Document Type
Journal Article
Publication Title
BMC Cancer
Volume
20
Issue
1
PubMed ID
32641104
Publisher
Springer
School
School of Medical and Health Sciences
RAS ID
35210
Funders
Eli Lilly and Company
Abstract
© 2020 The Author(s).
Background:
Pancreatic cancer has a poor prognosis and few choices of therapy. For patients with adequate performance status, FOLFIRINOX or gemcitabine plus nab-paclitaxel are preferred first-line treatment. 5-Fluorouracil (5-FU)-based therapy (e.g. FOLFIRI, OFF, or FOLFOX) are often used in patients who previously received gemcitabine-based regimens. A systematic review was conducted of the safety and efficacy of FOLFOX for metastatic pancreatic cancer following prior gemcitabine-based therapy. A Bayesian fixed-effect meta-analysis with adjustment of patient performance status (PS) was conducted to evaluate overall survival (OS) and compare outcomes with nanoliposomal irinotecan combination therapy.
Methods:
PubMed.gov, FDA.gov, ClinicalTrials.gov, congress abstracts, Cochrane.org library, and EMBASE database searches were conducted to identify randomized controlled trials of advanced/metastatic disease, prior gemcitabine-based therapy, and second-line treatment with 5-FU and oxaliplatin. The database search dates were January 1, 1990-June 30, 2019. Endpoints were OS and severe treatment-related adverse events (TRAEs). Trial-level PS scores were standardized by converting Karnofsky grade scores to Eastern Cooperative Oncology Group (ECOG) Grade, and overall study-weighted PS was calculated based on weighted average of all patients. Results: Of 282 studies identified, 11 randomized controlled trials (N = 454) were included in the meta-analysis. Baseline weighted PS scores predicted OS in 10 of the 11 studies, and calculated PS scores of 1.0 were associated with a median OS of 6.3 months (95% posterior interval, 5.4-7.4). After adjusting for baseline PS, FOLFOX had a similar treatment effect profile (median OS, range 2.6-6.7 months) as 5-FU/leucovorin plus nanoliposomal irinotecan therapy (median OS, 6.1 months; 95% confidence interval 4.8-8.9). Neutropenia and fatigue were the most commonly reported Grade 3-4 TRAEs associated with FOLFOX.
Conclusions:
Baseline PS is a strong prognostic factor when interpreting the efficacy of 5-FU and oxaliplatin-based therapy of pancreatic cancer after progression on first-line gemcitabine-based regimens. When baseline PS is considered, FOLFOX has a similar treatment effect as 5-FU and nanoliposomal irinotecan therapy and a comparable safety profile. These findings suggest that 5-FU and oxaliplatin-based therapies remain an acceptable and alternative second-line treatment option for patients with pancreatic cancer and adequate PS (e.g. ECOG 0-1) following gemcitabine treatment.
DOI
10.1186/s12885-020-07110-x
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Comments
Wainberg, Z. A., Feeney, K., Lee, M. A., Muñoz, A., Gracián, A. C., Lonardi, S., ... & Hecht, J. R. (2020). Meta-analysis examining overall survival in patients with pancreatic cancer treated with second-line 5-fluorouracil and oxaliplatin-based therapy after failing first-line gemcitabine-containing therapy: Effect of performance status and comparison with other regimens. BMC Cancer, 20, Article 633.
https://doi.org/10.1186/s12885-020-07110-x