Prospective randomized study comparing hepatic intra-arterial injection of Yttrium-90 resin-microspheres (HAI-Y90) with protracted IV 5FU (5FU CI) versus 5FU CI alone for patients with liver-limited metastatic colorectal cancer (LMCRC) refractory to standard chemotherapy (CT)

Abstract

4096 Background: Chemorefractory LMCRC has a poor prognosis. We hypothesized a significant improvement of the patient's outcome after internal radiotherapy of the hepatic metastases with HAI-Y90 given along with 5FU CI over 5FU CI alone. Methods: This prospective, multicentric, randomized trial compared arm A: 5FU CI (300 mg/m2 D1–14 q3weeks) with arm B: HAI-Y90 and 5FU CI (225 mg/m2 D1–14 followed by 300 mg/m2 D1–14 q3weeks) until disease progression. Eligibility criteria were: chemo-refractory (5FU, oxaliplatin, irinotecan) LMCRC, PS max 2, normal direct bilirubin, and no lung shunting. Primary endpoint was time to liver progression (TTLP). Secondary endpoints were time to progression (TTP), overall survival (OS) and safety. Cross-over (HAI-Y90 monotherapy) was permitted in arm A after disease progression. Analysis was by intention to treat. To detect an increase in median TTLP from 6 to 18 weeks, 35 local progressions were needed (alpha 5%, power 90%). Distribution of time to events variables was modelled through Cox regression (likelihood ratio tests). Results: Trial randomized 46 patients (pts) of whom 44 were eligible for analysis (23 in arm A and 21 in arm B). Pts’ characteristics in the 2 arms were well balanced. Local progression was documented in 41 pts. Median length of follow-up was 108 weeks. Results are summarized in the table . Treatment was well tolerated with few side effects reported, essentially grade 3 asthenia (5 pts; 22%) in arm A. Most pts (25/44) received further treatment after local progression, including 10 pts with cross-over to HAI-Y90 in arm A, which may explain to some degree the lack of difference in OS. Conclusions: HAI-Y90 with 5FU CI significantly improves TTLP and TTP over 5FU CI alone and is a valid salvage therapeutic option for chemo-refractory LMCRC. [Table: see text] No significant financial relationships to disclose.