Biomarkers may predict gastrointestinal symptoms during chemotherapy
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Two blood-based biomarkers may help identify patients with cancer who are more likely to experience gastrointestinal symptoms during chemotherapy.
Levels of omega-3 and interleukin-8 appeared associated with development of chemotherapy-associated GI symptoms among women with breast cancer, according to results of a study led by researchers at University of California, Irvine.
Researchers conducted a secondary analysis of a prospective cohort study.
Investigators measured baseline levels of a panel of biomarkers among 31 women with stage I to stage III breast cancer. They also evaluated GI symptoms at chemotherapy initiation and at least 6 weeks into treatment.
Women with higher concentrations of both biomarkers appeared more likely to experience appetite loss during chemotherapy. Women with higher concentrations of interleukin-8 experienced worsened nausea and vomiting.
“Gastrointestinal symptoms are quite prevalent among [patients with breast cancer] and survivors, especially those who are undergoing chemotherapy,” Alexandre Chan, PharmD, MPH, founding chair of UC Irvine School of Pharmacy and Pharmaceutical Sciences’ department of clinical pharmacy practice, told Healio. “We have antiemetics and drugs that can potentially manage these symptoms, but many patients are still suffering from unresolved gastrointestinal symptoms. This may be because there are still underlying mechanisms that we don’t understand, and inflammation may play a role.”
Healio spoke with Chan and study co-author Daniela Arcos, clinical research coordinator in the UC Irvine’s School of Pharmacy and Pharmaceutical Sciences, about the findings — some of which were unexpected — and how they may be used to reduce chemotherapy-associated GI symptoms.
Healio: Why did conduct this study?
Arcos: We already had some data from a previous study conducted in Singapore, and we were interested in further exploring the relationship between biomarkers — specifically related to omega-3 and inflammation — and GI symptom progression among patients with breast cancer undergoing chemotherapy. The idea of this secondary analysis was to be able to leverage these data to learn a bit more about these relationships.
Healio: How did you conduct this study?
Chan: This was a prospective, observational study. We followed patients with breast cancer from the time of diagnosis to at least 6 weeks into treatment, while they were undergoing chemotherapy. We collected data about their symptoms through questionnaires on quality of life. We also collected blood samples at different time points before treatment and during chemotherapy to see how these biomarkers changed over time.
Healio: What did you find?
Arcos: Higher levels of docosahexaenoic acid (DHA) — which is an omega-3 fatty acid — and interleukin-8, which is an inflammatory cytokine, at baseline predicted greater appetite loss 6 weeks after chemotherapy initiation among patients with breast cancer. Higher levels of interleukin-8 predicted worse nausea and vomiting.
Healio: Do you have any potential explanation for these findings?
Chan: Most patients with cancer are already in an inflammatory state. Because of that — plus undergoing cytotoxic chemotherapy — patients ended up having even more inflammation in the GI tract, which is very sensitive. Most of the time, cells are rapidly dividing and turning over, and that is where cytotoxic drugs and chemotherapy drugs will be attacking. That would release even more inflammation and more inflammatory markers. So, that explains some of the phenomena we are observing. Being able to pinpoint what inflammatory markers are there may help us identify targets or even develop treatments that potentially can target that specific cytokine.
We were expecting there would be a change in symptoms based on omega-3 levels, but we didn’t know what direction that change would take. We thought there might be a decrease, but instead we observed that symptoms increased/worsened over time. A lot more research needs to be done to understand these variations.
Healio: What might this finding mean as far as recommending or discouraging use of omega-3 supplements?
Chan: Our original premise, based on the idea that omega-3s would decrease symptoms in these samples, was to try to figure out whether supplementing with omega-3s might help with some GI symptoms. Surprisingly, though, we saw an increase.
We do know that some of these omega-3 fish oil supplements can cause GI symptoms, as well, so I don’t think the data are definitive enough to make recommendations in terms of omega-3 supplementation.
Arcos: In our study, we considered omega-3 levels from plasma. Hopefully, in future studies, we would be able to consider more accurate levels of omega-3 through whole blood and through cell membranes.
Healio: What are the potential implications of this study?
Chan: A lot of research in the supportive care arena is looking at interventions that can reduce inflammation among our patients to relieve some of these side effects. This research isn’t limited to GI symptoms. We’re looking at cancer-related fatigue and cognitive impairment, as well. Even other modalities, like integrative oncology, might be able to use this information to develop interventions for reducing some of these symptoms. The information we got from our study is useful as another potential pathway we can target for reducing GI symptoms.
Arcos: It is very interesting that we did find a predictive value. The fact that baseline levels of these biomarkers predicted progression of symptoms up to 6 weeks later is very useful. It will be interesting to see if that finding is replicated on a larger scale. If we are able to lower inflammation before starting treatment, this could have positive implications for these chemotherapy-associated symptoms later on.
Healio: Is there anything else you feel is important to emphasize?
Arcos: We are working on a study proposal that aims to further explore the associations between omega-3 supplementation and how — paired with additional dietary guidance — this could lower inflammation, as well as prevent GI symptoms. It’s an exciting area, and we are hoping to learn more about it in the future.
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For more information:
Daniela Arcos can be reached at darcos1@hs.uci.edu.
Alexandre Chan, PharmD, MPH, can be reached at a.chan@uci.edu.
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