Hepatic arterial infusion versus systemic therapy for hepatic metastases from colorectal cancer: A randomized trial of efficacy, quality of life, and molecular markers (CALGB 9481) Journal Article
| Authors: | Kemeny, N. E.; Niedzwiecki, D.; Hollis, D. R.; Lenz, H. J.; Warren, R. S.; Naughton, M. J.; Weeks, J. C.; Sigurdson, E. R.; Herndon, J. E. 2nd; Zhang, C.; Mayer, R. J. |
| Article Title: | Hepatic arterial infusion versus systemic therapy for hepatic metastases from colorectal cancer: A randomized trial of efficacy, quality of life, and molecular markers (CALGB 9481) |
| Abstract: | Purpose: Hepatic metastases derive most of their blood supply from the hepatic artery; therefore, for patients with hepatic metastases from colorectal cancer, hepatic arterial infusion (HAI) of chemotherapy may improve outcome. Methods: In a multi-institutional trial, 135 patients were randomly assigned to receive HAI versus systemic bolus fluorouracil and leucovorin. The primary end point was survival; secondary end points were response, recurrence, toxicity, quality of life, cost, and the influence of molecular markers. Results: Overall survival was significantly longer for HAI versus systemic treatment (median, 24.4 v 20 months; P = .0034), as were response rates (47% and 24%; P = .012) and time to hepatic progression (THP; 9.8 v 7.3 months; P = .034). Time to extrahepatic progression (7.7 v 14.8 months; P = .029) was significantly shorter in the HAI group. Quality-of-life measurements showed improved physical functioning in the HAI group at the 3- and 6-month follow-up assessments. Toxicity included grade ≥ 3 neutropenia (2% and 45%; P < .01), stomatitis (0% and 24%; P < .01), and bilirubin elevation (18.6% and 0; P < .01) in the HAI and systemic treatment groups, respectively. A greater proportion of men versus women receiving HAI experienced biliary toxicity (37% and 15%, respectively; P = .05). For HAI patients with thymidylate synthase levels in tumor less than or ≥ 4, the median survival was 24 and 14 months, respectively (P = .17). Conclusion: HAI therapy increased overall survival, response rate, THP, and was associated with better physical functioning compared with systemic therapy. Additional studies need to address the overall benefit and cost of new chemotherapy agents versus HAI alone or the combination of HAI with new agents. © 2006 by American Society of Clinical Oncology. |
| Keywords: | survival; adult; cancer survival; controlled study; human tissue; treatment outcome; treatment response; aged; middle aged; survival analysis; cancer surgery; major clinical study; clinical trial; disease course; neutropenia; cancer recurrence; fluorouracil; diarrhea; drug efficacy; drug withdrawal; side effect; liver neoplasms; follow up; antineoplastic agent; colorectal cancer; metastasis; quality of life; controlled clinical trial; multiple cycle treatment; randomized controlled trial; stomatitis; antineoplastic combined chemotherapy protocols; tumor markers, biological; combination chemotherapy; dexamethasone; pathology; protein p53; tumor marker; colorectal neoplasms; molecular marker; health care cost; liver metastasis; statistical significance; disease progression; multicenter study; colorectal tumor; folinic acid; liver tumor; intraarterial drug administration; infusions, intra-arterial; sex difference; hyperbilirubinemia; physical activity; thymidylate synthase; floxuridine; leucovorin; cost benefit analysis; hepatic artery; intravenous drug administration; injections, intravenous; biliary tract disease; levamisole |
| Journal Title: | Journal of Clinical Oncology |
| Volume: | 24 |
| Issue: | 9 |
| ISSN: | 0732-183X |
| Publisher: | American Society of Clinical Oncology |
| Date Published: | 2006-03-20 |
| Start Page: | 1395 |
| End Page: | 1403 |
| Language: | English |
| DOI: | 10.1200/jco.2005.03.8166 |
| PUBMED: | 16505413 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 124" - "Export Date: 4 June 2012" - "CODEN: JCOND" - "Source: Scopus" |
