title: Results of a phase I-II study of fenretinide and rituximab for patients with indolent B-cell lymphoma and mantle cell lymphoma.
abstract: Fenretinide, a synthetic retinoid, induces apoptotic cell death in B-cell non-Hodgkin lymphoma (B-NHL) and acts synergistically with rituximab in preclinical models. We report results from a phase I-II study of fenretinide with rituximab for B-NHLs. Eligible diagnoses included indolent B-NHL or mantle cell lymphoma. The phase I design de-escalated from fenretinide at 900 mg/m2PO BID for days 1-5 of a 7-day cycle. The phase II portion added 375 mg/m2IV rituximab weekly on weeks 5-9 then every 3 months. Fenretinide was continued until progression or intolerance. Thirty-two patients were treated: 7 in phase I, and 25 in phase II of the trial. No dose-limiting toxicities were observed. The phase II component utilized fenretinide 900 mg/m2twice daily with rituximab. The most common treatment-related adverse events of grade 3 or higher were rash (n = 3) and neutropenia (n = 3). Responses were seen in 6 (24%) patients on the phase II study, with a median duration of response of 47 months (95% confidence interval, 2-56). The combination of fenretinide and rituximab was well tolerated, yielded a modest overall response rate, but with prolonged remission durations. Further study should focus on identifying the responsive subset of B-NHL.
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.|Division of Medical Oncology, Department of Medicine, University of Washington, Seattle, WA, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Cowan
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: Phillip A
authors.initials: PA
authors.lastname: Stevenson
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: Ted A
authors.initials: TA
authors.lastname: Gooley
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: Shani L
authors.initials: SL
authors.lastname: Frayo
authors.affiliation: Department of Radiology, Harvard Medical School, MGH Hospital, Boston, MA, USA.
authors.forename: George R
authors.initials: GR
authors.lastname: Oliveira
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.|Division of Medical Oncology, Department of Medicine, University of Washington, Seattle, WA, USA.
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Smith
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.|Division of Medical Oncology, Department of Medicine, University of Washington, Seattle, WA, USA.
authors.forename: Damian J
authors.initials: DJ
authors.lastname: Green
authors.affiliation: Division of Medical Oncology, Department of Medicine, University of Washington, Seattle, WA, USA.
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Roden
authors.affiliation: Swedish Cancer Institute, Seattle, WA, USA.
authors.forename: John M
authors.initials: JM
authors.lastname: Pagel
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.|Division of Hematopathology, Department of Laboratory Medicine, University of Washington, Seattle, WA, USA.
authors.forename: Brent L
authors.initials: BL
authors.lastname: Wood
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.|Division of Medical Oncology, Department of Medicine, University of Washington, Seattle, WA, USA.
authors.forename: Oliver W
authors.initials: OW
authors.lastname: Press
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.|Division of Medical Oncology, Department of Medicine, University of Washington, Seattle, WA, USA.
authors.forename: Ajay K
authors.initials: AK
authors.lastname: Gopal
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D004357:Drug Synergism; D005076:Exanthema / Q000139:chemically induced; D005260:Female; D017313:Fenretinide / Q000008:administration & dosage*; D006801:Humans; D016393:Lymphoma, B-Cell / Q000150:complications / Q000188:drug therapy*; D020522:Lymphoma, Mantle-Cell / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D012074:Remission Induction; D000069283:Rituximab / Q000008:administration & dosage*
chemical_list: D017313:Fenretinide; D000069283:Rituximab
keywords: 4HPR; B cell lymphoma; fenretinide; indolent lymphoma; retinoids