title: Multicenter, randomized phase II trial of oral CI-1033 for previously treated advanced ovarian cancer.
abstract: OBJECTIVE
  To evaluate the antitumor activity and toxicity of two doses of CI-1033 in patients with platinum-refractory or recurrent ovarian cancer, and to determine baseline expression of epidermal growth factor receptor in tumor cells.
  
  
  METHODS
  This phase II, open-label clinical trial evaluated CI-1033 in patients with ovarian cancer who failed prior platinum-based therapy. Two oral doses of CI-1033 were evaluated--a 50-mg and a 200--mg oral dose administered daily for 21 days in a 28-day cycle. Patients were evaluated for tumor response and toxicity; in addition, archival baseline tumor samples were analyzed by immunohistochemistry for erbB1 to erbB4 status.
  
  
  RESULTS
  One hundred five eligible patients were treated. Baseline demographic characteristics were balanced in this heavily pretreated patient population. The median number of prior chemotherapy regimens received was four. The most commonly encountered drug-related adverse events for both dose arms were gastrointestinal (diarrhea, nausea, stomatitis) toxicity, asthenia, and rash. No responses were observed. Stable disease was confirmed in 34% and 26% of patients in the 200-mg and 50-mg arms, respectively, and 1-year survival rates were 38.5% and 37.7%, respectively. Baseline erbB3 and erbB4 revealed the highest frequencies of expression, while erbB2 was the lowest.
  
  
  CONCLUSIONS
  CI-1033 did not show activity in unscreened patients with advanced ovarian cancer. At 50 mg/d, CI-1033 had a more favorable adverse events profile than at 200 mg/d. erbB3 and erbB4 receptors showed the highest expression in tumor samples while erbB2 revealed the least. There appears to be no association between baseline erbB expression and disease stability.
authors.affiliation: Dana-Farber Cancer Institute, 44 Binney St, Boston, MA 02115, USA. Susana_Campos@dfci.harvard.edu
authors.forename: Susana
authors.initials: S
authors.lastname: Campos
authors.forename: Oday
authors.initials: O
authors.lastname: Hamid
authors.forename: Michael V
authors.initials: MV
authors.lastname: Seiden
authors.forename: Amit
authors.initials: A
authors.lastname: Oza
authors.forename: Marie
authors.initials: M
authors.lastname: Plante
authors.forename: Ronald K
authors.initials: RK
authors.lastname: Potkul
authors.forename: Peter F
authors.initials: PF
authors.lastname: Lenehan
authors.forename: Eric P
authors.initials: EP
authors.lastname: Kaldjian
authors.forename: Mary L
authors.initials: ML
authors.lastname: Varterasian
authors.forename: Cheryl
authors.initials: C
authors.lastname: Jordan
authors.forename: Claudie
authors.initials: C
authors.lastname: Charbonneau
authors.forename: Hal
authors.initials: H
authors.lastname: Hirte
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D018450:Disease Progression; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D006801:Humans; D008875:Middle Aged; D009025:Morpholines / Q000008:administration & dosage* / Q000009:adverse effects; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D018739:Oncogene Proteins v-erbB / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D009025:Morpholines; D018739:Oncogene Proteins v-erbB; C420268:Canertinib; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases