A Systematic Review of Clinical Response and Survival Outcomes of Downsizing Systemic Chemotherapy and Rescue Liver Surgery in Patients with Initially Unresectable Colorectal Liver Metastases

14565 Background: Although locoregional treatments such as hepatic arterial infusion (HAI) claim the advantage of delivering higher doses of anticancer agents directly into the affected organ, there is substantial lack of evidence for benefit in terms of overall survival (OS). To test the hypothesis that systemic chemotherapy affects OS of patients with unresectable colorectal liver metastases treated with HAI. Furthermore, we investigated patient- and tumor-related predictive factors that might identify patients who most benefit from HAI regimen. Methods: In this retrospective study, 153 consecutive patients treated at our institution were considered. In group-A (n=72), patients were treated with HAI alone (floxuridine (FUDR) 0.2 mg/Kg + leucovorin (LV) 4 mg/m2 + desamethasone 20 mg 14 days/month) between 1994 and 1999. In group-B (n=81), patients were treated with the same HAI regimen combined with systemic chemotherapy (5-fluorouracil (5FU) 450 mg/m2 + LV 20 mg/m2) between 1999 and 2003. Results: No difference in OS was observed between group-A and group-B (median OS: 18.0 and 19.1 months, respectively). Considering all patients (group A + group B), low tumor load was associated with a better tumor response rate, but none of the traditional clinico-pathological prognostic factors correlated with OS. Median OS was better in patients with less than 50% of liver parenchyma involvement (21.3 vs 13.2 months; P<0.0001) as well as in responders (complete or partial response) versus non-responders (24.4 vs 13.4 months; P<0.0001). The combination of low tumor load with good tumor response to HAI was the only variable retained at multivariate analysis, and identified a subgroup of patients with a very favorable clinical outcome (median survival: 34.2 months; hazard ratio: 0.347, CI: 0.249–0.564, P< 0.0001). Conclusions: Combination with 5FU+LV systemic chemotherapy did not lead to an OS benefit over FUDR-based HAI alone. The identification of tumor response predictors is urgently needed, as it would lead to the tailored treatment of patients with low load but unresectable metastatic liver disease who most benefit from HAI therapy. No significant financial relationships to disclose.

Download Full-text

A single-arm, phase II study of intrahepatic chemotherapy in patients with unresectable colorectal liver metastases.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.4_suppl.162 ◽

2020 ◽

Vol 38 (4_suppl) ◽

pp. 162-162

Author(s):

Kate Elenna Besel ◽

Yoo-Joung Ko ◽

Paul Jack Karanicolas ◽

Christina Yiyoung Kim

Keyword(s):

Liver Metastases ◽

Colorectal Liver Metastases ◽

Systemic Chemotherapy ◽

Infusion Pump ◽

Disease Free Survival ◽

The United States ◽

Median Number ◽

Time To Progression ◽

Unresectable Colorectal Liver Metastases ◽

Number Of Cycles

162 Background: In Canada, the standard of care for patients with unresectable colorectal liver metastases (uCRLM) is systemic chemotherapy and/or best supportive care. Intrahepatic chemotherapy using floxuridine (FUDR), in addition to systemic chemotherapy, is available in the United States but its adoption outside major centers has been limited. Methods: A single-center, prospective study of intrahepatic chemotherapy for the treatment of patients with uCRLM was initiated at Sunnybrook Health Sciences Centre in 2014. Patients underwent implantation of a hepatic infusion pump with resection of their primary tumor (if in place). Patients were treated with FUDR in addition to systemic chemotherapy (FOLFIRI or FOLFOX). Study objectives include the rate of conversion to complete resection, time to progression (TTP), disease-free survival (DFS), time to progression in liver, overall survival (OS), andresponse rate (RR). Results: From 2014 to present, 46 patients have been enrolled. Median age at the time of HAIP placement was 51 years (30-72 years). Males accounted for 61% (28/46). All patients received at least one cycle of systemic chemotherapy prior to surgery. 44 patients received a minimum of one cycle of FUDR, with the median number of cycles of FUDR received being 7.5 (0-28 cycles). Only one patient was unable to receive any FUDR after surgery. Response rate was 80% (n = 37/46). Three patients are too early for assessment. Eight (17.4%) patients have undergone liver resection. Median number of cycles of FUDR prior to resection was 7 (4-13 cycles). TTP, DFS, time to progression in liver, OS, and safety will be presented. Conclusions: The addition of intrahepatic chemotherapy to best systemic therapy may provide an increase in the rate of conversion to complete hepatic resection in patients with uCRLM. Clinical trial information: ON1233.

Download Full-text