Outlining a Radioembolization/Chemotherapy Regimen for NET Liver Metastases

In an interview with CancerNetwork® at the 2025 North American Neuroendocrine Tumor Society (NANETS) Multidisciplinary NET Medical Symposium, Michael C. Soulen, MD, discussed the design of a phase 2 trial (NCT04339036) he conducted to ascertain the safety, feasibility, and efficacy of radioembolization with the radiosensitizing chemotherapy agents capecitabine (Xeloda) and temozolomide (Temodar) in patients with grade 2 or 3 liver-dominant neuroendocrine tumors (NETs).1,2

He began by highlighting the dosing schedule for chemotherapy, which was given in 4-week cycles, 2 weeks on and 2 weeks off, for as long as a patient could tolerate it. Additionally, Soulen identified a need to undertake a simulation procedure, wherein a harmless nuclear medicine agent is administered, to ensure that radioembolization can be done safety in conjunction with chemotherapy.

Furthermore, he explained that 7 days into the second cycle of chemotherapy, the radioembolization seeds are instilled, with the option to irradiate the other lobe the following month, if needed. Soulen concluded by saying that this combination regimen was hypothesized to attain a higher response rate and/or more durable responses vs either therapy alone.

Soulen is director of Interventional Oncology at the Abramson Cancer Center at the University of Pennsylvania.

Transcript:

We came up with this regimen where patients would start their [capecitabine-temozolomide]—which is an oral chemotherapy regimen taken for 2 weeks on, 2 weeks off—and you keep doing that every month for as long as it works, where the patient can tolerate it. They need to do that first to make sure they can tolerate the chemotherapy. [Because] a small number of patients [will not], if you are going to do radioembolization, you first must do a simulation procedure.

They need a catheterization, where we map out the plumbing of their liver. We do a test injection of a harmless nuclear medicine agent. We do a nuclear medicine SPECT scan. In the first month, they get their first cycle of chemotherapy––[we] make sure they can tolerate the chemotherapy, and they get the simulation for radioembolization––[and we] make sure that can be done safely. Then, the next month, on cycle 2, we drop the radioembolization procedure on day 7 of the 14 days of chemotherapy. They get a week of chemotherapy, they get their seeds instilled, and then on the next week of chemotherapy, the seeds are radiating their tumors. Then, if you need the other lobe treated, we do that the next month, and then they stay on the chemotherapy every month as long as it’s working and they can tolerate it.

The hope was that by combining the 2, that we would get either a higher response rate, more durable control, or both.

References

1. Soulen MC, Iyer R, Berman Z, Chauhan A, Thornton L. Multicenter phase 2 trial of Yttrium-90 radioembolization with capecitabine-temozolomide for grade 2 liver-dominant metastatic neuroendocrine tumors: interim report. Presented at the 2025 NANETS Multidisciplinary NET Medical Symposium; October 23-25, 2025; Austin, TX. Abstract 33445.
2. CapTemY90 for Grade 2/3 NET Liver Metastases (CapTemY90). ClinicalTrials.gov. Updated September 5, 2025. Accessed November 4, 2025. https://tinyurl.com/5euyvtu4