Selective internal radiation therapy (SIRT) for liver metastases with concomitant systemic oxaliplatin, 5-fluorouracil and folinic acid: A phase I/II dose escalation study

Abstract

3657 Background: SIR-Spheres (Sirtex Medical Limited, Sydney, Australia) contain the pure β-emitter, yttrium-90, used to selectively irradiate liver metastases from colorectal cancer. The combination of SIRT with systemic 5-fluorouracil (5-FU) and folinic acid (LV) has been shown to improve survival when compared to systemic chemotherapy alone (Van Hazel et al JSO 2004;88:78). The administration of oxaliplatin in combination with 5-FU/LV improves response rates and it is a radiosensitiser. The goal of this study was to evaluate the safety and efficacy of combining oxaliplatin and 5-FU/LV chemotherapy with SIRT Methods: Seventeen patients with liver metastases from colorectal cancer, who had not received previous chemotherapy for metastatic disease, were entered into the study. Chemotherapy consisted of the FOLFOX4 regimen, modified with an oxaliplatin dose escalated from 30 mg/m2 to 85 mg/m2 in order to assess safety and tolerability. SIR-Spheres were implanted by injection into the hepatic arterial system on days 3 or 4 of the first chemotherapy cycle. Results: Most patients experienced nausea or abdominal pain within 48 hours of SIRT. Mild peripheral neuropathy was evident in 6 of the first 11 patients, appearing between cycles 10–12. Grade 3/4 transient neutropenia was seen in 5 of 11 patients. Three NCI Grade 3 events were documented in 2 of 3 patients at the 30 mg/m2 tier (diarrhea, nausea/vomiting, fever). Six grade 3 events were seen in 4 of 8 patients in the 60 mg/m2 tier (diarrhea, nausea/vomiting, abdominal pain, fever, leukopenia, anaemia). Only one grade 3 event has been exhibited to date in 1 of 6 patients in the 85 mg/m2 tier (nausea/vomiting). Partial responses (RECIST) were seen in all of the first 11 patients. Median time to liver progression is currently 11+ months. Conclusions: The administration of SIRT in combination with oxaliplatin appears to possess an acceptable toxicity profile. The maximum tolerated dose has not been defined, but it is expected to be at least 85 mg/m2. We plan to proceed to phase III trials of chemoradiation using FOLFOX4 with or without SIRT. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Sirtex