Vitamin D Deficiency in Breast Cancer Patients Increases Risk of Chemo-Induced Neuropathy

According to the findings of the primary univariate analysis, 20.7% of patients with vitamin D deficiency experienced grade 3 or higher sensory CIPN compared to 14.2% of patients with sufficient vitamin D levels (OR, 1.57; 95% CI, 1.14-2.15; P=.005). The investigators noted that the link remained after correcting for age and chemotherapy treatment schedule (adjusted OR [aOR], 1.65; 95% CI, 1.18-2.30; P =.003). After correcting for self-reported race, however, significance was lost (aOR, 1.39; 95% CI, 0.98-1.97; P =.066). Patients who self-reported as Black (OR, 2.48; 95% CI, 1.57-3.86; P =.001), those of other races (OR, 1.84; 95% CI, 1.06-3.07; P =.025), and those randomized to receive paclitaxel twice weekly (OR, 2.37; 95% CI, 1.73-3.29; P =.001) had more CIPN events.

“These results suggest that vitamin D supplementation in patients with lower levels of vitamin D may reduce peripheral neuropathy, and particularly high-grade peripheral neuropathy, which would improve these patients’ long-term quality of life,” senior researcher Daniel L. Hertz, Pharm.D., Ph.D., University of Michigan College of Pharmacy, said in a press release on the analysis findings (2). “There are barely any negative consequences that come from taking steps to increase vitamin D levels. Patients can easily take safe, inexpensive, and widely available over-the-counter supplements.”

The researchers evaluated data from the randomized phase 3 SWOG S0221 trial, which looked at several chemotherapy dose schedules in 2849 eligible patients with early-stage breast cancer. Of that population, 1620 had at least two serum samples available, and 1191 patients were chosen for biomarker analysis.

Racial Disparity in Vitamin D Levels

Age, BMI, and race were all taken into account while calculating the results. Researchers discovered that vitamin D insufficiency was more common in Black patients (77.1%) than in White patients (28.2%; OR, 8.56; 95% CI, 5.44-13.92; P.001), as was CIPN incidence (29.4% vs 14.3%, respectively; OR, 2.48; 95% CI, 1.57-3.86; P.001).

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When researchers examined mechanical hypersensitivity in mice based on vitamin D deficiency, they discovered that a vitamin D-deficient diet resulted in neurotoxicity-like symptoms.

Prevalence of Chemotherapy-Induced Peripheral Neuropathy in Breast Cancer Patients

Up to 70% of people who undergo paclitaxel treatment develop CIPN. Despite this, no documented medications exist to prevent or treat CIPN, or to ease its sensory or motor symptoms. Vitamin D pretreatment is the first proven and theoretically modifiable biomarker that may minimize the risk of CIPN from paclitaxel.

The analysis had significant limitations, according to the researchers. To begin, while there was evidence that vitamin D deficiency was more prevalent in Black patients, researchers admitted that the study had a small number of non-White individuals. Larger populations are required to further understand the relationship between race, vitamin D, and CIPN. Further research could come from the phase 2 EAZ171 trial (NCT04001829), which will look for ways to minimize CIPN after docetaxel or paclitaxel in African-American patients with stage I to III breast cancer.

Furthermore, because data was obtained from another trial and S0221 did not include patients who experienced grade 2 CIPN or documented thorough paclitaxel dose details, CIPN grades could have been misclassified.

Second, even though Common Terminology Criteria for Adverse Events (CTCAE) is considered less sensitive for detecting subjective toxicities, researchers chose CTCAE data as the primary CIPN endpoint rather than patient-reported outcomes (PROs) because CTCAE was available in all patients in the study. Furthermore, no data on other CIPN risk factors, such as preexisting peripheral neuropathy or the presence of diabetes, were collected. As a result, more research is needed to understand whether adequate vitamin D levels prevent CIPN and enhance treatment outcomes in individuals with breast and other cancer types.

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References:

  1. Vitamin D insufficiency as a risk factor for paclitaxel-induced peripheral neuropathy in SWOG

    Chen CS, Zirpoli G, Barlow WE, et al. Vitamin D insufficiency as a risk factor for paclitaxel-induced peripheral neuropathy in SWOG S0221.2023;21(11):1172-1180. doi:10.6004/jnccn.2023.7062
  2. New research in JNCCN suggests a simple and inexpensive option for reducing a major chemotherapy side-effect

    New research in JNCCN suggests a simple and inexpensive option for reducing a major chemotherapy side effect. News release. National Comprehensive Cancer Network.November 7, 2023. Accessed November 8, 2023. https:bit.ly/49stLS0

Source: Medindia

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