title: A phase II trial of the Src-kinase inhibitor saracatinib after four cycles of chemotherapy for patients with extensive stage small cell lung cancer: NCCTG trial N-0621.
abstract: BACKGROUND
  To assess the efficacy and the Src-kinase inhibitor saracatinib (AZD-0530) after four cycles of platinum-based chemotherapy for extensive stage small cell lung cancer (SCLC).
  
  
  METHODS
  Patients with at least stable disease received saracatinib at a dose of 175 mg/day by mouth until disease progression, unacceptable toxicity, or patient refusal. The primary endpoint was the 12-week progression-free survival (PFS) rate from initiation of saracatinib treatment. Planned interim analysis in first 20 patients, where 13 or more patients alive and progression-free at 12-weeks would allow continued enrollment to 40 total patients.
  
  
  RESULTS
  All 23 evaluable patients received platinum based standard chemotherapy. Median age was 58 years (range: 48-82). 96% of patients had a performance status of 0/1. Median of two cycles given (range: 1-34). All 23 (100%) patients have ended treatment, most for disease progression (19/23). The 12-week PFS rate was 26% (6/23; 95% CI: 10-48%). From start of standard chemotherapy, median PFS was 4.7 months (95% CI: 4.5-5.1) and median OS was 11.2 months (95% CI: 9.9-13.8). Eight (35%) and three (13%) patients experienced at least one grade 3/4 or grade 4 AE, respectively. Commonly occurring grade 3/4 adverse events were thrombocytopenia (13%), fatigue (9%), nausea (9%), and vomiting (9%).
  
  
  CONCLUSIONS
  Saracatinib at a dose of 175 mg/day by mouth is well tolerated. However, the PFS rate observed at the pre-planned interim analysis did not meet the criteria for additional enrollment.
authors: Division of Medical Oncology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, United States. Electronic address: molina.julian@mayo.edu.
authors: Julian R
authors: JR
authors: Molina
authors: Division of Biomedical Statistics and Informatics, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, United States.
authors: Nathan R
authors: NR
authors: Foster
authors: Division of Medical Oncology, Department of Internal Medicine, Ramathibodi Hospital, Bangkok, Thailand.
authors: Thanyanan
authors: T
authors: Reungwetwattana
authors: Division of Biomedical Statistics and Informatics, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, United States.
authors: Garth D
authors: GD
authors: Nelson
authors: Columbus Oncology & Hematology, Inc., 810 Jasonway Avenue, Suite A, Columbus, OH 43214l, United States.
authors: Andrew V
authors: AV
authors: Grainger
authors: MeritCare Hospital CCOP, 820 4(th) Street North, Fargo, ND 58102, United States.
authors: Preston D
authors: PD
authors: Steen
authors: St. Joseph Mercy Cancer Center, 5301 McAuley Drive, Suite C-139, Ypsilanti, MI 48197, United States.
authors: Philip J
authors: PJ
authors: Stella
authors: Division of Medical Oncology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, United States.
authors: Randolph
authors: R
authors: Marks
authors: CTEP Program, National Cancer Institute, Executive Plaza North, Suite 7115A, Rockville, MD 20852-7426, United States.
authors: John
authors: J
authors: Wright
authors: Roswell Park Cancer Institute, Elm and Carlton Street, Buffalo, NY 14263, United States.
authors: Alex A
authors: AA
authors: Adjei
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D052117:Benzodioxoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D019233:Retreatment; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D016896:Treatment Outcome; D019061:src-Family Kinases / Q000037:antagonists & inhibitors
chemical_list: D000970:Antineoplastic Agents; D052117:Benzodioxoles; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; C515233:saracatinib; D019061:src-Family Kinases
keywords: C-Src; Extensive stage; Maintenance; Saracatinib; Small cell lung cancer