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. Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] Journal article | | 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. | | Author(s) | Weber J, Thompson JA, Hamid O, Minor D, Amin A, Ron I, Ridolfi R, Assi H, Maraveyas A, Berman D, Siegel J, O'Day SJ | | Institution | Authors' Affiliations: Moffitt Cancer Center, Tampa, Florida; Seattle Cancer Care Alliance, University of Washington, Seattle, Washington; The Angeles Clinic and Research Institute, Santa Monica, California; California Pacific Medical Center, San Francisco Oncology Associates, San Francisco, California; Blumenthal Cancer Center, Charlotte, North Carolina; Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola, Italy; Department of Internal Medicine, The Moncton Hospital, Moncton, New Brunswick, Canada; Castle Hill Hospital, Hull, United Kingdom; and Bristol-Myers Squibb, Lawrenceville, New Jersey. | | Source | Clin Cancer Res 2009 Aug 11. | | Abstract | PURPOSE: 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 >/=2 diarrhea in ipilimumab-treated patients with advanced melanoma. EXPERIMENTAL
DESIGN: 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 >/=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 >/=2 diarrhea associated with ipilimumab therapy. (Clin Cancer Res 2009;15(17):OF1-8). | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19671877 |
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