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Published in: Targeted Oncology 4/2018

Open Access 01-08-2018 | Original Research Article

Low-Dose Continuous 5-Fluorouracil Combined with Leucovorin, nab-Paclitaxel, Oxaliplatin, and Bevacizumab for Patients with Advanced Pancreatic Cancer: A Retrospective Analysis

Authors: William H. Isacoff, Howard A. Reber, Rudolph Bedford, William Hoos, Lola Rahib, Alexander Upfill-Brown, Timothy Donahue, O. Joe Hines

Published in: Targeted Oncology | Issue 4/2018

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Abstract

Background

Continuous-infusion 5-fluorouracil (5FU) and calcium leucovorin plus nab-paclitaxel and oxaliplatin have been shown to be active in patients with pancreatic cancer. As a protracted low-dose infusion, 5FU is antiangiogenic, and has synergy with bevacizumab. As shown in the treatment of breast cancer, bevacizumab and nab-paclitaxel are also synergetic.

Objective

In this paper we retrospectively analyze the survival of 65 patients with advanced pancreatic cancer who were treated with low-dose continuous (metronomic) chemotherapy given in conjunction with conventional anti-VEGF therapy.

Patients and Methods

Since July of 2008, we have treated 65 patients with 5FU (180 mg/m2/day × 14 days) via an ambulatory pump. Calcium leucovorin (20 mg/m2 IV), nab-paclitaxel (60 mg/m2) IV as a 30-min infusion, and oxaliplatin (50 mg/m2) IV as a 60-min infusion were given on days 1, 8, and 15. Bevacizumab (5 mg/kg) IV over 30 min was administered on days 1 and 15. Cycles were repeated every 28–35 days. There were 42 women and 23 men, and the median age was 59 years. Forty-six patients had stage IV disease.

Results

The median survival was 19 months, with 82% of patients surviving 12 months or longer. The overall response rate was 49%. There were 28 patients who had received prior treatment, 15 of whom responded to therapy. Fifty-two patients had elevated CA 19-9 prior to treatment. Of these, 21 patients had 90% or greater reduction in CA 19-9 levels. This cohort had an objective response rate of 71% and a median survival of 27 months. Thirty patients stopped treatment due to disease progression, and an additional 22 stopped because of toxicity. One patient died while on therapy.

Conclusions

This non-gemcitabine-based regimen resulted in higher response rates and better survival than what is commonly observed with therapy given at conventional dosing schedules. Low-dose continuous (metronomic therapy) cytotoxic chemotherapy combined with antiangiogenic therapy is safe and effective.
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Metadata
Title
Low-Dose Continuous 5-Fluorouracil Combined with Leucovorin, nab-Paclitaxel, Oxaliplatin, and Bevacizumab for Patients with Advanced Pancreatic Cancer: A Retrospective Analysis
Authors
William H. Isacoff
Howard A. Reber
Rudolph Bedford
William Hoos
Lola Rahib
Alexander Upfill-Brown
Timothy Donahue
O. Joe Hines
Publication date
01-08-2018
Publisher
Springer International Publishing
Published in
Targeted Oncology / Issue 4/2018
Print ISSN: 1776-2596
Electronic ISSN: 1776-260X
DOI
https://doi.org/10.1007/s11523-018-0572-3

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