Integrated Capecitabine-Temozolomide with Radioembolization for Liver-Dominant G2 NETs: Long-Term Outcomes of a Single-Institution Retrospective Study.

PURPOSE: Capecitabine-Temozolomide (CapTem) is an oral chemotherapy regimen for NETs. Both drugs are radiosensitizers. Integrating CapTem and Y90 transarterial radioembolization (TARE) in patients with grade 2 neuroendocrine tumor (NET) liver metastases achieved an encouraging objective response rate (ORR) and progression-free survival (PFS) in a feasibility study. This study expands that report to a larger cohort with longer follow-up. METHODS: Therapy consisted of monthly cycles of capecitabine 600 mg/m2 twice daily for 14 days and temozolomide 150-200 mg/m2 on day 10-14. Simulation angiography was performed during the initial cycle. The dominant lobe was treated with 90Y-resin microspheres using BSA dosimetry on day 7 of the second cycle of CapTem. Patients with bilobar disease had the other lobe treated on day 7 of the third or fourth cycle. CapTem was continued until progression or intolerance. Clinical and laboratory assessment was done monthly and imaging every 3 months. RESULTS: 35/37 patients completed the prescribed regimen. Primary sites of disease were pancreas (16), lung (10), gut (7) and unknown (4). Mean duration of CapTem was 12 months (range, 4-32 months). ORR in the liver was 72% with a disease control rate of 100%. Median PFS was 36 months (95% CI, 25-45 months). Median overall survival was 41 months (95% CI, 24-87 months) from initiation of CapTemY90 therapy and 130 months (95% CI, 56-172 months) from initial diagnosis. CONCLUSION: Chemoradiation with CapTem and TARE provided durable control of G2 NET liver metastases for substantially longer than expectations for embolotherapy or chemotherapy alone.

Safety and Feasibility of Integrating Yttrium-90 Radioembolization With Capecitabine-Temozolomide for Grade 2 Liver-Dominant Metastatic Neuroendocrine Tumors.

OBJECTIVES: An integrated protocol combining capecitibine-temozolomide with yttrium-90 radioembolization (CapTemY90) for liver-dominant grade 2 neuroendocrine tumors (NETs) was designed in the hope of achieving synergistic improvement in liver disease control with no more than additive toxicities. This report describes the feasibility and safety of this regimen. METHODS: Twenty-one patients with unresectable grade 2 NET liver-dominant metastases without contraindications to radioembolization or to CapTem initiated therapy with capecitabine 600 mg/m twice daily for 14 days and temozolomide 150 to 200 mg/m in 2 divided doses on days 10 to 14, with 14 days between cycles. During the first cycle, simulation angiography was performed. The dominant lobe was radioembolized on day 7 of the second cycle. In patients with bilobar disease, the other lobe was treated on day 7 of the third or fourth cycle. RESULTS: Nineteen of 21 patients completed the protocol. Adverse events were as expected. Objective response rate was 74% in the liver and 55% for extrahepatic tumor. Median progression-free survival was not reached. Progression-free survival at 3 years was 67%, with 74% progression-free in the liver. CONCLUSIONS: CapTemY90 is feasible and safe for grade 2 NETs. Toxicities were additive. Oncologic outcomes suggest synergy.

Risk of liver abscess formation in patients with prior biliary intervention following yttrium-90 radioembolization.

PURPOSE: Patients without a competent sphincter of Oddi due to prior surgical or endoscopic therapy are at high risk for liver abscess following chemoembolization despite aggressive antimicrobial prophylaxis. We examined a cohort of such patients undergoing Y-90 resin radioembolization and compared them to a cohort of chemoembolized patients. METHODS: Review of our quality-assurance database identified 24 radioembolizations performed in 16 patients with prior biliary intervention. An aggressive prophylactic regimen of oral levofloxacin and metronidazole 2 days pre-procedure continuing for 14 days after, oral neomycin/erythromycin bowel prep the day before, and IV levofloxacin/metronidazole the day of treatment was prescribed. Patients underwent resin microsphere radioembolization dosed according to the BSA method. Patients had clinical, imaging, and laboratory assessment 1 month after each treatment, and then every 3 months. The chemoembolization cohort consisted of 13 patients with prior biliary intervention who had undergone 24 chemoembolization procedures. RESULTS: No radioembolization patient developed an abscess. In the cohort of chemoembolized patients who received the same prophylaxis, liver abscess occurred following 3 of 24 (12.5 %) procedures in 3 of 13 (23 %) patients, one fatal. CONCLUSIONS: This preliminary experience suggests that the risk of liver abscess among patients with prior biliary intervention may be lower following radioembolization than chemoembolization, which could potentially expand treatment options in this high-risk population.