An exploratory study of body composition as a predictor of dose-limiting toxicity in metastatic pancreatic cancer treated with gemcitabine plus nab-paclitaxel.
Aged
Albumins
/ administration & dosage
Antineoplastic Combined Chemotherapy Protocols
/ administration & dosage
Body Composition
/ drug effects
Body Mass Index
Body Surface Area
Canada
Deoxycytidine
/ administration & dosage
Dose-Response Relationship, Drug
Female
Humans
Lumbar Vertebrae
/ diagnostic imaging
Male
Maximum Tolerated Dose
Middle Aged
Muscle, Skeletal
/ diagnostic imaging
Paclitaxel
/ administration & dosage
Pancreatic Neoplasms
/ drug therapy
Peripheral Nervous System Diseases
/ chemically induced
Predictive Value of Tests
Reference Values
Retrospective Studies
Tomography, X-Ray Computed
/ methods
Gemcitabine
Body composition
Chemotherapy
Pancreatic cancer
Sarcopenia
Toxicity
Journal
Clinical nutrition (Edinburgh, Scotland)
ISSN: 1532-1983
Titre abrégé: Clin Nutr
Pays: England
ID NLM: 8309603
Informations de publication
Date de publication:
08 2021
08 2021
Historique:
received:
19
02
2021
revised:
29
05
2021
accepted:
24
06
2021
pubmed:
7
8
2021
medline:
28
12
2021
entrez:
6
8
2021
Statut:
ppublish
Résumé
Body composition is increasingly being studied as a method of predicting chemotherapy toxicity. Our study aimed to evaluate associations of body composition with treatment toxicity in a group of pancreatic cancer patients treated with gemcitabine plus nab-paclitaxel. A retrospective review was performed for all patients who received first-line gemcitabine plus nab-paclitaxel for metastatic pancreatic cancer at a northern Alberta cancer institute (Canada) from 2014 to 2017. Total lean body mass (LBM) was derived from measurements of muscle surface area at L3 on baseline computed tomography (CT) scans. Optimal stratification, or minimal p-value analysis, was used to assess for a threshold of nab-paclitaxel dose per LBM (mg/kg) associated with a higher risk of dose-limiting toxicity (DLT). 152 patients were included in the study, of whom 62 (40.8%) experienced DLT. nab-Paclitaxel dose/LBM ranged from 0.98 to 8.76 mg/kg. A threshold for nab-paclitaxel dose/LBM that optimally predicted risk of DLT was identified at 5.83 mg/kg. Above this cut-off, 18/31 (58.1%) patients experienced DLT, compared to 44/121 (36.4%) patients below (p = 0.028). Patients above this cut-off had a higher incidence of peripheral neuropathy compared to those below, though this was not statistically significant based on an adjusted p-value threshold (48.4 vs. 29.8% respectively, p = 0.050). Body mass index, body surface area, and absolute initial doses of nab-paclitaxel or gemcitabine did not significantly impact likelihood of DLT. nab-Paclitaxel dose normalized to LBM, based on CT-derived measures of skeletal muscle, has potential to predict risk of chemotherapy toxicity. Chemotherapy dosing based on body composition, rather than conventional anthropometric measures, may be effective in reducing treatment toxicity.
Sections du résumé
BACKGROUND
Body composition is increasingly being studied as a method of predicting chemotherapy toxicity. Our study aimed to evaluate associations of body composition with treatment toxicity in a group of pancreatic cancer patients treated with gemcitabine plus nab-paclitaxel.
METHODS
A retrospective review was performed for all patients who received first-line gemcitabine plus nab-paclitaxel for metastatic pancreatic cancer at a northern Alberta cancer institute (Canada) from 2014 to 2017. Total lean body mass (LBM) was derived from measurements of muscle surface area at L3 on baseline computed tomography (CT) scans. Optimal stratification, or minimal p-value analysis, was used to assess for a threshold of nab-paclitaxel dose per LBM (mg/kg) associated with a higher risk of dose-limiting toxicity (DLT).
RESULTS
152 patients were included in the study, of whom 62 (40.8%) experienced DLT. nab-Paclitaxel dose/LBM ranged from 0.98 to 8.76 mg/kg. A threshold for nab-paclitaxel dose/LBM that optimally predicted risk of DLT was identified at 5.83 mg/kg. Above this cut-off, 18/31 (58.1%) patients experienced DLT, compared to 44/121 (36.4%) patients below (p = 0.028). Patients above this cut-off had a higher incidence of peripheral neuropathy compared to those below, though this was not statistically significant based on an adjusted p-value threshold (48.4 vs. 29.8% respectively, p = 0.050). Body mass index, body surface area, and absolute initial doses of nab-paclitaxel or gemcitabine did not significantly impact likelihood of DLT.
CONCLUSIONS
nab-Paclitaxel dose normalized to LBM, based on CT-derived measures of skeletal muscle, has potential to predict risk of chemotherapy toxicity. Chemotherapy dosing based on body composition, rather than conventional anthropometric measures, may be effective in reducing treatment toxicity.
Identifiants
pubmed: 34358833
pii: S0261-5614(21)00322-8
doi: 10.1016/j.clnu.2021.06.026
pii:
doi:
Substances chimiques
130-nm albumin-bound paclitaxel
0
Albumins
0
Deoxycytidine
0W860991D6
Paclitaxel
P88XT4IS4D
Gemcitabine
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4888-4892Informations de copyright
Copyright © 2021 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.
Déclaration de conflit d'intérêts
Conflict of interest None declared.