title: Phase II study of maintenance sunitinib following irinotecan and carboplatin as first-line treatment for patients with extensive-stage small-cell lung cancer.
abstract: BACKGROUND
  Inhibition of angiogenesis may be effective in the treatment of small-cell lung cancer (SCLC). Sunitinib, an oral agent that inhibits the VEGF signaling pathway, may delay progression in sequence with chemotherapy. This phase II trial was designed to evaluate the role of sunitinib monotherapy following 6 cycles of irinotecan and carboplatin in patients with newly diagnosed extensive-stage (ES) SCLC.
  
  
  METHODS
  Patients aged ≥18 years with previously untreated ES-SCLC were eligible. Additional criteria included: ECOG PS 0-1, no active brain metastases, and adequate organ function. Patients received 28-day cycles of irinotecan (60 mg/m(2), days 1, 8, 15) and carboplatin (AUC=4, day 1), and were assessed for response every 8 weeks. After 6 cycles of chemotherapy, patients with stable disease or responding disease proceeded to sunitinib monotherapy (25 mg orally daily) until disease progression or unacceptable toxicity. The primary endpoint was 1-year overall survival (OS).
  
  
  RESULTS
  Between 2/09 and 10/09, 34 patients (median age 65 years [range, 41-80]) were enrolled. 53% of patients were male, 47% had ECOG PS 0.21 patients (62%) completed 6 cycles of chemotherapy, and 17 (50%) initiated sunitinib monotherapy (median duration: 9 weeks; range, 2-28+weeks). After a median follow-up of 50 weeks (range: 37-68 weeks), 22 (62%) of the patients remain alive. The objective response rate with chemotherapy was 59%, and an additional 20% had stable disease. 1-year OS was 54% and median time to progression was 7.6 months. Grade 3/4 toxicity was rare during sunitinib monotherapy.
  
  
  CONCLUSIONS
  This phase II trial provides support for further study of sunitinib maintenance therapy following platinum-doublet chemotherapy in patients with ES-SCLC. The 1 year OS of 54% is encouraging, and a randomized trial would be appropriate to assess sunitinib's impact following chemotherapy.
authors.affiliation: Sarah Cannon Research Institute, Nashville, TN 37203, USA. dspigel@tnonc.com
authors.forename: David R
authors.initials: DR
authors.lastname: Spigel
authors.forename: F Anthony
authors.initials: FA
authors.lastname: Greco
authors.forename: Mark S
authors.initials: MS
authors.lastname: Rubin
authors.forename: Dianna
authors.initials: D
authors.lastname: Shipley
authors.forename: Dana S
authors.initials: DS
authors.lastname: Thompson
authors.forename: Eric T
authors.initials: ET
authors.lastname: Lubiner
authors.forename: Janice F
authors.initials: JF
authors.lastname: Eakle
authors.forename: Raven
authors.initials: R
authors.lastname: Quinn
authors.forename: Howard A
authors.initials: HA
authors.lastname: Burris
authors.forename: John D
authors.initials: JD
authors.lastname: Hainsworth
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D016190:Carboplatin / Q000008:administration & dosage; D018450:Disease Progression; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D060828:Induction Chemotherapy; D000077146:Irinotecan; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D060046:Maintenance Chemotherapy / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011758:Pyrroles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D000077210:Sunitinib; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; D000077146:Irinotecan; D016190:Carboplatin; D000077210:Sunitinib; D002166:Camptothecin