title: Solid malignancies among patients in the Wegener's Granulomatosis Etanercept Trial.
abstract: OBJECTIVE
  Etanercept is a soluble fusion protein designed to inhibit tumor necrosis factor (TNF). During the Wegener's Granulomatosis Etanercept Trial (WGET), a placebo-controlled trial of etanercept given in addition to standard therapy for remission induction and maintenance, more solid malignancies were observed in the etanercept group than in the group treated with standard therapy alone. This study was undertaken to further explore the potential association between anti-TNF therapy and the development of malignancy in these patients.
  
  
  METHODS
  One hundred eighty patients with active WG were enrolled and followed up for a median of 27 months. At enrollment, disease characteristics, treatment history, specific medical history items, and information about previous WG treatments and risk factors for malignancy were recorded. During the trial, the occurrence of malignancies and other adverse events was recorded prospectively.
  
  
  RESULTS
  All 6 solid malignancies observed during the WGET occurred in the etanercept group (P = 0.01 versus placebo group); based on a comparison of age- and sex-specific incidence rates, 1.92 solid malignancies would have been expected in this group. The solid malignancies included 2 cases of mucinous adenocarcinoma of the colon, 1 each of metastatic cholangiocarcinoma, renal cell carcinoma, and breast carcinoma, and 1 recurrent liposarcoma. There were no differences between the 2 treatment groups in sex distribution, disease severity, personal or family history of cancer, or tobacco and alcohol use. The etanercept group was older at baseline and less likely to be newly diagnosed with WG at the time of randomization. Patients who developed solid tumors were older than patients who did not. All etanercept-treated patients who developed solid tumors were also treated with cyclophosphamide during the trial. However, there were no differences between the groups in the amount of cyclophosphamide received during the trial or the percentage who had received cyclophosphamide before enrollment. There were also no differences in the mean duration of daily cyclophosphamide therapy or the maximum daily cyclophosphamide dosage before enrollment.
  
  
  CONCLUSIONS
  Data from the WGET, the first substantial reported experience of the combined use of etanercept and cyclophosphamide in the treatment of WG, indicate that the combination of TNF inhibition and cyclophosphamide may heighten the risk of cancer beyond that observed with cyclophosphamide alone.
authors.affiliation: Johns Hopkins University, Baltimore, Maryland, USA. jstone@jhmi.edu
authors.forename: John H
authors.initials: JH
authors.lastname: Stone
authors.forename: Janet T
authors.initials: JT
authors.lastname: Holbrook
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Marriott
authors.forename: Andrea K
authors.initials: AK
authors.lastname: Tibbs
authors.forename: Lourdes P
authors.initials: LP
authors.lastname: Sejismundo
authors.forename: Y-I
authors.initials: YI
authors.lastname: Min
authors.forename: Ulrich
authors.initials: U
authors.lastname: Specks
authors.forename: Peter A
authors.initials: PA
authors.lastname: Merkel
authors.forename: Robert
authors.initials: R
authors.lastname: Spiera
authors.forename: John C
authors.initials: JC
authors.lastname: Davis
authors.forename: E William
authors.initials: EW
authors.lastname: St Clair
authors.forename: W Joseph
authors.initials: WJ
authors.lastname: McCune
authors.forename: Steven R
authors.initials: SR
authors.lastname: Ytterberg
authors.forename: Nancy B
authors.initials: NB
authors.lastname: Allen
authors.forename: Gary S
authors.initials: GS
authors.lastname: Hoffman
mesh_terms: D000368:Aged; D002986:Clinical Trials as Topic; D000068800:Etanercept; D005260:Female; D014890:Granulomatosis with Polyangiitis / Q000188:drug therapy*; D006801:Humans; D007074:Immunoglobulin G / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000139:chemically induced*; D011446:Prospective Studies; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000068800:Etanercept