblimersen for extensive-stage small-cell lung cancer: CALGB 30103.
abstract: OBJECTIVE
  To assess the efficacy and toxicity of carboplatin, etoposide, and the bcl-2 antisense oligonucleotide oblimersen as initial therapy for extensive-stage small-cell lung cancer (ES-SCLC). bcl-2 has been implicated as a key factor in SCLC oncogenesis and chemotherapeutic resistance.
  
  
  METHODS
  A 3:1 randomized phase II study was performed to evaluate carboplatin and etoposide with (arm A) or without oblimersen (arm B) in 56 assessable patients with chemotherapy-naïve ES-SCLC. Outcome measures including toxicity, objective response rate, complete response rate, failure-free survival, overall survival, and 1-year survival rate.
  
  
  RESULTS
  Oblimersen was associated with slightly more grade 3 to 4 hematologic toxicity (88% v 60%; P = .05). Response rates were 61% (95% CI, 45% to 76%) for arm A and 60% (95% CI, 32% to 84%) for arm B. The percentage of patients alive at 1 year was 24% (95% CI, 12% to 40%) with oblimersen, and 47% (95% CI, 21% to 73%) without oblimersen. Hazard ratios for failure-free survival (1.79; P = .07) and overall survival (2.13; P = .02) suggested worse outcome for patients receiving oblimersen. These results hold when adjusted for other prognostic factors, such as weight loss, in multivariate regression analysis.
  
  
  CONCLUSIONS
  Despite extensive data supporting a critical role for Bcl-2 in chemoresistance in SCLC, addition of oblimersen to a standard regimen for this disease did not improve any clinical outcome measure. Emerging data from several groups suggest that this lack of efficacy may be due to insufficient suppression of Bcl-2 in vivo. Additional evaluation of this agent in SCLC is not warranted.
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center, David H. Koch Cancer Research Building, Suite 544, 1550 Orleans St, Baltimore, MD 21231, USA. rudin@jhmi.edu
authors.forename: Charles M
authors.initials: CM
authors.lastname: Rudin
authors.forename: Ravi
authors.initials: R
authors.lastname: Salgia
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Wang
authors.forename: Lydia D
authors.initials: LD
authors.lastname: Hodgson
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Masters
authors.forename: Mark
authors.initials: M
authors.lastname: Green
authors.forename: Everett E
authors.initials: EE
authors.lastname: Vokes
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D016017:Odds Ratio; D013873:Thionucleotides / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D013873:Thionucleotides; D005047:Etoposide; C408162:oblimersen; D016190:Carboplatin