Antibiotics in Cancer Treatment: Unraveling the Unseen Risks

Reading time: 3 minutes

Yonika Larasati

Since the advent of antibiotics more than one century ago, this class of drugs has tremendously changed humanity. In addition to treating bacteria-caused infectious diseases, antibiotics enable modern medical procedures, such as open-heart surgery and organ transplantation. Antibiotics are also essential for cancer patients. Cancer patients often face an increased risk of infection, as their immune systems have been weakened by both the disease and cancer chemotherapy. However, accumulating studies suggest that antibiotics should be used with caution in cancer patients receiving immunotherapy and chemotherapy.

Antibiotics are associated with worse outcomes in cancer patients receiving immunotherapy, a type of cancer treatment that helps our immune system kill cancer cells (1). Recent studies have demonstrated that antibiotic usage also negatively correlates with the outcomes of chemotherapies, a more conventional class of drugs that aim to eliminate cancer cells directly.

A study using a cancer patient registry in New South Wales, Australia, revealed that people having antibiotic exposure within 180 days before chemotherapy had poorer cancer survival (2). Intriguingly, the lowest patient survival was observed when the antibiotic was given close to the chemotherapy regimen (1-30 days before chemotherapy started). This effect was especially prominent for patients with lung and breast cancer.

Another recent study analyzed antibiotic administration during and after chemotherapy sessions in female patients with triple-negative breast cancer (TNBC), the most aggressive type of breast cancer (3). They found a negative association between the use of antibiotics and the survival of TNBC patients, regardless of the type of antibiotics used. Intriguingly, the more types of antibiotics taken, the worse the overall survival. 

While the correlation is clear, there is still much to learn to confirm the causality of antibiotics on the worse outcome of chemotherapy and immunotherapy. One of the possible mechanisms is that antibiotics create dysbiosis, an imbalanced state of microorganisms in the gut (gut microbiota) (4). Antibiotic-induced dysbiosis then affects cancer therapy’s efficacy – as accumulating studies using animal models reveal that gut microbiota is crucial for the efficacy and toxicity of cancer therapies (5). Oxaliplatin and cisplatin, the platinum-based compounds widely used as chemotherapy for solid tumors, show decreased anticancer efficacy in antibiotic-treated mice (6). Another example of drugs affected by gut microbiota is cyclophosphamide, a chemotherapy used for lymphoma, breast cancer, and ovarian cancer. The anticancer property of cyclophosphamide depends on the microbiota-regulated immune system, which is depleted in antibiotic-treated mice (7). More prospective studies using clinical data and animal models are crucial to establish the firm relationship between antibiotics, gut microbiota, and various cancer therapy outcomes. Using broad- vs. narrow-spectrum antibiotics might also help define the role of gut microbiota in the interaction between antibiotics and chemotherapy/immunotherapy.

More research is needed to determine which types of cancers are most affected by antibiotic usage. The survival of patients with lung and breast cancers is negatively impacted by antibiotic usage. The same trend is not observed for patients with colorectal, pancreatic, or prostate cancers (2). Is it due to different regimens of treatments used for different types of cancer? Or is it due to the intrinsic property of each cancer, as well as how the microbiota affects a specific type of cancer? More research is needed to answer these questions.

Overall, these studies highlight that careful considerations are needed to prescribe antibiotics for cancer patients, especially in the timing, number, and range of antibiotics. However, antibiotics are often also lifesaving for cancer patients with acute infections. Therefore, simply avoiding antibiotics for all cancer patients receiving chemotherapy would be impossible.  Healthcare providers must weigh the risks and benefits of giving antibiotics to cancer patients. Future studies discerning which types of antibiotics are ‘safe’ to be prescribed to cancer patients are needed.

Edited by Mallory Kane

Image source

Bibliography

1. Yang M, Wang Y, Yuan M, Tao M, Kong C, Li H, et al. Antibiotic administration shortly before or after immunotherapy initiation is correlated with poor prognosis in solid cancer patients: An up-to-date systematic review and meta-analysis. Int Immunopharmacol. 2020 Nov;88:106876.

2. Morrell S, Kohonen-Corish MRJ, Ward RL, Sorrell TC, Roder D, Currow DC. Antibiotic exposure within six months before systemic therapy was associated with lower cancer survival. J Clin Epidemiol. 2022 Jul;147:122–31.

3. Ransohoff JD, Ritter V, Purington N, Andrade K, Han S, Liu M, et al. Antimicrobial exposure is associated with decreased survival in triple-negative breast cancer. Nat Commun. 2023 Apr 12;14(1):2053.

4. Elvers KT, Wilson VJ, Hammond A, Duncan L, Huntley AL, Hay AD, et al. Antibiotic-induced changes in the human gut microbiota for the most commonly prescribed antibiotics in primary care in the UK: a systematic review. BMJ Open. 2020 Sep 21;10(9):e035677.

5. Fernandes MR, Aggarwal P, Costa RGF, Cole AM, Trinchieri G. Targeting the gut microbiota for cancer therapy. Nat Rev Cancer. 2022 Dec;22(12):703–22.

6. Iida N, Dzutsev A, Stewart CA, Smith L, Bouladoux N, Weingarten RA, et al. Commensal bacteria control cancer response to therapy by modulating the tumor microenvironment. Science. 2013 Nov 22;342(6161):967–70.

7. Viaud S, Saccheri F, Mignot G, Yamazaki T, Daillère R, Hannani D, et al. The intestinal microbiota modulates the anticancer immune effects of cyclophosphamide. Science. 2013 Nov 22;342(6161):971–6.