Phase I/II Trial of Anticarcinoembryonic Antigen Radioimmunotherapy, Gemcitabine, and Hepatic Arterial Infusion of Fluorodeoxyuridine Postresection of Liver Metastasis for Colorectal Carcinoma.

OBJECTIVES

Report the feasibility, toxicities, and long-term results of a Phase I/II trial of Y-labeled anticarcinoembryonic antigen (anti-CEA) (cT84.66) radioimmunotherapy (RIT), gemcitabine, and hepatic arterial infusion (HAI) of fluorodeoxyuridine (FUdR) after maximal hepatic resection of metastatic colorectal cancer to the liver.

METHODS

Patients with metastatic colorectal cancer to the liver postresection or ablation to minimum disease were eligible. Each cohort received HAI of FUdR for 14 days on a dose escalation schedule. The maximum HAI FUdR dose level planned was 0.2 mg/kg/day, which is the standard dose for HAI FUdR alone. On day 9, Y-cT84.66 anti-CEA at 16.6 mCi/m as an i.v. bolus infusion and on days 9-11 i.v. gemcitabine at 105 mg/m were given. Patients could receive up to three cycles every 6 weeks of protocol therapy. Four additional cycles of HAI FUdR were allowed after RIT.

RESULTS

Sixteen patients were treated on this study. A maximum tolerated dose of 0.20 mg/kg/day of HAI FUdR combined with RIT at 16.6 mCi/m and gemcitabine at 105 mg/m was achieved with only 1 patient experiencing grade 3 reversible toxicity (mucositis). After surgery, 10 patients had no evidence of visible disease and remained without evidence of disease after completion of protocol therapy. The remaining 6 patients demonstrated radiological visible disease after surgery and after protocol therapy 2 patients had a CR, 1 patient had PR, 2 had stable disease, and 1 had progression. With a median follow-up of 41.8 months (18.7-114.6), median progression free survival was 9.6 months. Two patients demonstrated long-term disease control out to 45+ and 113+ months.

CONCLUSION

This study demonstrates the safety, feasibility, and potential utility of HAI FUdR, RIT, and systemic gemcitabine. The trimodality approach does not have higher hematologic toxicities than seen in prior RIT-alone studies. Future efforts evaluating RIT in colorectal cancer should integrate RIT with systemic and regional therapies in the minimal tumor burden setting.