title: Megestrol acetate versus metronomic cyclophosphamide in patients having exhausted all effective therapies under standard care.
abstract: BACKGROUND
  To evaluate the antitumour activity and safety of metronomic cyclophosphamide vs megestrol acetate in progressive and advanced cancer patients having exhausted all effective therapies under standard care.
  
  
  METHODS
  Patients were randomly assigned to receive orally metronomic cyclophosphamide (50 mg b.i.d) or megestrol acetate (160 mg only daily) until intolerance or progression (RECIST 1.0). The primary efficacy end point was a 2-month progression-free rate (PFR(2m)). According to Optimal Simon's design and the following assumptions, namely, P0=5%, P1=20%, alpha=beta=10%, the treatment is considered as effective if atleast 5 out of 44 patients achieved PFR(2m).
  
  
  RESULTS
  Between September 2006 and January 2009, 88 patients were enrolled. Two patients experienced grade 3-4 toxicities in each arm (4%). One toxic death occurred in the megestrol acetate arm as a consequence of thrombosis. The metronomic cyclophosphamide arm reached the predefined level of efficacy with a PFR(2m) rate of 9 out of 44 and a PFR(4m) rate of 5 out of 44. The MA arm failed to achieve the level of efficacy with a PFR(2m) of 4 out of 44 and a PFR(4m) of 1 out of 44. The median overall survival was 195 and 144 days in the metronomic cyclophosphamide arm and megestrol acetate arm, respectively.
  
  
  CONCLUSIONS
  Metronomic cyclophosphamide is well tolerated and provides stable disease in such vulnerable and poor-prognosis cancer patients. This regimen warrants further evaluations.
authors.affiliation: Centre Oscar Lambret, Lille, France. n-penel@o-lambret.fr
authors.forename: N
authors.initials: N
authors.lastname: Penel
authors.forename: S
authors.initials: S
authors.lastname: Clisant
authors.forename: E
authors.initials: E
authors.lastname: Dansin
authors.forename: C
authors.initials: C
authors.lastname: Desauw
authors.forename: M
authors.initials: M
authors.lastname: Dégardin
authors.forename: L
authors.initials: L
authors.lastname: Mortier
authors.forename: M
authors.initials: M
authors.lastname: Vanhuyse
authors.forename: F
authors.initials: F
authors.lastname: Bonodeau
authors.forename: C
authors.initials: C
authors.lastname: Fournier
authors.forename: J-L
authors.initials: JL
authors.lastname: Cazin
authors.forename: A
authors.initials: A
authors.lastname: Adenis
mesh_terms: D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage*; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage* / Q000009:adverse effects; D018450:Disease Progression; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D008297:Male; D019290:Megestrol Acetate / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000401:mortality; D010166:Palliative Care
chemical_list: D018906:Antineoplastic Agents, Alkylating; D018931:Antineoplastic Agents, Hormonal; D003520:Cyclophosphamide; D019290:Megestrol Acetate