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

Abstract

OBJECTIVES:

Report the feasibility, toxicities, and long-term results of a Phase I/II trial of 90Y-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, 90Y-cT84.66 anti-CEA at 16.6 mCi/m2 as an i.v. bolus infusion and on days 9-11 i.v. gemcitabine at 105 mg/m2 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/m2 and gemcitabine at 105 mg/m2 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.

• Authors: Benjamin Cahan, Lucille Leong, Lawrence Wagman, David Yamauchi, Stephen Shibata, Sharon Wilzcynski, Lawrence E Williams, Paul Yazaki, David Colcher, Paul Frankel, Anna Wu, Andrew Raubitschek, John Shively, Jeffrey Y C Wong
• Journal: Cancer biotherapy & radiopharmaceuticals (Cancer Biother Radiopharm) Vol. 32 Issue 7 Pg. 258-265 (Sep 2017) ISSN: 1557-8852 [Electronic] United States
• PMID: 28910150 (Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article)

Chemical References

• Antimetabolites, Antineoplastic
• Carcinoembryonic Antigen
• Floxuridine
• Deoxycytidine
• Gemcitabine

Topics

• Adult
• Aged
• Antimetabolites, Antineoplastic (therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Carcinoembryonic Antigen (therapeutic use)
• Colorectal Neoplasms (pathology)
• Deoxycytidine (analogs & derivatives, therapeutic use)
• Disease-Free Survival
• Female
• Floxuridine (therapeutic use)
• Humans
• Infusions, Intra-Arterial (methods)
• Liver (drug effects, pathology)
• Liver Neoplasms (drug therapy, radiotherapy)
• Male
• Maximum Tolerated Dose
• Middle Aged
• Radioimmunotherapy (methods)
• Gemcitabine