May 31, 2019
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Ice chips a ‘no-cost intervention’ to improve oxaliplatin-induced oral symptoms

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Kim Reiss Binder, MD
Kim Reiss Binder

An oral cryotherapy intervention that involved ice chips appeared to reduce oxaliplatin-induced oral symptoms among a cohort of patients with gastrointestinal cancer, according to study findings.

“Our study highlights a low-tech, no-cost intervention that has the potential to improve quality of life for patients undergoing treatment with oxaliplatin-based therapy,” Kim Reiss Binder, MD, assistant professor of medicine in the department of medicine at University of Pennsylvania, and a HemOnc Today Next Gen Innovator, said in a press release. “Patients being treated with chemotherapy often have reduced appetites and may have trouble finding foods or beverages that appeal to them. Not being able to tolerate anything cold can further limit their ability to eat and drink, which certainly lowers quality of life.”

Chemotherapy-induced oral thermal hyperalgesia is a common toxicity associated with oxaliplatin-based therapy. Reiss Binder and colleagues sought to assess the efficacy of oral cryotherapy, which involves patients keeping ice chips in their mouths during oxaliplatin-based chemotherapy infusions, in preventing oral thermal hyperalgesia.  

The single-institution, randomized, controlled trial included patients at Abramson Cancer Center at the University of Pennsylvania scheduled to receive standard oxaliplatin treatment for a gastrointestinal malignancy. Patients (n = 50) were randomly assigned 1:1 to an oral cryotherapy group or a control group.

Results showed a significantly lower rate of oral symptoms after the first treatment cycle among patients in the intervention group (32%) vs. those in the control group (72%). Researchers also observed a smaller magnitude of difference in symptom scores before vs. after the first treatment cycle among those in the intervention group vs. the control group (P = .001). Moreover, the duration of ice chip exposure appeared associated with improvements in oral symptoms over time (P = .02). 

“Our findings suggest that it might make sense to educate patients about this strategy during standard chemotherapy teaching,” Reiss Binder said in the release.

HemOnc Today spoke with Reiss Binder about the study, what she and colleagues found and what subsequent research should entail.

Question: What prompted this research?

Answer: In the treatment of gastrointestinal cancers, we often use the chemotherapy drug oxaliplatin, which, among other things, causes cold sensitivity in the mouth. When a person eats or drinks anything cold, he or she experiences strange sensations in the mouth and throat. Some describe it as tingling or shards of glass; others feel like their throat is closing. A number of studies have looked at reducing the blood flow to specific areas of the body to reduce toxicity in an area experiencing a side effect from treatment. One involved the cold cap, which resulted in a reduction in chemotherapy-induced hair loss. Other research has shown that when patients had one hand in a cold glove during chemotherapy infusion, there was a substantial reduction in peripheral neuropathy compared with the ungloved hand. Thus, we accepted that by potentially reducing blood flow to a part of the body, we could potentially limit the toxicity at the skin and subcutaneous level. By extension, we thought that if we had patients cool down their mouth while undergoing an oxaliplatin-based infusion, potentially we could limit oral toxicity.      

Q: How did you conduct the study?

A: We enrolled patients who were to undergo oxaliplatin therapy for a gastrointestinal malignancy for at least 2 months. We randomly assigned patients to two groups. In the first group, patients were asked to keep ice chips in their mouth for as long as they could tolerate while undergoing treatment. Patients in the second group were asked not eat or drink anything below room temperature while undergoing chemotherapy infusion. We asked patients to do this during every treatment cycle for as long as they could. Every patient completed questionnaires before and throughout treatment to assess oral and peripheral symptoms and tell us how these symptoms affected their quality of life.  

Q: What did you find?

A: We found that during the first courses of chemotherapy, patients in the intervention group had a significant reduction in oral symptoms compared with controls. Those who were able to tolerate the ice chips in their mouths longer had the biggest benefit. Our effect seemed to dwindle later in therapy, and we lost the significant difference between groups. However, we had far fewer patients on therapy later in the study, so our power to detect a difference between groups diminished. 

Q: Did any of your findings surprise you?

A: We were surprised to find that patients in the intervention group reported significantly fewer peripheral neuropathy symptoms. There is certainly the possibility of a placebo effect. However, a recent study showed that healthy patients who consumed an ice slurry for a few minutes had a significant reduction in rectal temperature, suggesting that cooling the back of the throat can lower core body temperature. It could be hypothesized that persistently keeping ice in one’s mouth might lower core temperature and cause peripheral vasoconstriction, leading to less exposure of the peripheral nerves to oxaliplatin. This is only a hypothesis and has not been specifically tested.

Q: What should subsequent research entail?

A: Our study was small, and additional research would need to be done to confirm our findings. However, vasoconstriction during chemotherapy infusion to limit specific toxicities might be one of the ways we can help patients feel better while on treatment. – by Jennifer Southall

References:

Bauman B, et al. J Natl Compr Canc Netw. 2019;doi:10.6004/jnccn.2018.7110.

Hanai A, et al. J Natl Cancer Inst. 2017;doi:10.1093/jnci/djx178.

Nanjia J, et al. JAMA. 2019;doi:10.1001/jama.2016.20939.

Onitsuka S, et al. Sci Rep. 2018;doi:10.1038/s41598-018-21086-6.

For more information:

Kim Reiss Binder, MD, can be reached at Perelman Center for Advanced Medicine,
3400 Civic Center Blvd., Philadelphia, PA 19104; email: kim.reissbinder@uphs.upenn.edu.

Disclosure: Reiss Binder reports no relevant financial disclosures.