title: Pharmacokinetics and safety of subcutaneous rituximab plus fludarabine and cyclophosphamide for patients with chronic lymphocytic leukaemia.
abstract: OBJECTIVE
  The aim of the phase Ib, two part SAWYER study (BO25341; NCT01292603) was to investigate the pharmacokinetics and safety of subcutaneous (s.c.) rituximab compared with intravenous (i.v.) rituximab, both in combination with fludarabine and cyclophosphamide (FC), as first line treatment for patients with chronic lymphocytic leukaemia (CLL).
  
  
  METHODS
  During part 1 (dose-finding), CLL patients received rituximab i.v. followed by a single dose of rituximab s.c. at one of three fixed doses (1400, 1600 or 1870 mg) in cycle 6. The primary objective was to identify a fixed s.c. dose that would achieve comparable rituximab serum trough concentrations (Ctrough ) to those achieved with the standard 4 weekly 500 mg m(-2) rituximab i.v. dose.
  
  
  RESULTS
  Fifty-five patients received a fixed dose of rituximab s.c., 16 received 1400 mg, 17 received 1600 mg and 22 received 1870 mg. The 1600 mg dose was predicted to achieve non-inferior Ctrough to standard rituximab i.v.
  
  
  METHODS
  The rituximab s.c. safety profile was comparable with rituximab i.v., except that local administration-related reactions, mainly mild/moderate injection site reactions, occurred more frequently with rituximab s.c., which was not unexpected. Subcutaneous administration was preferred to i.v. administration by >90% of patients and nurses (n = 112).
  
  
  CONCLUSIONS
  SAWYER part 1 data predict that rituximab s.c. 1600 mg will achieve non-inferior Ctrough concentrations to rituximab i.v. 500 mg m(-2) , administered 4 weekly. This fixed s.c. dose is currently undergoing formal non-inferiority assessment in SAWYER part 2. In future, CLL treatment regimens comprising rituximab s.c. and oral FC could substantially reduce i.v. chair time.
authors.affiliation: Jewish General Hospital, Montreal, Canada.
authors.forename: Sarit
authors.initials: S
authors.lastname: Assouline
authors.affiliation: Hematology Division, Hospital das Clinicas da Faculdade de Medicina da Universidade de Săo Paulo, Săo Paulo, Brazil.
authors.forename: Valeria
authors.initials: V
authors.lastname: Buccheri
authors.affiliation: Hematologie Clinique, Hôpital Robert Debré, Reims, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Delmer
authors.affiliation: Division of Hematology, Department of Translational Medicine, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Gaidano
authors.affiliation: Roche Products Ltd, Welwyn Garden City, UK.
authors.forename: Christine
authors.initials: C
authors.lastname: McIntyre
authors.affiliation: Roche Products Ltd, Welwyn Garden City, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Brewster
authors.affiliation: F. Hoffmann-La Roche Ltd, Basel, Switzerland.
authors.forename: Olivier
authors.initials: O
authors.lastname: Catalani
authors.affiliation: F. Hoffmann-La Roche Ltd, Basel, Switzerland.
authors.forename: Florence
authors.initials: F
authors.lastname: Hourcade-Potelleret
authors.affiliation: F. Hoffmann-La Roche Ltd, Basel, Switzerland.
authors.forename: Pakeeza
authors.initials: P
authors.lastname: Sayyed
authors.affiliation: Department of Haematology, St. George Hospital, Kogarah, Australia.
authors.forename: Xavier
authors.initials: X
authors.lastname: Badoux
mesh_terms: D061605:Administration, Intravenous; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D003520:Cyclophosphamide / Q000008:administration & dosage* / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D057240:Patient Preference; D000069283:Rituximab / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000069283:Rituximab; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine
keywords: chronic lymphocytic leukaemia; cyclophosphamide; fludarabine; pharmacokinetics; rituximab; subcutaneous