RTOG 0315: A randomized, double-blind, placebo-controlled phase III study to determine the efficacy of octreotide acetate in preventing or reducing the severity of chemoradiation-induced diarrhea in patients with anal or rectal cancer

Abstract

4032 Background: Diarrhea is a common side effect of chemoradiation for pelvic malignancies. Octreotide acetate has been shown to control grade 3–4 chemotherapy-induced diarrhea in >90% of patients. The primary objective of this randomized placebo-controlled phase III study was to determine the efficacy of long acting octreotide acetate in preventing the onset of grade 2–4 diarrhea. Secondary objectives were to assess the impact of diarrhea on chemoradiation delivery and medical resource utilization. Methods: Eligible patients (pts) with primary anal or rectal cancer, and scheduled to receive concurrent chemoradiation to a minimum dose of 45 Gy using pelvic field sizes greater than 10x10cm, were enrolled. Pts with history of pelvic radiotherapy, chronic bowel disease, diarrhea of grade ≥2, or colostomy were excluded from the study. Pts were stratified by RT dose (<50 Gy and ≥50 Gy), chemotherapy (bolus and continuous) and gender. Pts were randomized to receive two 30 mg intramuscular injections of octreotide acetate (Sandostatin LAR® Depot) or placebo. Injections were given between day -7 and day -4 and on day 22 (± 3 days) of RT. The primary endpoint was incidence of grade 2, 3, or 4 diarrhea (CTCAE v3.0). Assuming a 45% placebo incidence rate, a one-sided chi-square test (alpha 0.05) would require 226 pts to detect a 42% reduction in incidence due to octreotide acetate. Results: The study accrued 233 pts (215 analyzable), 106 pts in the placebo arm and 109 pts in the octreotide acetate arm. The majority of pts (80%) on each arm had rectal cancer. There was no statistically significant difference in incidence of grade 2+ diarrhea (p=0.21) with 52 (49%) and 48 (44%) in the placebo and octreotide acetate treatment arms, respectively. There was also no statistically significant difference between the treatment arms in chemoradiation delivery or medical resource utilization. Conclusions: Prophylactic use of octreotide acetate was not shown to significantly reduce the incidence of mild, moderate or severe diarrhea. No significant financial relationships to disclose.