Alternating Hepatic Arterial Infusion and Systemic Chemotherapy for Liver Metastases From Colorectal Cancer: A Phase II Trial Using Intermittent Percutaneous Hepatic Arterial Access

• Published in: Journal of clinical oncology Vol. 19; no. 9; pp. 2404 - 2412
• Main Authors: COPUR, M. Sitki, CAPADANO, Mary, LYNCH, James, GOERTZEN, Timothy, MCCOWAN, Timothy, BRAND, Randall, TEMPERO, Margaret
• Format: Journal Article
• Language: English
• Published: Baltimore, MD American Society of Clinical Oncology 01.05.2001; Lippincott Williams & Wilkins
• Subjects: Adult; Aged; Antimetabolites, Antineoplastic - administration & dosage; Antineoplastic agents; Biological and medical sciences; Chemotherapy; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - mortality; Female; Fluorouracil - administration & dosage; Fluorouracil - adverse effects; Hepatic Artery; Humans; Infusions, Intra-Arterial; Leucovorin - administration & dosage; Leucovorin - adverse effects; Liver Neoplasms - drug therapy; Liver Neoplasms - mortality; Liver Neoplasms - secondary; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Survival Rate; Adenocarcinoma; Antineoplastic agent; Rectal disease; Prognosis; Intravenous administration; Liver; Hepatic disease; Administration schedule; Calcium folinate; Metastasis; Floxuridine; Percutaneous route; Intermittent; Phase II trial; Intestinal disease; Intraarterial administration; Colon; Fluorouracil; Hepatic artery; Human; Drug combination; Enzyme; Transferases; Fluoropyrimidine derivatives; Enzyme inhibitor; Malignant tumor; Thymidylate synthase; Colonic disease; Chemotherapy; Treatment; Methyltransferases; Antimetabolic; Rectum; Digestive diseases; Pyrimidine derivatives
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2001.19.9.2404

To evaluate the objective response to a short course of hepatic arterial infusion (HAI) using temporary, percutaneously placed catheters alternating with systemic prolonged continuous infusion fluorouracil (ci 5-FU) and daily oral leucovorin (L). Eligible patients were previously untreated (except for adjuvant therapy) adults with liver-predominant metastases, with Eastern Cooperative Oncology Group performance status of 0 to 2. Treatment regimen included HAI with fluorodeoxyuridine (FUDR) 60 mg/m2/d and L 15 mg/m2/d continuously infused daily for 4 days. After a 1-week rest, ci 5-FU was administered through a central venous access device using a dose of 180 mg/m2/d with a fixed dose of oral L at 5 mg/m2/d for 21 out of 28 days. Cycles were repeated every 6 weeks. After four cycles of therapy, patients were maintained on ci 5-FU and daily oral L until evidence of progression. Forty-three patients were enrolled onto this trial. One patient was ineligible. The objective response rate for all patients (17 partial, zero complete) was 41% (95% confidence interval [CI], 26% to 56%). Five patients were not able to receive at least one complete cycle of HAI. Among patients who received at least one complete cycle of HAI, the response rate was 46% (95% CI, 30% to 62%). Five patients underwent a liver resection after enrolling onto the protocol. At the time of analysis, estimated median time to progression was 6 months, and estimated median overall survival was 13 months. The objective response rate was comparable to that achieved with more prolonged and more frequent HAI using FUDR. This approach should be studied as an acceptable alternative to surgically placed hepatic arterial catheters/pumps and may have a role as neoadjuvant therapy for liver metastases that are unresectable, as well as an adjuvant role for patients with resected hepatic metastatic colorectal cancer.