Prospective phase II trial of combination hepatic artery infusion and systemic chemotherapy for unresectable colorectal liver metastases: Long term results and curative potential

Abstract

Background/objectives: Combination hepatic artery infusion (HAI) and systemic (SYS) chemotherapy for unresectable CRLM results in high tumor-response rates. This study represents an update of long-term survival and conversion to resectability in patients with unresectable CRLM treated with HAI and SYS chemotherapy in a phase II study.

Method: The primary endpoint was complete resection. Multivariate and landmark analysis assessed the effect of complete resection on progression-free (PFS) and overall survival (OS).

Results: From 2007 to 2012, 64 patients with median of 13 tumors were enrolled; 67% had prior chemotherapy. 33 patients (52%) were converted to resection. Median follow-up among survivors was 81 months. Median PFS and OS were 13 and 38 months, respectively, with 5-year-OS of 36%. Chemotherapy-naïve patients had 5-year-OS of 51%. Conversion to resection was the only independent factor prognostic of improved PFS and OS. Nine of 64 patients (14%) are NED (five since initial resection, three after resection of recurrent disease, one from chemotherapy alone) at median follow-up of 86 months from treatment initiation, and 72 months from last operative intervention.

Conclusion: Combination HAI and SYS is an effective therapy for high-volume unresectable CRLM, resulting in a high rate of resection, long-term survival, and the potential for cure.

Keywords: colorectal liver metastases; hepatectomy; hepatic artery infusion chemotherapy.

Figure 1

Waterfall plot demonstrating percentage decrease in tumor size in response to therapy. Dark bars represent patients previously treated with chemotherapy (n = 43); light bars represent patients without prior treatment (n = 21).

Figure 2

A. Overall survival of 64 patients treated with systemic chemotherapy and HAI FUDR, stratified by prior chemotherapy exposure. Median survival was 38 months for all patients (n=64) (95% CI: 28.8–53.7). The median survival for chemo-naïve patients (n=21) was 76.6 months (95% CI: 38.6-NR) and 29.7 months (95% CI: 21.5–40.2) for previously treated patients (n=43) (p=0.022). B. Progression-free survival of all patients stratified by prior chemotherapy exposure. Progression-free survival for all patients (n=64) was 13 months (95% CI: 9–16 months). Progression-free survival for chemotherapy-naïve patients was 19.7 months (95% CI: 13.1–23.4) and 10 months (95% CI: 6.2–14.3) for previously treated patients (p=0.020).

Figure 3

Landmark analysis of overall survival: 4 patients without 12 months followup were excluded. Time zero means 12 months from start of treatment. *HAI FUDR indicates hepatic artery infusional 5-fluoro-2-deoxyuridine.