Scientists Uncover Potentially Serious Side Effect of Common Cancer Drug

by Tatsuya Nakamura
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Hyperglycemia in Breast Cancer

Scientists have recently unveiled a potentially significant adverse effect associated with a commonly used cancer medication. Recent research has brought to light a notable occurrence of hyperglycemia in breast cancer patients undergoing treatment with the drug alpelisib. This study underscores the critical importance of early detection and effective management of elevated blood sugar levels, aiming to enhance the efficacy of cancer therapies while minimizing the risk of severe side effects.

The research inquiry delved into the prevalence of hyperglycemia induced by alpelisib, examining its contributing factors and outlining strategies for its treatment in individuals grappling with metastatic breast cancer.

Recent investigations have unveiled a concerning trend among breast cancer patients who are administered the oral medication alpelisib. They are experiencing a heightened incidence of hyperglycemia, a condition characterized by elevated blood sugar levels. This discovery was meticulously documented in a recent publication in the peer-reviewed journal “Cancer,” a publication affiliated with the American Cancer Society.

Alpelisib, as a drug, is designed to specifically inhibit the activity of the phosphoinositide 3-kinase (PI3K) protein, a pivotal player in cell growth regulation. Mutations within this protein have been implicated in the development of cancer. In 2019, the United States Food and Drug Administration granted approval for the use of alpelisib in combination with fulvestrant, a medication that impedes estrogen receptors, for the treatment of specific forms of metastatic breast cancer characterized by mutations in the gene responsible for encoding a PI3K subunit.

Side Effects and Research Findings

Regrettably, the targeting of PI3K by alpelisib can lead to hyperglycemia as a side effect, which, if severe, can result in complications such as dehydration or kidney damage, necessitating hospitalization. Dr. Sherry Shen and her colleagues from the Memorial Sloan Kettering Cancer Center embarked on a mission to elucidate the incidence, risk factors, and patterns of treatment associated with alpelisib-induced hyperglycemia in patients with metastatic breast cancer, either enrolled in a clinical trial or receiving standard care at their institution.

Among the 147 patients who received alpelisib as part of their standard care regimen, the incidence of hyperglycemia was alarmingly high at 80.3%, with 40.2% experiencing severe hyperglycemia. In contrast, among the 100 patients participating in a clinical trial, the rates were relatively lower, at 34.0% for any grade of hyperglycemia and 13.0% for severe hyperglycemia. The median time for the onset of hyperglycemia following the initiation of alpelisib treatment was approximately 16 days. Notably, individuals with initially elevated hemoglobin A1c levels, an indicator of high blood sugar often seen in prediabetes or diabetes, were at a heightened risk of developing hyperglycemia.

Among patients who did develop hyperglycemia, approximately 66.4% received treatment, with the diabetes drug metformin being the most commonly administered therapy.

Managing Hyperglycemia and Future Directions

Dr. Shen emphasized the importance of proactively addressing the glycemic status of patients with PI3KCA mutations who may be eligible for alpelisib treatment. She stressed the need to monitor hemoglobin A1c levels and collaborate with the patient’s primary care physician or endocrinologist to optimize blood sugar control. This proactive approach should be initiated several months before commencing alpelisib treatment, as hyperglycemia typically manifests within the first two weeks of therapy. By taking preemptive measures to improve glycemic health and manage prediabetes or diabetes, there is hope that the risk of developing hyperglycemia can be reduced, thereby minimizing the likelihood of discontinuing a potentially effective cancer medication.

Senior author Dr. Neil M. Iyengar noted that optimizing blood sugar levels often entails modifying dietary and exercise habits and potentially introducing specific medications. He also mentioned ongoing clinical trials aimed at assessing whether metabolic interventions such as the ketogenic diet or newer diabetes medications could enhance the efficacy of cancer therapies targeting the PI3K pathway.

Reference: Shen, S., Chen, Y., Carpio, A., Chang, C., & Iyengar, N. M. (2023). Incidence, risk factors, and management of alpelisib-associated hyperglycemia in metastatic breast cancer. “Cancer,” DOI: 10.1002/cncr.34928. Published on September 25, 2023.

Frequently Asked Questions (FAQs) about Hyperglycemia in Breast Cancer

What is the main focus of the research mentioned in the text?

The primary focus of the research is to investigate the occurrence and management of hyperglycemia in breast cancer patients undergoing treatment with the drug alpelisib.

What is alpelisib, and why is it relevant to breast cancer treatment?

Alpelisib is a medication designed to inhibit the phosphoinositide 3-kinase (PI3K) protein, which plays a crucial role in cell growth. It is relevant to breast cancer treatment because it is used in combination with fulvestrant to treat specific types of metastatic breast cancer characterized by mutations in the gene responsible for encoding a PI3K subunit.

What are the side effects of alpelisib, and why are they a concern?

One of the side effects of alpelisib is hyperglycemia, which is characterized by elevated blood sugar levels. This side effect is concerning because severe hyperglycemia can lead to complications such as dehydration, kidney damage, and hospitalization.

What were the key findings of the research regarding hyperglycemia and alpelisib treatment?

The research found that hyperglycemia occurred in a significant percentage of patients receiving alpelisib, with a higher incidence in those receiving it as standard care. Additionally, an initially elevated hemoglobin A1c level was identified as a risk factor for developing hyperglycemia.

How can hyperglycemia in breast cancer patients receiving alpelisib be managed?

Managing hyperglycemia in these patients involves proactive monitoring of blood sugar levels, collaboration with primary care physicians or endocrinologists, and potential treatment with medications such as metformin. Lifestyle modifications, including dietary and exercise changes, may also be recommended.

Are there ongoing efforts to improve the treatment of hyperglycemia in alpelisib-treated patients?

Yes, ongoing clinical trials are exploring various metabolic interventions, including dietary approaches like the ketogenic diet and newer diabetes medications, to enhance the efficacy of cancer therapies targeting the PI3K pathway and improve glycemic control in these patients.

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