Novel models for prediction of benefit and toxicity with FOLFIRINOX treatment of pancreatic cancer using clinically available parameters

Despite modern chemotherapy regimens, survival of pancreatic cancer patients remains dismal. Toxicity is a major concern and it is a challenge to upfront identify patients with the highest benefit from aggressive polychemotherapy. We aimed to evaluate ORR and side effects of the FOLFIRINOX regimen,...

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Bibliographic Details
Published in:PloS one Vol. 13; no. 11; p. e0206688
Main Authors: Schlick, Konstantin, Magnes, Teresa, Ratzinger, Lukas, Jaud, Bernhard, Weiss, Lukas, Melchardt, Thomas, Greil, Richard, Egle, Alexander
Format: Journal Article
Language:English
Published: United States Public Library of Science 09.11.2018
Public Library of Science (PLoS)
Subjects:
Aged
Antineoplastic Agents - adverse effects
Antineoplastic Agents - therapeutic use
Bioindicators
Biology and Life Sciences
Body composition
Body composition (biology)
Body mass
Body mass index
Cancer
Cancer therapies
Chemotherapy
Drug Combinations
Female
Fluorouracil - adverse effects
Fluorouracil - therapeutic use
Follow-Up Studies
Hematology
Humans
Infectious diseases
Inflammation
Leucovorin - adverse effects
Leucovorin - therapeutic use
Male
Mathematical models
Medical diagnosis
Medical personnel
Medical research
Medicine and Health Sciences
Metastases
Metastasis
Middle Aged
Moths
Obesity
Oncology
Organometallic Compounds - adverse effects
Organometallic Compounds - therapeutic use
Pancreatic cancer
Pancreatic Neoplasms - diagnosis
Pancreatic Neoplasms - drug therapy
Pancreatic Neoplasms - mortality
Pancreatic Neoplasms - pathology
Parameters
Patients
Physicians
Prognosis
Research and Analysis Methods
Retrospective Studies
Rheumatology
Risk analysis
Risk factors
Side effects
Survival
Survival Analysis
Systematic review
Thrombocytosis
Toxicity
Tumor markers
Austria
ISSN:1932-6203, 1932-6203
Online Access:Get full text
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Summary:Despite modern chemotherapy regimens, survival of pancreatic cancer patients remains dismal. Toxicity is a major concern and it is a challenge to upfront identify patients with the highest benefit from aggressive polychemotherapy. We aimed to evaluate ORR and side effects of the FOLFIRINOX regimen, highlighting dose modification and to explore possible prognostic response factors as a clinical tool. This retrospective study includes 123 patients with metastatic PC that were treated with FOLFIRINOX between the years 2007 to 2016 in a single academic institution. Survival rates were analysed using the Kaplan-Meier method. Prognostic models including laboratory and clinical parameters were calculated using Cox proportional models in univariate and multivariate analyses. Median age at diagnosis was 64 years (47-78 years), 71 (57, 7%) were male and the majority had an ECOG performance status of 0 or 1 (63 patients; 83.7%). After a median follow up of 17.8 months, median progression free survival (PFS) and overall survival (OS) were 5.7 (4.55-6.84; 95%CI) and 11.8 months (9.35-14.24; 95%CI) respectively. Overall response rate with FOLFIRINOX was 34.9% and stable disease rate was 21.9%. Regarding Grade 3/4 side effects, 62 events, were reported in 37 patients. Looking at risk factors e.g. patient characteristics, tumor marker, inflammatory markers and body composition multivariate analyses proved CEA >4 elevation and BMI > 25 at the time point before palliative chemotherapy to be independent negative prognostic factors for OS. Grouping patients with no risk factor, one or two of these risk factors we analyzed a median OS of 17.4 moths, 9.6 months and 6.7 months (p<0.001) respectively. In addition we identified thrombocytosis and low BMI as predictors of early toxicity. This study identifies two easily available factors influencing overall survival with FOLFIRINOX therapy. By combining these two factors to create a score for OS, we propose a prognostic tool for physicians to identify patients, who are unlikely to benefit more from FOLFIRINOX or likely to experience toxicity.
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Competing Interests: The authors have declared that no competing interests exist.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0206688