title: UCN-01 in combination with topotecan in patients with advanced recurrent ovarian cancer: a study of the Princess Margaret Hospital Phase II consortium.
abstract: OBJECTIVE
  UCN-01 is a staurosporine analogue shown to abrogate the G2 checkpoint through inhibition of cyclin-dependent kinases. Preclinical evidence suggests synergy between UCN-01 and cytotoxic chemotherapy. Topotecan is an active agent in ovarian cancer. This phase II study was conducted to investigate the safety and efficacy of topotecan and UCN-01 in patients with advanced ovarian cancer.
  
  
  METHODS
  A two-stage phase II trial was designed for patients with advanced ovarian cancer with progressive disease despite prior treatment with platinum and paclitaxel. Patients with advanced ovarian cancer were treated with topotecan, 1 mg/m(2) IV, days 1 to 5, and UCN-01 70 mg/m(2) on day 1 of the first cycle, and 35 mg/m(2) on day 1 of all subsequent cycles. Treatment was repeated on a 3-week cycle. The primary objective of this study was objective response rate while secondary objectives included rates of stable disease, duration of response, progression-free and overall survival, as well as toxicity. Tumor biopsy specimens were also collected where possible for molecular correlative studies.
  
  
  RESULTS
  Twenty-nine patients are evaluable for toxicity and efficacy. Three patients (10%) achieved a partial response. The median time to progression was 3.3 months (95% CI 1.5-NA), and the median overall survival was 9.7 months (95% CI: 7.5-15.3). The most common grade 3-4 toxicities were neutropenia (79%), anemia (41%), thrombocytopenia (14%), hyperglycemia (10%), and pain (10%).
  
  
  CONCLUSIONS
  The combination of UCN-01 and topotecan is generally well tolerated, however, this combination is not considered to have significant antitumor activity against advanced ovarian cancer.
authors.affiliation: Princess Margaret Hospital, Toronto, Ontario, Canada M56 2M9.
authors.forename: Stephen
authors.initials: S
authors.lastname: Welch
authors.forename: Hal W
authors.initials: HW
authors.lastname: Hirte
authors.forename: Mark S
authors.initials: MS
authors.lastname: Carey
authors.forename: Sebastian J
authors.initials: SJ
authors.lastname: Hotte
authors.forename: Ming-Sound
authors.initials: MS
authors.lastname: Tsao
authors.forename: Shirley
authors.initials: S
authors.lastname: Brown
authors.forename: Gregory R
authors.initials: GR
authors.lastname: Pond
authors.forename: Janet E
authors.initials: JE
authors.lastname: Dancey
authors.forename: Amit M
authors.initials: AM
authors.lastname: Oza
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D019311:Staurosporine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D019772:Topotecan / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: C054852:7-hydroxystaurosporine; D019772:Topotecan; D019311:Staurosporine