title: Selumetinib in women with recurrent low-grade serous carcinoma of the ovary or peritoneum: an open-label, single-arm, phase 2 study.
abstract: BACKGROUND
  Low-grade serous carcinoma of the ovary is chemoresistant but mutations in the MAPK pathway could be targeted to control tumour growth. We therefore assessed the safety and activity of selumetinib, an inhibitor of MEK1/2, for patients with this cancer.
  
  
  METHODS
  In this open-label, single-arm phase 2 study, women (aged ≥18 years) with recurrent low-grade serous ovarian or peritoneal carcinoma were given selumetinib (50 mg twice daily, orally) until progression. The primary endpoint was the proportion of patients who had an objective tumour response according to RECIST version 1.1, assessed for all the treated patients. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00551070.
  
  
  RESULTS
  52 patients were enrolled between Dec 17, 2007, and Nov 23, 2009. All were eligible for analyses. Eight (15%) patients had an objective response to treatment-one patient had a complete response and seven had partial responses. 34 (65%) patients had stable disease. There were no treatment-related deaths. Grade 4 toxicities were cardiac (one), pain (one), and pulmonary events (one). Grade 3 toxicities that occurred in more than one patient were gastrointestinal (13), dermatological (nine), metabolic (seven), fatigue (six), anaemia (four), pain (four), constitutional (three), and cardiac events (two).
  
  
  CONCLUSIONS
  Selumetinib is well tolerated, and is active in the treatment of recurrent low-grade serous carcinoma of the ovary or peritoneum. The findings suggest that inhibitors of the MAPK pathway warrant further investigation in these patients.
  
  
  BACKGROUND
  National Cancer Institute.
authors.affiliation: Creighton University School of Medicine at St Joseph's Hospital and Medical Center, Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Phoenix, AZ, USA. John.farley@chw.edu
authors.forename: John
authors.initials: J
authors.lastname: Farley
authors.forename: William E
authors.initials: WE
authors.lastname: Brady
authors.forename: Vinod
authors.initials: V
authors.lastname: Vathipadiekal
authors.forename: Heather A
authors.initials: HA
authors.lastname: Lankes
authors.forename: Robert
authors.initials: R
authors.lastname: Coleman
authors.forename: Mark A
authors.initials: MA
authors.lastname: Morgan
authors.forename: Robert
authors.initials: R
authors.lastname: Mannel
authors.forename: S Diane
authors.initials: SD
authors.lastname: Yamada
authors.forename: David
authors.initials: D
authors.lastname: Mutch
authors.forename: William H
authors.initials: WH
authors.lastname: Rodgers
authors.forename: Michael
authors.initials: M
authors.lastname: Birrer
authors.forename: David M
authors.initials: DM
authors.lastname: Gershenson
mesh_terms: D000328:Adult; D000368:Aged; D001562:Benzimidazoles / Q000627:therapeutic use*; D018284:Cystadenocarcinoma, Serous / Q000188:drug therapy* / Q000235:genetics; D005260:Female; D006801:Humans; D020935:MAP Kinase Signaling System; D008875:Middle Aged; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors*; D009154:Mutation; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins / Q000235:genetics
chemical_list: C517975:AZD 6244; D001562:Benzimidazoles; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D020929:Mitogen-Activated Protein Kinase Kinases; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins