title: A phase I-II study of elacytarabine (CP-4055) in the treatment of patients with ovarian cancer resistant or refractory to platinum therapy.
abstract: OBJECTIVE
  Treatment of patients with recurrent ovarian cancer remains a challenge, and there is a need for new and more effective agents. A phase I-II study was designed to determine the recommended dose (RD) and the anti-tumour effect of a prolonged administration of elacytarabine, the elaidic ester of cytarabine, in patients with refractory/resistant recurrent ovarian cancer.
  
  
  METHODS
  The primary objective of the dose escalation phase I part was to determine the RD for elacytarabine when given twice for five consecutive days in a 4-week schedule, D1-5 and D8(+2)-12(+2) q4w. Three to six patients were to be enrolled at each dose level. The start dose was elacytarabine 75 mg/m(2)/day. The phase II part was designed as a two-step study based on response.
  
  
  RESULTS
  A total of 28 patients entered the study, 17 patients in the phase I part and 11(#) patients in phase II. Three dose levels were tested: 75 mg/m(2)/day in 3 patients, 100 mg/m(2)/day in 7 + 11(#) patients, and 125 mg/m(2)/day in 7 patients. Three (17.6%) patients in phase I experienced a dose limiting toxicity (DLT), all at the 125 mg/m(2)/day dose level, establishing the lower dose of 100 mg/m(2)/day as the RD. The DLTs were neutropenia grade 4 according to the Common Terminology Criteria for Adverse Events (CTCAE) and thrombocytopenia grade 4 (2 patients), and vomiting grade 2 with hospitalisation and hypokalaemia grade 3 (1 patient). The best response was a clinically meaningful stabilization observed in 3 patients. In two of them, the disease stabilization exceeded the previous platinum-free interval (PFI).
  
  
  CONCLUSIONS
  The RD for elacytarabine was 100 mg/m(2)/day, D1-5 and D8-12 q4w. The safety profile was comparable to the safety profiles reported in previous clinical studies with elacytarabine in solid tumours. Despite some longer-lasting disease stabilisations, two of them exceeding the previous progression-free interval, further investigations of elacytarabine in the ovarian cancer indication are not warranted.
authors: Istituto Nazionale Tumori, IRCCS Fondazione G. Pascale, Naples, EU, Italy. s.pignata@istitutotumori.na.it
authors: S
authors: S
authors: Pignata
authors: F
authors: F
authors: Amant
authors: G
authors: G
authors: Scambia
authors: R
authors: R
authors: Sorio
authors: E
authors: E
authors: Breda
authors: W
authors: W
authors: Rasch
authors: K
authors: K
authors: Hernes
authors: C
authors: C
authors: Pisano
authors: K
authors: K
authors: Leunen
authors: D
authors: D
authors: Lorusso
authors: L
authors: L
authors: Cannella
authors: I
authors: I
authors: Vergote
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D003561:Cytarabine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy*
chemical_list: D000964:Antimetabolites, Antineoplastic; D003561:Cytarabine; C047645:5'-oleoyl cytarabine