title: Rituximab extended schedule or re-treatment trial for low-tumor burden follicular lymphoma: eastern cooperative oncology group protocol e4402.
abstract: OBJECTIVE
  In low-tumor burden follicular lymphoma (FL), maintenance rituximab (MR) has been shown to improve progression-free survival when compared with observation. It is not known whether MR provides superior long-term disease control compared with re-treatment rituximab (RR) administered on an as-needed basis. E4402 (RESORT) was a randomized clinical trial designed to compare MR against RR.
  
  
  METHODS
  Eligible patients with previously untreated low-tumor burden FL received four doses of rituximab, and responding patients were randomly assigned to either RR or MR. Patients receiving RR were eligible for re-treatment at each disease progression until treatment failure. Patients assigned to MR received a single dose of rituximab every 3 months until treatment failure. The primary end point was time to treatment failure. Secondary end points included time to first cytotoxic therapy, toxicity, and health-related quality of life (HRQOL).
  
  
  RESULTS
  A total of 289 patients were randomly assigned to RR or MR. With a median follow-up of 4.5 years, the estimated median time to treatment failure was 3.9 years for patients receiving RR and 4.3 years for those receiving MR (P = .54). Three-year freedom from cytotoxic therapy was 84% for those receiving RR and 95% for those receiving MR (P = .03). The median number of rituximab doses was four patients receiving RR and 18 for those receiving MR. There was no difference in HRQOL. Grade 3 to 4 toxicities were infrequent in both arms.
  
  
  CONCLUSIONS
  In low-tumor burden FL, a re-treatment strategy uses less rituximab while providing disease control comparable to that achieved with a maintenance strategy.
authors.affiliation: Brad S. Kahl, University of Wisconsin, Madison; Christopher G. Peterson, Aspirus Regional Cancer Center, Wausau; Matthias Weiss, Marshfield Clinic, Marshfield, WI; Fangxin Hong, Dana-Farber Cancer Institute, Boston, MA; Michael E. Williams, University of Virginia, Charlottesville, VA; Randy D. Gascoyne, British Columbia Cancer Agency, Vancouver, British Columbia, Canada; Lynne I. Wagner, Northwestern University, Chicago, IL; John C. Krauss, University of Michigan, Ann Arbor, MI; Thomas M. Habermann, Mayo Clinic, Rochester; Mark D. Sborov, Fairview-Southdale Hospital, St Louis Park, MN; Lode J. Swinnen, Johns Hopkins University, Baltimore, MD; Stephen J. Schuster, University of Pennsylvania, Philadelphia; W. Christopher Ehmann, Penn State Cancer Institute, Hershey, PA; S. Eric Martin, Christiana Care Community Clinical Oncology Program and Helen F. Graham Cancer Network, Newark, DE; and Sandra J. Horning, Genentech, South San Francisco, CA. bsk@medicine.wisc.edu.
authors.forename: Brad S
authors.initials: BS
authors.lastname: Kahl
authors.affiliation: Brad S. Kahl, University of Wisconsin, Madison; Christopher G. Peterson, Aspirus Regional Cancer Center, Wausau; Matthias Weiss, Marshfield Clinic, Marshfield, WI; Fangxin Hong, Dana-Farber Cancer Institute, Boston, MA; Michael E. Williams, University of Virginia, Charlottesville, VA; Randy D. Gascoyne, British Columbia Cancer Agency, Vancouver, British Columbia, Canada; Lynne I. Wagner, Northwestern University, Chicago, IL; John C. Krauss, University of Michigan, Ann Arbor, MI; Thomas M. Habermann, Mayo Clinic, Rochester; Mark D. Sborov, Fairview-Southdale Hospital, St Louis Park, MN; Lode J. Swinnen, Johns Hopkins University, Baltimore, MD; Stephen J. Schuster, University of Pennsylvania, Philadelphia; W. Christopher Ehmann, Penn State Cancer Institute, Hershey, PA; S. Eric Martin, Christiana Care Community Clinical Oncology Program and Helen F. Graham Cancer Network, Newark, DE; and Sandra J. Horning, Genentech, South San Francisco, CA.
authors.forename: Fangxin
authors.initials: F
authors.lastname: Hong
authors.affiliation: Brad S. Kahl, University of Wisconsin, Madison; Christopher G. Peterson, Aspirus Regional Cancer Center, Wausau; Matthias Weiss, Marshfield Clinic, Marshfield, WI; Fangxin Hong, Dana-Farber Cancer Institute, Boston, MA; Michael E. Williams, University of Virginia, Charlottesville, VA; Randy D. Gascoyne, British Columbia Cancer Agency, Vancouver, British Columbia, Canada; Lynne I. Wagner, Northwestern University, Chicago, IL; John C. Krauss, University of Michigan, Ann Arbor, MI; Thomas M. Habermann, Mayo Clinic, Rochester; Mark D. Sborov, Fairview-Southdale Hospital, St Louis Park, MN; Lode J. Swinnen, Johns Hopkins University, Baltimore, MD; Stephen J. Schuster, University of Pennsylvania, Philadelphia; W. Christopher Ehmann, Penn State Cancer Institute, Hershey, PA; S. Eric Martin, Christiana Care Community Clinical Oncology Program and Helen F. Graham Cancer Network, Newark, DE; and Sandra J. Horning, Genentech, South San Francisco, CA.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Williams
authors.affiliation: Brad S. Kahl, University of Wisconsin, Madison; Christopher G. Peterson, Aspirus Regional Cancer Center, Wausau; Matthias Weiss, Marshfield Clinic, Marshfield, WI; Fangxin Hong, Dana-Farber Cancer Institute, Boston, MA; Michael E. Williams, University of Virginia, Charlottesville, VA; Randy D. Gascoyne, British Columbia Cancer Agency, Vancouver, British Columbia, Canada; Lynne I. Wagner, Northwestern University, Chicago, IL; John C. Krauss, University of Michigan, Ann Arbor, MI; Thomas M. Habermann, Mayo Clinic, Rochester; Mark D. Sborov, Fairview-Southdale Hospital, St Louis Park, MN; Lode J. Swinnen, Johns Hopkins University, Baltimore, MD; Stephen J. Schuster, University of Pennsylvania, Philadelphia; W. Christopher Ehmann, Penn State Cancer Institute, Hershey, PA; S. Eric Martin, Christiana Care Community Clinical Oncology Program and Helen F. Graham Cancer Network, Newark, DE; and Sandra J. Horning, Genentech, South San Francisco, CA.
authors.forename: Randy D
authors.initials: RD
authors.lastname: Gascoyne
authors.affiliation: Brad S. Kahl, University of Wisconsin, Madison; Christopher G. Peterson, Aspirus Regional Cancer Center, Wausau; Matthias Weiss, Marshfield Clinic, Marshfield, WI; Fangxin Hong, Dana-Farber Cancer Institute, Boston, MA; Michael E. Williams, University of Virginia, Charlottesville, VA; Randy D. Gascoyne, British Columbia Cancer Agency, Vancouver, British Columbia, Canada; Lynne I. Wagner, Northwestern University, Chicago, IL; John C. Krauss, University of Michigan, Ann Arbor, MI; Thomas M. Habermann, Mayo Clinic, Rochester; Mark D. Sborov, Fairview-Southdale Hospital, St Louis Park, MN; Lode J. Swinnen, Johns Hopkins University, Baltimore, MD; Stephen J. Schuster, University of Pennsylvania, Philadelphia; W. Christopher Ehmann, Penn State Cancer Institute, Hershey, PA; S. Eric Martin, Christiana Care Community Clinical Oncology Program and Helen F. Graham Cancer Network, Newark, DE; and Sandra J. Horning, Genentech, South San Francisco, CA.
authors.forename: Lynne I
authors.initials: LI
authors.lastname: Wagner
authors.affiliation: Brad S. Kahl, University of Wisconsin, Madison; Christopher G. Peterson, Aspirus Regional Cancer Center, Wausau; Matthias Weiss, Marshfield Clinic, Marshfield, WI; Fangxin Hong, Dana-Farber Cancer Institute, Boston, MA; Michael E. Williams, University of Virginia, Charlottesville, VA; Randy D. Gascoyne, British Columbia Cancer Agency, Vancouver, British Columbia, Canada; Lynne I. Wagner, Northwestern University, Chicago, IL; John C. Krauss, University of Michigan, Ann Arbor, MI; Thomas M. Habermann, Mayo Clinic, Rochester; Mark D. Sborov, Fairview-Southdale Hospital, St Louis Park, MN; Lode J. Swinnen, Johns Hopkins University, Baltimore, MD; Stephen J. Schuster, University of Pennsylvania, Philadelphia; W. Christopher Ehmann, Penn State Cancer Institute, Hershey, PA; S. Eric Martin, Christiana Care Community Clinical Oncology Program and Helen F. Graham Cancer Network, Newark, DE; and Sandra J. Horning, Genentech, South San Francisco, CA.
authors.forename: John C
authors.initials: JC
authors.lastname: Krauss
authors.affiliation: Brad S. Kahl, University of Wisconsin, Madison; Christopher G. Peterson, Aspirus Regional Cancer Center, Wausau; Matthias Weiss, Marshfield Clinic, Marshfield, WI; Fangxin Hong, Dana-Farber Cancer Institute, Boston, MA; Michael E. Williams, University of Virginia, Charlottesville, VA; Randy D. Gascoyne, British Columbia Cancer Agency, Vancouver, British Columbia, Canada; Lynne I. Wagner, Northwestern University, Chicago, IL; John C. Krauss, University of Michigan, Ann Arbor, MI; Thomas M. Habermann, Mayo Clinic, Rochester; Mark D. Sborov, Fairview-Southdale Hospital, St Louis Park, MN; Lode J. Swinnen, Johns Hopkins University, Baltimore, MD; Stephen J. Schuster, University of Pennsylvania, Philadelphia; W. Christopher Ehmann, Penn State Cancer Institute, Hershey, PA; S. Eric Martin, Christiana Care Community Clinical Oncology Program and Helen F. Graham Cancer Network, Newark, DE; and Sandra J. Horning, Genentech, South San Francisco, CA.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Habermann
authors.affiliation: Brad S. Kahl, University of Wisconsin, Madison; Christopher G. Peterson, Aspirus Regional Cancer Center, Wausau; Matthias Weiss, Marshfield Clinic, Marshfield, WI; Fangxin Hong, Dana-Farber Cancer Institute, Boston, MA; Michael E. Williams, University of Virginia, Charlottesville, VA; Randy D. Gascoyne, British Columbia Cancer Agency, Vancouver, British Columbia, Canada; Lynne I. Wagner, Northwestern University, Chicago, IL; John C. Krauss, University of Michigan, Ann Arbor, MI; Thomas M. Habermann, Mayo Clinic, Rochester; Mark D. Sborov, Fairview-Southdale Hospital, St Louis Park, MN; Lode J. Swinnen, Johns Hopkins University, Baltimore, MD; Stephen J. Schuster, University of Pennsylvania, Philadelphia; W. Christopher Ehmann, Penn State Cancer Institute, Hershey, PA; S. Eric Martin, Christiana Care Community Clinical Oncology Program and Helen F. Graham Cancer Network, Newark, DE; and Sandra J. Horning, Genentech, South San Francisco, CA.
authors.forename: Lode J
authors.initials: LJ
authors.lastname: Swinnen
authors.affiliation: Brad S. Kahl, University of Wisconsin, Madison; Christopher G. Peterson, Aspirus Regional Cancer Center, Wausau; Matthias Weiss, Marshfield Clinic, Marshfield, WI; Fangxin Hong, Dana-Farber Cancer Institute, Boston, MA; Michael E. Williams, University of Virginia, Charlottesville, VA; Randy D. Gascoyne, British Columbia Cancer Agency, Vancouver, British Columbia, Canada; Lynne I. Wagner, Northwestern University, Chicago, IL; John C. Krauss, University of Michigan, Ann Arbor, MI; Thomas M. Habermann, Mayo Clinic, Rochester; Mark D. Sborov, Fairview-Southdale Hospital, St Louis Park, MN; Lode J. Swinnen, Johns Hopkins University, Baltimore, MD; Stephen J. Schuster, University of Pennsylvania, Philadelphia; W. Christopher Ehmann, Penn State Cancer Institute, Hershey, PA; S. Eric Martin, Christiana Care Community Clinical Oncology Program and Helen F. Graham Cancer Network, Newark, DE; and Sandra J. Horning, Genentech, South San Francisco, CA.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Schuster
authors.affiliation: Brad S. Kahl, University of Wisconsin, Madison; Christopher G. Peterson, Aspirus Regional Cancer Center, Wausau; Matthias Weiss, Marshfield Clinic, Marshfield, WI; Fangxin Hong, Dana-Farber Cancer Institute, Boston, MA; Michael E. Williams, University of Virginia, Charlottesville, VA; Randy D. Gascoyne, British Columbia Cancer Agency, Vancouver, British Columbia, Canada; Lynne I. Wagner, Northwestern University, Chicago, IL; John C. Krauss, University of Michigan, Ann Arbor, MI; Thomas M. Habermann, Mayo Clinic, Rochester; Mark D. Sborov, Fairview-Southdale Hospital, St Louis Park, MN; Lode J. Swinnen, Johns Hopkins University, Baltimore, MD; Stephen J. Schuster, University of Pennsylvania, Philadelphia; W. Christopher Ehmann, Penn State Cancer Institute, Hershey, PA; S. Eric Martin, Christiana Care Community Clinical Oncology Program and Helen F. Graham Cancer Network, Newark, DE; and Sandra J. Horning, Genentech, South San Francisco, CA.
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Peterson
authors.affiliation: Brad S. Kahl, University of Wisconsin, Madison; Christopher G. Peterson, Aspirus Regional Cancer Center, Wausau; Matthias Weiss, Marshfield Clinic, Marshfield, WI; Fangxin Hong, Dana-Farber Cancer Institute, Boston, MA; Michael E. Williams, University of Virginia, Charlottesville, VA; Randy D. Gascoyne, British Columbia Cancer Agency, Vancouver, British Columbia, Canada; Lynne I. Wagner, Northwestern University, Chicago, IL; John C. Krauss, University of Michigan, Ann Arbor, MI; Thomas M. Habermann, Mayo Clinic, Rochester; Mark D. Sborov, Fairview-Southdale Hospital, St Louis Park, MN; Lode J. Swinnen, Johns Hopkins University, Baltimore, MD; Stephen J. Schuster, University of Pennsylvania, Philadelphia; W. Christopher Ehmann, Penn State Cancer Institute, Hershey, PA; S. Eric Martin, Christiana Care Community Clinical Oncology Program and Helen F. Graham Cancer Network, Newark, DE; and Sandra J. Horning, Genentech, South San Francisco, CA.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Sborov
authors.affiliation: Brad S. Kahl, University of Wisconsin, Madison; Christopher G. Peterson, Aspirus Regional Cancer Center, Wausau; Matthias Weiss, Marshfield Clinic, Marshfield, WI; Fangxin Hong, Dana-Farber Cancer Institute, Boston, MA; Michael E. Williams, University of Virginia, Charlottesville, VA; Randy D. Gascoyne, British Columbia Cancer Agency, Vancouver, British Columbia, Canada; Lynne I. Wagner, Northwestern University, Chicago, IL; John C. Krauss, University of Michigan, Ann Arbor, MI; Thomas M. Habermann, Mayo Clinic, Rochester; Mark D. Sborov, Fairview-Southdale Hospital, St Louis Park, MN; Lode J. Swinnen, Johns Hopkins University, Baltimore, MD; Stephen J. Schuster, University of Pennsylvania, Philadelphia; W. Christopher Ehmann, Penn State Cancer Institute, Hershey, PA; S. Eric Martin, Christiana Care Community Clinical Oncology Program and Helen F. Graham Cancer Network, Newark, DE; and Sandra J. Horning, Genentech, South San Francisco, CA.
authors.forename: S Eric
authors.initials: SE
authors.lastname: Martin
authors.affiliation: Brad S. Kahl, University of Wisconsin, Madison; Christopher G. Peterson, Aspirus Regional Cancer Center, Wausau; Matthias Weiss, Marshfield Clinic, Marshfield, WI; Fangxin Hong, Dana-Farber Cancer Institute, Boston, MA; Michael E. Williams, University of Virginia, Charlottesville, VA; Randy D. Gascoyne, British Columbia Cancer Agency, Vancouver, British Columbia, Canada; Lynne I. Wagner, Northwestern University, Chicago, IL; John C. Krauss, University of Michigan, Ann Arbor, MI; Thomas M. Habermann, Mayo Clinic, Rochester; Mark D. Sborov, Fairview-Southdale Hospital, St Louis Park, MN; Lode J. Swinnen, Johns Hopkins University, Baltimore, MD; Stephen J. Schuster, University of Pennsylvania, Philadelphia; W. Christopher Ehmann, Penn State Cancer Institute, Hershey, PA; S. Eric Martin, Christiana Care Community Clinical Oncology Program and Helen F. Graham Cancer Network, Newark, DE; and Sandra J. Horning, Genentech, South San Francisco, CA.
authors.forename: Matthias
authors.initials: M
authors.lastname: Weiss
authors.affiliation: Brad S. Kahl, University of Wisconsin, Madison; Christopher G. Peterson, Aspirus Regional Cancer Center, Wausau; Matthias Weiss, Marshfield Clinic, Marshfield, WI; Fangxin Hong, Dana-Farber Cancer Institute, Boston, MA; Michael E. Williams, University of Virginia, Charlottesville, VA; Randy D. Gascoyne, British Columbia Cancer Agency, Vancouver, British Columbia, Canada; Lynne I. Wagner, Northwestern University, Chicago, IL; John C. Krauss, University of Michigan, Ann Arbor, MI; Thomas M. Habermann, Mayo Clinic, Rochester; Mark D. Sborov, Fairview-Southdale Hospital, St Louis Park, MN; Lode J. Swinnen, Johns Hopkins University, Baltimore, MD; Stephen J. Schuster, University of Pennsylvania, Philadelphia; W. Christopher Ehmann, Penn State Cancer Institute, Hershey, PA; S. Eric Martin, Christiana Care Community Clinical Oncology Program and Helen F. Graham Cancer Network, Newark, DE; and Sandra J. Horning, Genentech, South San Francisco, CA.
authors.forename: W Christopher
authors.initials: WC
authors.lastname: Ehmann
authors.affiliation: Brad S. Kahl, University of Wisconsin, Madison; Christopher G. Peterson, Aspirus Regional Cancer Center, Wausau; Matthias Weiss, Marshfield Clinic, Marshfield, WI; Fangxin Hong, Dana-Farber Cancer Institute, Boston, MA; Michael E. Williams, University of Virginia, Charlottesville, VA; Randy D. Gascoyne, British Columbia Cancer Agency, Vancouver, British Columbia, Canada; Lynne I. Wagner, Northwestern University, Chicago, IL; John C. Krauss, University of Michigan, Ann Arbor, MI; Thomas M. Habermann, Mayo Clinic, Rochester; Mark D. Sborov, Fairview-Southdale Hospital, St Louis Park, MN; Lode J. Swinnen, Johns Hopkins University, Baltimore, MD; Stephen J. Schuster, University of Pennsylvania, Philadelphia; W. Christopher Ehmann, Penn State Cancer Institute, Hershey, PA; S. Eric Martin, Christiana Care Community Clinical Oncology Program and Helen F. Graham Cancer Network, Newark, DE; and Sandra J. Horning, Genentech, South San Francisco, CA.
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: Horning
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D006801:Humans; D008224:Lymphoma, Follicular / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009503:Neutropenia / Q000139:chemically induced; D011379:Prognosis; D011788:Quality of Life; D019233:Retreatment; D000069283:Rituximab; D016896:Treatment Outcome; D047368:Tumor Burden / Q000187:drug effects*
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D000069283:Rituximab