title: Irinotecan, carboplatin, and imatinib in untreated extensive-stage small-cell lung cancer: a phase II trial of the Minnie Pearl Cancer Research Network.
abstract: BACKGROUND
  The tyrosine kinase KIT has variable expression in small-cell lung cancer (SCLC) and may be a prognostic factor. Imatinib targets KIT expression, providing rationale for studying its role in combination with chemotherapy in SCLC in a multicenter phase II trial.
  
  
  METHODS
  Patients with untreated extensive-stage SCLC received carboplatin area under the concentration-time curve of 4 on day 1; irinotecan 60 mg/m2 on days 1, 8, and 15; and imatinib 600 mg/day. Treatment cycles were 28 days. Patients remained on imatinib until progressive disease or significant toxicity.
  
  
  RESULTS
  Between September 2002 and May 2004, 68 patients were enrolled in this multicenter trial. Median age was 60 years (range, 37-81). The objective response rate was 66% (95% confidence interval: 54%-76%). Median progression-free survival was 5.4 months (95% CI: 4.3-6.0 months). Median overall survival was 8.4 months (95% CI: 6.3-10.5 months). Thirty-five percent of patients were alive at 1 year. Grade 3/4 hematologic toxicity included neutropenia (43%), anemia (16%), and thrombocytopenia (9%). Grade 3 nonhematologic toxicity included diarrhea (19%), fatigue (24%), and nausea (26%). Forty-eight of 56 patients (86%) with available tumor specimens had KIT expression detected. KIT expression did not appear to correlate with progression-free survival or overall survival in a retrospective analysis.
  
  
  CONCLUSIONS
  Irinotecan, carboplatin, and imatinib is a safe and generally well-tolerated regimen in patients with SCLC. However, the addition of imatinib did not improve results from those expected with chemotherapy alone.
authors.affiliation: Sarah Cannon Research Institute and Tennessee Oncology, PLLC, Nashville, Tennessee 37203, USA.
authors.forename: David R
authors.initials: DR
authors.lastname: Spigel
authors.forename: John D
authors.initials: JD
authors.lastname: Hainsworth
authors.forename: Lisa
authors.initials: L
authors.lastname: Simons
authors.forename: Christina
authors.initials: C
authors.lastname: Meng
authors.forename: Howard A
authors.initials: HA
authors.lastname: Burris
authors.forename: Denise A
authors.initials: DA
authors.lastname: Yardley
authors.forename: Richard
authors.initials: R
authors.lastname: Grapski
authors.forename: Marshall
authors.initials: M
authors.lastname: Schreeder
authors.forename: Padmaja V
authors.initials: PV
authors.lastname: Mallidi
authors.forename: F Anthony
authors.initials: FA
authors.lastname: Greco
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001549:Benzamides; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016190:Carboplatin / Q000008:administration & dosage*; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D018450:Disease Progression; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000068877:Imatinib Mesylate; D007262:Infusions, Intravenous; D000077146:Irinotecan; D008175:Lung Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging / Q000379:methods; D010879:Piperazines / Q000008:administration & dosage*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011743:Pyrimidines / Q000008:administration & dosage*; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage*; D012189:Retrospective Studies; D015996:Survival Rate; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D014768:Virginia / Q000453:epidemiology