Continuous hepatic arterial infusion of 5-fluorouracil for unresectable colorectal liver metastases: Phase II study**

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.

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Phase I/II study of irinotecan, UFT, and leucovorin with hepatic arterial infusion in colorectal cancer patients with unresectable liver metastases: Preliminary results

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.14549 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 14549-14549

Author(s):

T. Yamaguchi ◽

H. Matsumoto ◽

K. Takahashi ◽

M. Yasutome ◽

T. Mori

Keyword(s):

Colorectal Cancer ◽

Phase I ◽

Liver Metastases ◽

Phase Ii ◽

Phase I Study ◽

Phase Ii Study ◽

Hepatic Arterial Infusion ◽

Arterial Infusion ◽

Unresectable Liver Metastases ◽

Colorectal Cancer Patients

14549 Background: To determine the maximum-tolerated dose (MTD) and to evaluate the efficacy and tolerability of combination chemotherapy of irinotecan (CPT-11), UFT and leucovorin (LV) with hepatic arterial infusion (HAI) in colorectal cancer patients with unresectable liver metastases. Methods: Patients who had unresectable liver metastases from colorectal cancer were treated concurrently with intravenous CPT-11 on day1 of each 14-day treatment cycle with dose escalation, with orally UFT and LV on day 1–7 of each cycle, and with HAI of 5-FU on day 8–14 of each cycle. The primary objective of this phase I study was to determine the MTD of biweekly intravenous CPT-11 and UFT/LV with HAI of 5-FU. In the phase II study, the primary endpoint was to determine the response rate. Results: In the phase I study, the recommended dose of CPT-11 for phase II study was 140 mg/m2 combined with UFT 300 mg/m2/day, LV 75 mg/body/day and 5-FU 2,000 mg/body/week. Sixteen patients were enrolled onto the phase II study. The six patients treated at the recommended dose during the phase I study also included in the phase II analysis (n = 22). Median number of liver metastases was 12 (range, 3 to 35). Median size of maximum diameter was 6.3 cm (range, 2.0 to 12.0 cm). The most common adverse event was neutropenia. The complete and partial response rate totaled 81.8%. Median survival time has not been reached yet. Eleven patients (50.0%) were ultimately able to undergo liver resection. Conclusions: The combination chemotherapy of CPT-11 and UFT/LV with HAI was safe, well tolerate and effective in current population of the patients with unresectable liver metastases from colorectal cancer. Updated toxicity and response data will be available in the spring of 2007. No significant financial relationships to disclose.

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