Research Outcomes: Advancing Research to Improve Treatment

by St. Baldrick's Foundation
November 8, 2021

Your generosity makes a difference for kids with cancer. This edition of the St. Baldrick’s Foundation Research Outcomes recognizes research that is making treatments less toxic, evaluating new drugs, and working to prevent late effects. Thank you for making research possible.

Lab Equipment with text: Research Outcomes

FDA Orphan Drug Approval for Treating Osteosarcoma

New hope is on the horizon for osteosarcoma patients. Researchers including St. Baldrick’s funded Dr. Alex Huang tested Vactosertib, an adult pancreatic cancer drug, for its effect of preventing the growth and metastasis of osteosarcoma cells in models. These pre-clinical results provided foundation for its recent FDA Orphan Drug Designation approval. “The FDA Orphan Drug Designation approval opens a realistic path to testing Vactosertib in combination with other immune modulating therapies for the treatment of therapy-refractory sarcoma affecting the pediatric and adolescent and young adult population,” Dr. Huang said. The drug manufacturer MedPacto and Dr. Huang are now working to create a clinical trial for further testing.

Clinical Trial Provides Evidence to Reduce Toxic Treatments for Some Childhood ALL Patients

Since the 1970s standard treatment for childhood Acute Lymphoblastic Leukemia (ALL) has included adding chemotherapy (vincristine) and a steroid as pulse therapy (pulse therapy administers high doses of drugs at a time). Unfortunately, while standard, this treatment is also known to be associated with neuropsychological side effects, neuropathy and other late effects. Despite this, studies about the need for prolonged treatment with pulse therapy have been inconclusive, until now.

A clinical trial supported in part by St. Baldrick’s Foundation International Scholar Dr. Hui Zhang, published in Lancet Oncology established that this pulse therapy can be safely omitted in the second year of care in patients with low-risk disease without affecting their five-year event-free survival or overall survival.

Excluding vincristine plus steroid pulses should reduce many acute and late effects of treatment. This was the largest clinical trial ever conducted in childhood acute lymphoblastic leukemia. Next steps include confirming if this omission is also helpful for patients with intermediate or high-risk ALL.

New FDA Drug Approval to Address Drug Shortage for Childhood ALL

About 15% of children with ALL will develop an allergic reaction to the chemotherapy drug asparaginase. Asparaginase has long been an important part of treatment regimens in ALL. Erwinia asparaginase is an alternate form of the drug that can be substituted if a patient has an allergic reaction. However, manufacturing problems have led to global shortages of this alternative form.

Recent studies, including one by the Children’s Oncology Group, highlighted this problem and now there is hope that these shortages may be over. In June the FDA approved a new form of asparaginase, Rylaze, which has the same make up as Erwinia asparaginase but is manufactured in a more efficient way. Having the option to use Rylaze should reduce the drug shortages for patients.

Preventing and Treating Pediatric Radiation-Induced High-Grade Gliomas

Pediatric radiation-induced high-grade gliomas (RIGs) are a specific type of brain tumor caused by cranial radiation therapy for other cancers. As recently reported in Nature Communications, St. Baldrick’s Scholar Dr. Adam Green and colleagues found that the mutations that occur in these tumors are different than the mutations seen in primary gliomas (those that are not a result of cranial radiation). “It seems to be a different biological process that is driving these to develop” Dr. Green said.

Through further investigation the team discovered that patients with an impaired ability to repair DNA may be at higher risk for developing RIGs once they are exposed to radiation. If this weakness could be detected early, doctors could provide alternative treatments or monitor patients for RIGs more closely after radiation.

And it gets better. The researchers also tested a number of FDA-approved chemotherapy drugs and found that certain drugs seem to be effective against RIGs. Future plans involve further testing the drugs and eventually developing a clinical trial.

Protecting Kids’ Hearts from Long-term Side Effects of Cancer Treatments

Dr. Eric Chow received a St. Baldrick’s Consortium Research Grant to figure out if a readily available drug called “dexrazoxane,” when given at the same time as chemotherapy, can protect children’s hearts from the long-term side effects of their cancer treatments.

Many effective cancer treatments use chemotherapy agents that are known to damage the heart. Early heart disease has become the most common serious problem survivors of childhood cancers face besides recurrence of their original cancer or development of a new cancer. Because doctors do not yet know how effective dexrazoxane is and how safe it is to give in children receiving cancer treatment, its use has been limited.

“Thus far, our research has shown that over 500 children who previously received dexrazoxane as part of leukemia and lymphoma treatment from 1996-2001 do not appear more likely to die or have relapse of their cancer than 500 children who received the same cancer treatment, minus dexrazoxane, during the same time period,” Dr. Chow said. This work was recently published in Cancer.

Now that researchers know there are no adverse effects from the addition of this drug, next they will investigate how effective dexrazoxane has been in reducing heart disease among these children. Preliminary results suggest that the risk of more serious heart disease, including needing a heart transplant, may be lower in children who previously received dexrazoxane compared with children who did not.

Not every publication of research supported by St. Baldrick’s makes the news, but each one adds to the body of scientific knowledge that takes us one step closer to better outcomes for kids with cancer. Your continued support will make more research possible to Conquer Kids’ Cancer. 

Donate now and help support research into better treatments for kids with cancer.


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