What is PRRT?
PRRT is a molecular targeted therapy used to treat neuroendocrine tumors (NET). Molecular targeted therapies use drugs or other substances to identify and attack cancer cells while reducing harm to healthy tissue. PRRT delivers high doses of radiation to tumors in the body to destroy or slow their growth and reduce disease side effects.
The PRRT drug 177-Lu-Dotatate is approved by the U.S. Food and Drug Administration as a second-line treatment for certain patients with advanced NETs.
How does it work?
Patients who qualify for PRRT receive a dose of amino acid solution through an IV to protect the kidneys from radiation by reducing how much radiation they absorb. Then, octreotide, a synthetic cell-targeting protein, or peptide, is combined with a small amount of radioactive material, or radionuclide, to create a radiopeptide. When the radiopeptide is injected into a patient’s bloodstream, it binds to protein receptors called somatostatin receptors, located on NET cells, and delivers high doses of radiation to the tumor. Because it’s a systemic treatment, PRRT targets NETs with somatostatin receptors anywhere in the body.
The amino acid solution is also delivered to PRRT patients after they receive the radiopeptide injection. Because small amounts of radiation may remain in the body, patients are generally advised to take certain precautions after treatment, especially for the first one to two days.
Who may benefit from PRRT?
PRRT is recommended for patients who have somatostatin receptor-positive gastroenteropancreatic NETs, common neuroendocrine tumors that develop in the stomach, rectum, pancreas, and small and large intestine. Typically, NETs aren’t diagnosed until they’ve advanced, which means surgery may not be recommended because it may not remove all the patient’s tumors. Gastroenteropancreatic NETs that cannot be removed with surgery are typically treated with hormone therapy to control symptoms and tumor growth. But in cases when tumors continue to grow despite treatment, the PRRT drug 177-Lu-Dotatate, which combines the manufactured form of somatostatin with radioactive material, may be offered as a second-line treatment. In clinical trials, patients with tumors that were progressing despite first-line treatments and were given 177-Lu-Dotatate lived substantially longer, by almost three years, without cancer progression than patients who were treated with hormone therapy.
Not all gastroenteropancreatic NETs have somatostatin receptors, so PRRT is not an option for all NET patients. Imaging scans are used to determine whether the appropriate receptors are present.
What are the potential side effects?
The infusion of amino acids in PRRT helps decrease the amount of radiation the kidneys receive, but it may cause nausea and vomiting, which is typically managed with anti-nausea medication. In rare cases, patients may experience radiation toxicity to the liver and blood system, so patients who have already received heavy treatment to the liver may not be candidates for PRRT because of the toxicity risk. Regulating the dose of radiation may help.
What are the potential benefits to patients?
PRRT is generally delivered over the course of four, roughly four-hour-long infusions. The treatment is designed to slow the progression of disease in gastroenteropancreatic NET patients and to reduce the severity of disease side effects, such as diarrhea.
As a targeted therapy, PRRT offers patients more personalized, precise treatment, with medications tailored to the unique characteristics of each patient’s biology and the molecular properties of the tumor while limiting radiation exposure to healthy tissue.