Monday, November 10, 2008
Journal of Clinical Oncology has a double-blind, placebo-controlled trial of depot octreotide for the prevention of radiation-induced diarrhea. (The context here is that octreotide has some good trial data supporting its use to treat radiation-induced diarrhea.) This study involved 125 patients receiving radiation involving the entire pelvis (for a variety of malignancies); they received 20mg depot octreotide or placebo at enrollment and after 29 days. The study was powered at 85% to detect a 1-grade difference in diarrhea severity between groups.
It didn't look very good for octreotide. Diarrhea outcomes were essentially identical (incidence and severity) and the octreotide group had more adverse events (no biliary toxicity, but symptoms of GI cramping and constipation-like symptoms). Incidence of moderate to severe diarrhea was in the 20-30% range overall.
This study was done well enough that it's pretty safe to conclude that depot ocreotide is, indeed, worthless to prevent acute radiation associated diarrhea, and has signficant side effects. Given that there are some ok data for short-acting octreotide to treat diarrhea once it starts, I'm unsure whether this is an effect of depot octreotide itself or (more likely) simply a matter that the incidence of acute radiation induced diarrhea is low enough that prophylaxing for it with a drug with significant toxicities is just not worth it. Or both. Severe enteritis from radiation, while relatively rare, can be such a devastating and morbid complication (fecal incontinence, hospitalizations for hypovolemia, disruption in cancer therapy) that it's disappointing this didn't pan out....
J. A. Martenson, M. Y. Halyard, J. A. Sloan, G. M. Proulx, R. C. Miller, R. L. Deming, S. J. Dick, H. A. Johnson, T.H. P. Tai, A. W. Zhu, J. Keit, K. J. Stien, P. J. Atherton (2008). Phase III, Double-Blind Study of Depot Octreotide Versus Placebo in the Prevention of Acute Diarrhea in Patients Receiving Pelvic Radiation Therapy: Results of North Central Cancer Treatment Group N00CA Journal of Clinical Oncology, 26 (32), 5248-5253 DOI: 10.1200/JCO.2008.17.1546