Phase I trial of adjuvant hepatic arterial infusion (HAI) with floxuridine (FUDR) and dexamethasone plus systemic oxaliplatin, 5-fluorouracil and leucovorin in patients with resected liver metastases from colorectal cancer Journal Article
| Authors: | Kemeny, N.; Capanu, M.; D'Angelica, M.; Jarnagin, W.; Haviland, D.; DeMatteo, R.; Fong, Y. |
| Article Title: | Phase I trial of adjuvant hepatic arterial infusion (HAI) with floxuridine (FUDR) and dexamethasone plus systemic oxaliplatin, 5-fluorouracil and leucovorin in patients with resected liver metastases from colorectal cancer |
| Abstract: | Background: The purpose of the study was to determine the maximum tolerated dose of systemic oxaliplatin (oxal), 5-fluorouracil (5-FU) and leucovorin (LV) that could be administered with hepatic arterial infusion (HAI) of floxuridine (FUDR) and dexamethasone (Dex) in the adjuvant setting after hepatic resection. Methods: Thirty-five patients with resected liver metastases were entered into a phase I trial using HAI FUDR/Dex with escalating doses of oxal and 5-FU. Results: The initial dose of HAI FUDR was fixed at 0.12 mg/kg × pump volume divided by pump flow rate plus Dex infused over the first 2 weeks of a 5-week cycle. Systemic chemotherapy was delivered on days 15 and 29 with the doses of oxal escalated from 85 to 100 mg/m<sup>2</sup> and the 5-FU 48-h continuous infusion doses from 1000 to 2000 mg/m<sup>2</sup>. The LV dose was fixed at 400 mg/m<sup>2</sup>. Dose-limiting toxic effects were diarrhea, 8.5%, and elevated bilirubin, 8.5%. With a median follow-up of 43 months, the 4-year survival and progression-free survival were 88% and 50%, respectively. Conclusions: Adjuvant therapy after liver resection with HAI FUDR/Dex plus systemic oxal at 85 mg/m<sup>2</sup> and 5-FU by continuous infusion at 2000 g/m<sup>2</sup> with LV at 400 mg/m<sup>2</sup> is feasible and appears effective. Randomized studies comparing this regimen to systemic FOLFOX are suggested. © The Author 2009. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. |
| Keywords: | adult; cancer survival; clinical article; controlled study; treatment outcome; aged; disease-free survival; middle aged; survival rate; clinical trial; neutropenia; fluorouracil; diarrhea; drug dose reduction; drug efficacy; drug safety; side effect; liver neoplasms; adjuvant therapy; cancer adjuvant therapy; chemotherapy, adjuvant; colorectal cancer; adenocarcinoma; progression free survival; controlled clinical trial; liver toxicity; multiple cycle treatment; cohort studies; thrombocytopenia; antineoplastic combined chemotherapy protocols; dexamethasone; continuous infusion; abdominal pain; drug dose escalation; febrile neutropenia; colorectal neoplasms; liver metastasis; folinic acid; heparin; infusions, intra-arterial; nausea and vomiting; liver resection; alkaline phosphatase blood level; maximum tolerated dose; phase 1 clinical trial; drug dose increase; oxaliplatin; floxuridine; organoplatinum compounds; leucovorin; bilirubin blood level; drug tolerance; hepatic artery; adjuvant hai fudr; oxaliplatin/fu/lv; flow rate; ulcer; vitamin b complex |
| Journal Title: | Annals of Oncology |
| Volume: | 20 |
| Issue: | 7 |
| ISSN: | 0923-7534 |
| Publisher: | Oxford University Press |
| Date Published: | 2009-07-01 |
| Start Page: | 1236 |
| End Page: | 1241 |
| Language: | English |
| DOI: | 10.1093/annonc/mdn769 |
| PUBMED: | 19233901 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 11" - "Export Date: 30 November 2010" - "CODEN: ANONE" - "Source: Scopus" |
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