Probiotics Hold Promise for Preventing Radiation Enteropathy

TON - January 2017, Vol 10, No 1 - Supportive Care
Meg Barbor, MPH

Adelaide, Australia—Prophylactic probiotics can potentially prevent radiation enteropathy, according to research presented by Matthew A. Ciorba, MD, Assistant Professor of Medicine, Division of Gastroenterology, Washing­ton Uni­versity School of Medicine, St. Louis, MO, at the 2016 Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology Annual Meeting on Supportive Care in Cancer.

Probiotics are defined as live microbial organisms, most often bacteria, which confer beneficial effects to their host when consumed. “Ideally, if you can prevent the acute toxicities associated with radiation toxicity, you can then prevent the long-term consequences as well,” said Dr Ciorba. “Only a few published clinical trials have evaluated the relationship between probiotics and radiation injury, but radiation enteropathy is ideally suited for a probiotic intervention.”

Radiation Enteropathy and Ideal Gastrointestinal Protectants

Most patients with gastrointestinal (GI) cancers receive radiation as part of their therapy. Despite advances in radiotherapy, patients still experience collateral damage to the small intestine and remain at high risk for diarrheal complications after treatment. Therefore, new GI radioprotective agents are needed.

“Data suggest that the microbiota have the potential to modify the small intestinal response to radiation injury, and probiotic therapy could address the unmet need for intestinal radioprotectants,” he explained.

According to Dr Ciorba, probiotics are capable of addressing many of the attributes of a GI protectant. “Ideally, a GI radioprotectant will preserve the antitumor efficacy of radiation, and probiotics appear to have mostly local effects in the GI tract, so that goal is met with the use of a probiotic,” he said. Ideal GI protectants also offer wide tissue protection and a low toxicity profile, and probiotics are capable of coating the entire GI tract with few side effects.

Safe Use of Probiotics

“Patients and physicians are widely interested in natural approaches to preventing toxicities, and certainly probiotics fall in this category,” Dr Ciorba said. “What could be easier or more cost-effective than culturing some bacteria?” However, the potential for infection and negative antitumor effects must be considered, he said.

An understanding of the correct timing and dosage is also vital. People often think more is better, but some data suggest that this is not the case, said Dr Ciorba. “There should also be variation by therapy, so patients who receive radiation therapy in combination with fluoropyrimidine (5-FU) could have a very different toxicity profile and a very different response to probiotics than someone receiving radiation and cisplatin,” he cautioned.

Choice of Probiotic

Choosing the right probiotic is crucial, because preparations vary significantly. Probiotics may lack sufficient bacteria, contain dead bacteria, or offer the wrong species of bacteria, he added.

Dr Ciorba and his colleagues conducted preclinical research on the probiotic Lactobacillus rhamnosus GG (LGG) and determined that LGG improves epithelial crypt cell survival after radiation injury by protecting the entire small intestinal tract.

“If we offered LGG before radiation, then it was highly beneficial, but after radiation as a rescue or therapy once a patient had already developed diarrhea, then it was ineffective,” he reported. “This gave us a better idea of the timing, and that probiotics should be used as a prophylactic rather than a treatment strategy.”

The investigators then started a phase 1, open-label clinical trial to evaluate the prophylactic use of LGG on a well-defined population of patients with GI cancer receiving radiation therapy and 5-FU−based chemotherapy. The primary end point was safety and tolerability. The patients began LGG administration 3 days before the start of their radiation therapy and continued to take it twice daily during their active treatment and for 2 weeks posttreatment.

Probiotics Safe and Well-Tolerated

To date, 19 of 20 patients have been enrolled in the trial, and complete data are available for 10 patients. “The primary end points, in general, show that LGG was very well-tolerated and safe, and no adverse events have been reported,” Dr Ciorba said.

Diarrhea scores measured by Common Terminology Criteria for Adverse Events showed that patients treated with LGG had minimal toxicity compared with clinical controls and modern historical cohorts. Functional Assessment of Chronic Illness Therapy-Diarrhea subscale scores revealed that the majority of patients in the treatment group were satisfied with how they were coping with their illness, were not kept up at night by their diarrhea, and were not wearing protection for accidental stool soiling. “Across all of these various functional quality-of-life measures, patients seem to be doing quite well,” he reported.

According to Dr Ciorba, the microbiome is an important target in identifying intestinal radioprotectants, and LGG may have advantages over other microbes, because it has shown safety and effectiveness in humans and in animal models.

Based on these data, he and his co-investigators hope to prepare for a multicenter, phase 2b, randomized clinical trial. “Ultimately we’re going to be able to identify and test new specific bacterial products for safe and effective harnessing of the microbiome’s therapeutic potential,” he said. “So eventually we may not be getting a live probiotic bacteria but rather selecting a specific product from that probiotic as the therapy.”

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Last modified: February 2, 2017