Phase II Trial of Hepatic Artery Infusional and Systemic Chemotherapy for Patients With Unresectable Hepatic Metastases From Colorectal Cancer

Abstract

Purpose Evaluate conversion rate of patients with unresectable colorectal-liver metastasis to complete resection with hepatic-arterial infusion plus systemic chemotherapy including bevacizumab. Patients and Methods Forty-nine patients with unresectable CRLM were included in a single-institution phase II trial. Conversion to resection was the primary outcome. Secondary outcomes included overall (OS), progression-free survival (PFS), and response rates (RR). Multivariate and Landmark analyses were performed to evaluate survival differences between resected and non-resected patients. Results Median number of tumors was 14 and 65% were previously treated patients. A high biliary toxicity rate was found in the first 24 patients whose treatment included Bev. The remaining 25 patients were treated without Bev. Overall RR was 76% (4 complete responses). Twenty-three patients (47%) achieved conversion to resection at a median of 6 months from treatment initiation. Median OS and PFS for all patients was 38 (95% CI: 28–not reached) and 13 months (95% CI: 7–16). Bev administration did not impact outcome. Conversion was the only factor associated with prolonged OS and PFS in multivariate analysis. On landmark analysis, resected patients had longer OS compared to those who did not undergo resection (3-year OS: 80% vs. 26%). Currently 10 of 49 (20%) patients are NED at a median follow up of 39 months (32–65). Conclusion In patients with extensive unresectable CRLM, the majority of whom were previously treated, 47 % were able to undergo complete resection after combined HAI and systemic therapy. Conversion to resection is associated with prolonged survival.

Transarterial chemoembolization (TACE) for colorectal liver metastases—current status and critical review

“…In one randomized study, a significant survival benefit is reported for patients undergoing continuous HAI with 5-fluoro-deoxy-uridine (FUDR) compared with the control arm (5-fluoro-uracil (5FU)/BMT) (13.5 versus 7.5 months; p=0.03)) [28]. Recent results of a non-controlled trial promote HAI in combination with systemic chemotherapy including bevacizumab [29]. The overall response rate was 76 % (inclusive of 4 complete responses), and 23 patients (47 %) achieved conversion to resection at a median of 6 months from initial treatment.…”

“…Patients who had undergone resection had a better overall survival than those who did not (3-year overall survival of 80 versus 26 %). Ten of 49 (20 %) of the patients with surgical resection had no evidence of disease at a median follow-up of 39 months (32-65 months) [29]. Procedure-related specific complications of HAI such as hepatic artery dissection and thrombosis, portcatheter occlusion as well as pump failure and infection are reported in up to 21, 5, 2, and 3 %, respectively [30].…”

Hepatic Arterial Infusion for Unresectable Liver Metastases from Colorectal Cancer: The Dawn of a New Era?

“…3 Although the patient population and interventions are similar, the two studies have some notable differences. D'Angelica and colleagues at MSKCC performed a prospective, phase 2 clinical trial for HAI combined with systemic therapy, using conversion to resectability as the primary outcome.…”

Treatment Options in Colorectal Liver Metastases: Hepatic Arterial Infusion

“…In patients who were chemotherapynaïve, the median survival was 50.8 months, and for patients who were previously treated the median survival was 35 months. D'Angelica et al [53] evaluated 49 patients with unresectable liver metastases from CRC treated with HAI plus systemic chemotherapy in a prospective study. The overall response rate was 76%, 47% of patients were converted to resection at 6 months after treatment start, and median overall survival for all patients was 38 months.…”