Zachariah, B., Gwede, C.K., James, J., Ajani, J., Chin, L.J., Donath, D., … Kachnic, L.A. (2010). Octreotide acetate in prevention of chemoradiation-induced diarrhea in anorectal cancer: Randomized RTOG trial 0315. Journal of the National Cancer Institute, 102(8), 547-556.

To assess the ability of long-acting octerotide (LAO) to prevent acute diarrhea in patients undergoing concurrent chemoradiation for rectal or anal cancer

Patients were randomized to either receive two 30 mg intramuscular injections of LAO or placebo. A “test” dose of 100 µg LAO was administered. Patients who tolerated the test dose then received a 30-mg dose of study drug between days 4–7 before the start of radiation and a second dose on day 22 (+ 3 days) of radiation. Patients received concurrent chemotherapy and radiation therapy to the pelvis. Radiation and chemotherapy regimens varied by institution. The plan was for a minimal dose of 45 Gy with a portal of 10x10 cm to the whole pelvis and a boost to the tumor bed. Follow-up evaluations were performed 3, 6, 9, and 15 months from start of radiation therapy.

• The study reported on 215 patients.
• The mean age of patients in the LAO group was 61 years with a range of 27–83 years. The mean age of patients in the placebo group was 61 years with a range of 37–85 years.
• The LAO sample was 38% female and 62% male. The placebo group was 36% female and 64% male.
• The majority (80%) of patients had rectal cancer.

The study was conducted at multiple outpatient settings in the United States.

Patients were undergoing the active treatment phase of care.

This was a randomized, double-blinded, placebo-controlled trial.

The National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (version 3.0) (CTCAE), Qualify of Life–Radiation Therapy Instrument (QOL-RTI), 14-item Expanded Prostate Cancer Index (EPIC)–Bowel, 7-item Functional Alterations due to Changes in Elimination–Bowel (FACE-Bowel), and 4-item Diarrhea Assessment Scale (DAS) were used.

• Prophylactic use of LAO is not beneficial in reducing the severity or preventing the incidence of diarrhea in patients receiving concurrent chemotherapy and radiation therapy for rectal or anal cancer.
• Incidence of grade 2–4 acute diarrhea was similar in both groups (49% in the placebo group versus 44% in the LAO group).
• LAO did not reduce the number of hospitalizations required (p = 0.55) or eliminate the need for additional standard antidiarrheal agents (p = 0.67).
• LAO did not prevent modifications, delays, or interruptions in chemotherapy (p = 0.27) or radiation therapy (p = 0.95).

LAO did not demonstrate a statistically significant reduction in the incidence or severity of diarrhea or change in patient-reported bowel function and QOL in patients with rectal or anal cancer undergoing chemotherapy and radiation therapy.

• No intention-to-treat analysis was performed.
• This study had a short follow-up timeframe with a median follow-up of only 9.64 months. Further long-term assessment should be conducted to evaluate QOL.

More clinical research is needed to evaluate interventions for the prevention of diarrhea in patients receiving chemotherapy and radiation therapy concurrently for rectal or anal cancer. LAO does not appear to reduce the incidence or severity of diarrhea or change patient-reported bowel function or QOL. Other studies have reported similar results. LAO should not be used to prevent diarrhea in patients receiving combined chemotherapy and radiation therapy outside of a controlled clinical research setting.