Children’s International Polyposis (CHIP) study: a randomized, double-blind, placebo-controlled study of celecoxib in children with familial adenomatous polyposis

Abstract

ObjectiveTo evaluate the efficacy and safety of celecoxib versus placebo in the prevention and treatment of colorectal polyposis in children with familial adenomatous polyposis (FAP).MethodsIn this Phase III, double-blind, randomized, placebo-controlled, multicenter trial patients aged 10–17 years with FAP were randomized to celecoxib (16 mg/kg/day) or placebo for up to 5 years. Patients underwent annual assessments, including colonoscopies, to detect the time from randomization to the earliest occurrence of ≥20 polyps (>2 mm in size) or colorectal malignancy. The study was terminated early due to low rate of observed endpoints combined with a lower than expected enrollment rate. Descriptive results are provided.ResultsOf 106 randomized patients, 55 were treated with celecoxib (mean age 12.6 years; 52.7% female) and 51 were given placebo (mean age 12.2 years; 54.9% female). Disease progression (≥20 polyps, >2 mm in size) was observed in seven (12.7%) and 13 (25.5%) patients, respectively. The median time to disease progression was 2.1 years in the celecoxib group and 1.1 years for placebo. No patient developed colorectal cancer. The rate of adverse events (AEs) was similar in both groups (75.5% and 72.9%, respectively). Three patients in the celecoxib group (none in the placebo group) experienced serious AEs.ConclusionIn children with FAP, celecoxib was a well-tolerated treatment that was associated with a lower rate of colorectal polyposis and a longer time to disease progression compared with placebo. Due to the low rate of observed endpoints, the long-term impact of these results could not be ascertained.

Non-Steroidal Anti-Inflammatory Drugs in Colorectal Cancer Chemoprevention

“…Nevertheless, celecoxib 400 mg reduces the risk by over 30% [ 79 , 80 ]. The results of the CHIP study involving children with FAP also support the efficacy of celecoxib in reducing the risk of adenoma development, yet further studies on a larger population are needed to confirm these findings [ 81 ].…”

“…Therefore, the celecoxib therapy in young FAP patients associates with a decrease in the percentage of individuals who progressed with adenomatous polyposis and a delay in such progression. However, due to the small number of endpoints observed, it is not possible to determine what is the long-term effect of celecoxib therapy on polyp development in children with FAP [ 81 ].…”

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“…The potential of COX-2 as a therapeutic treatment has been investigated in multiple models of cancer. In fact, the COX-2 inhibitor, celecoxib, has been successful in the treatment of a specific type of colorectal cancer - familial adenomatous polyposis - in both adults and children [167,168] . Targeting COX-2 in breast cancer, by celecoxib or other NSAIDs, may inhibit tumor cell dissemination by reducing the expression of tumor-promotional collagen.…”

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“…Se ha demostrado que el uso de celecoxib y sulindac, reduce la formación de adenomas en pacientes con poliposis colónica familiar y disminuye la formación de adenomas colorrectales en pacientes con cáncer colorrectal esporádico (46). En niños con poliposis colónica familiar el tratamiento con celecoxib durante 5 años se asoció con menor tasa de poliposis y mayor tiempo de progresión de la enfermedad (52).…”