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Targeted Chemotherapy Shows Early Signs of Slowing Neuroblastoma Tumor Growth With Less Toxicity in Preclinical Models

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Key Points

  • The targeted method involves implanting a device directly into the center of the tumor. The device contains a chemotherapy-loaded silk sponge. The silk fabric binds to the chemotherapy agent, allowing the targeted release of the agent.
  • In a mouse model, researchers found that though the targeted delivery of doxorubicin was not more effective than intravenous delivery, the sustained release of vincristine on the silk sponge device slowed the rate of the tumor’s growth more effectively than delivering it intravenously.
  • Tumors usually reach 1,000 mm3 in about 10 days. With the sustained release of vincristine, it took 30 days for the tumor to reach the same size.

Surviving neuroblastoma as a child can come with just as many challenges as the cancer itself, mainly because of the toxic effects of chemotherapy. But a team of surgeons is in the nascent stages of developing a more targeted, less toxic method of treating neuroblastoma patients with chemotherapy. Their research results were presented at the 2015 Clinical Congress of the American College of Surgeons.

Normally, treatment of high-risk patients with neuroblastoma involves a surgical procedure to biopsy the tumor, followed by several rounds of chemotherapy, then another operation to resect the rest of the tumor, explained Bill Chiu, MD, FACS, Assistant Professor of Surgery at the University of Illinois at Chicago.

The current treatment protocol has achieved high 5-year survival rates, but the chemotherapy is associated with adverse effects. Some of the more serious late effects of chemotherapy for children include cardiomyopathy, neuropathy, infertility, growth problems, learning difficulties, or even secondary cancers.

Dr. Chiu and his team have begun developing a more targeted method to deliver the chemotherapy: “The ultimate goal is to create an alternative way to deliver chemotherapy to people with neuroblastoma so we can increase the dosage of chemotherapy but, at the same time, decrease the systemic toxicity,” he said.

New Method

The targeted method involves implanting a device directly into the center of the tumor. The device contains a chemotherapy-loaded silk sponge. The silk fabric binds to the chemotherapy agent, allowing the targeted release of the agent. The amount of silk used determines how much of the drug is released.

In a mouse model, Dr. Chiu and his team simulated neuroblastoma tumor growth in the mice’s adrenal glands. They then looked at how the tumors responded to two chemotherapy agents, vincristine and doxorubicin.

They compared delivery methods for the same dosages of each agent. One set of mice received vincristine delivered intravenously, while another set received it through the sustained release of the silk sponge implanted into the center of the tumor. With the sustained release, half of the chemotherapy agents were released immediately, and the remainder was released over the following 20 days.

Study Results

After measuring tumor growth through ultrasound, researchers found that though the targeted delivery of doxorubicin was not more effective than intravenous delivery, the sustained release of vincristine on the silk sponge device slowed the rate of the tumor’s growth more effectively than delivering it intravenously. Tumors usually reach 1,000 mm3 in about 10 days. With the sustained release of vincristine, it took 30 days for the tumor to reach the same size.

“This approach can complement the traditional systemic chemotherapy,” Dr. Chiu explained. “I don’t see this protocol replacing systemic chemotherapy altogether, but this method could be a helpful adjunct to the overall treatment plan.”

The next steps include more preclinical research to refine the delivery method, dosage, and chemotherapy drug combinations. “The way we deliver chemotherapy hasn’t changed much in the past 50 years. The cycles may change, the dose may vary, but we’re always giving it intravenously,” Dr. Chiu explained. “Giving it in a targeted way—such as going directly to the tumor and giving a lot of it—can decrease the systemic toxicity and hopefully prevent secondary malignancies.”

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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