title: A randomized, double-blind, placebo-controlled, phase II study comparing the tolerability and efficacy of ipilimumab administered with or without prophylactic budesonide in patients with unresectable stage III or IV melanoma.
abstract: OBJECTIVE
  Diarrhea (with or without colitis) is an immune-related adverse event (irAE) associated with ipilimumab. A randomized, double-blind, placebo-controlled, multicenter, multinational phase II trial was conducted to determine whether prophylactic budesonide (Entocort EC), a nonabsorbed oral steroid, reduced the rate of grade >or=2 diarrhea in ipilimumab-treated patients with advanced melanoma.
  
  
  METHODS
  Previously treated and treatment-naïve patients (N = 115) with unresectable stage III or IV melanoma received open-label ipilimumab (10 mg/kg every 3 weeks for four doses) with daily blinded budesonide (group A) or placebo (group B) through week 16. The first scheduled tumor evaluation was at week 12; eligible patients received maintenance treatment starting at week 24. Diarrhea was assessed using Common Terminology Criteria for Adverse Events (CTCAE) 3.0. Patients kept a diary describing their bowel habits.
  
  
  RESULTS
  Budesonide did not affect the rate of grade >or=2 diarrhea, which occurred in 32.7% and 35.0% of patients in groups A and B, respectively. There were no bowel perforations or treatment-related deaths. Best overall response rates were 12.1% in group A and 15.8% in group B, with a median overall survival of 17.7 and 19.3 months, respectively. Within each group, the disease control rate was higher in patients with grade 3 to 4 irAEs than in patients with grade 0 to 2 irAEs, although many patients with grade 1 to 2 irAEs experienced clinical benefit. Novel patterns of response to ipilimumab were observed.
  
  
  CONCLUSIONS
  Ipilimumab shows activity in advanced melanoma, with encouraging survival and manageable adverse events. Budesonide should not be used prophylactically for grade >or=2 diarrhea associated with ipilimumab therapy.
authors: Moffitt Cancer Center, Tampa, Florida 33612, USA. Jeffrey.Weber@moffitt.org
authors: Jeffrey
authors: J
authors: Weber
authors: John A
authors: JA
authors: Thompson
authors: Omid
authors: O
authors: Hamid
authors: David
authors: D
authors: Minor
authors: Asim
authors: A
authors: Amin
authors: Ilan
authors: I
authors: Ron
authors: Ruggero
authors: R
authors: Ridolfi
authors: Hazem
authors: H
authors: Assi
authors: Anthony
authors: A
authors: Maraveyas
authors: David
authors: D
authors: Berman
authors: Jonathan
authors: J
authors: Siegel
authors: Steven J
authors: SJ
authors: O'Day
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols; D019819:Budesonide / Q000008:administration & dosage*; D003967:Diarrhea / Q000139:chemically induced / Q000188:drug therapy; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D000074324:Ipilimumab; D053208:Kaplan-Meier Estimate; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D008875:Middle Aged; D009367:Neoplasm Staging; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D000074324:Ipilimumab; D019819:Budesonide