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When children with certain types of cancer are treated with a drug called methotrexate, they’re typically also given significant IV fluids to clear the chemotherapy from the body and get them feeling better faster. The problem is that the fluids have their own set of side effects.

A group of researchers from VCU Massey Comprehensive Cancer Center and the Children’s Hospital of Richmond at VCU (CHoR)—led by pediatric clinical pharmacy specialist Cady Noda, PharmD—studied whether providers could safely give less fluid without impacting the management of the chemo side effects. Their paper was recently published in Pediatric Blood & Cancer.

“This study was the first investigator-initiated trial on pediatric cancer patients at VCU and CHoR. It was a small study but it suggests that Cady’s hypothesis was correct, and it could make getting methotrexate a better and safer experience for children in the future,” said Matt Schefft, DO, associate chief quality and safety officer for CHoR and one of the study’s co-authors. “She presented this work at a national hematology and oncology conference and drew a lot of interest. This is one of many examples of her commitment to continuous quality improvement in pediatric care.”

Additional study co-authors include Lindsey Gwaltney, R.N., clinical research operations manager at Massey; Megan Lo, M.D., nephrologist at CHoR; and Roy Sabo, Ph.D., member of the Developmental Therapeutics research program at Massey.

Noda explained the impetus, process and results of her study on methotrexate and IV fluids.

What prompted you to do this study on methotrexate and IV fluids?

Our main goal with this study was to improve the supportive care of children with acute lymphoblastic leukemia who receive high-dose methotrexate. We know that the treatment can be tough on kids, and one of the biggest challenges is helping them clear the medication from their bodies safely. We wanted to find a way to give methotrexate that would allow kids to feel better faster, so they can get back home and enjoy being kids again. By exploring the role of things like IV fluids, we hope to decrease medication side effects and help kids spend less time in the hospital.

When is methotrexate prescribed for children?

High-dose methotrexate is commonly prescribed for children diagnosed with leukemia, lymphoma, central nervous system tumors and osteosarcoma. Our study specifically focused on children receiving methotrexate as part of their chemotherapy treatment for acute lymphoblastic leukemia (ALL). This treatment requires the child to be admitted to the hospital, where methotrexate is administered over 24 hours. Afterward, they receive post-hydration IV fluids. The child’s labs are closely monitored, and they must remain in the hospital to receive IV fluids until the methotrexate is cleared from their system.

What are the benefits of IV fluids in conjunction with methotrexate?

Nephrotoxicity—rapid decline in kidney function caused by medication—is an important potential consequence of methotrexate therapy. Acute nephrotoxicity can contribute to acute and chronic renal impairment complicating future therapy, as well as treatment delays related to delayed methotrexate clearance. IV fluids are commonly given alongside methotrexate to help protect the kidneys. Proper hydration is important in reducing the risk of side effects and ensuring the medication works as intended. However, like anything, too much hydration can have its own risks, and there is limited research on exactly how much hydration is necessary to prevent side effects of methotrexate.

What are the side effects of the increased fluids?

While proper hydration is important, too much fluid can also pose risks. Excessive hydration can lead to complications such as increased strain on the kidneys, delayed clearance of methotrexate from the body, and worsened side effects like mucositis, anemia and low blood cell counts. Delayed clearance of methotrexate also causes the child to remain in the hospital longer, which may decrease quality of life.

Were the results of the study what you expected?

Our findings suggest that reduced post-hydration may be safe and still allow for a similar time to methotrexate elimination, which is a promising development. Our supportive care practices at Massey and CHoR are being optimized based on this study's results. In light of the ongoing national IV fluid shortage, this study also offers an alternative approach to safely administer methotrexate to children with ALL, potentially preventing delays in their chemotherapy treatments.

A future multi-center study is needed to further confirm the benefits of reduced hydration in optimizing supportive care for pediatric patients receiving methotrexate.

How do studies like this lead to improved quality and safety when caring for kids?

Studies like this are essential because they allow us to identify potential risks and benefits in real-world treatment scenarios. By understanding how various interventions work, we can make more informed decisions that prioritize the well-being of children. This research helps guide clinical practices, ensuring that treatments are as safe, effective and comfortable as possible.

I am grateful to the families and patients who participated in this study! I’m also thankful to be part of an institution that truly prioritizes research aimed at improving care for our pediatric patients.

This was repurposed from an article originally published by the Children’s Hospital of Richmond at VCU.

Written by: Kate Marino