The Influence of Body Composition on the Systemic Exposure of Paclitaxel in Esophageal Cancer Patients

Doorn, Leni van; Crombag, Marie-Rose B S; Rier, Hánah N.; Vugt, Jeroen L.A. van; Kesteren, Charlotte van; Bins, Sander; Mathijssen, Ron H.J.; Levin, Mark‐David; Koolen, Stijn L.W.

doi:10.3390/ph14010047

Cited by 5 publications

(2 citation statements)

References 26 publications

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“… 29 In addition, according to a pharmacokinetic study, in 184 oesophageal cancer patients treated with paclitaxel, skeletal muscle measures were not superior to BSA in predicting pharmacokinetics of paclitaxel and did not have any added value to BSA. 30 …”

Section: Discussionmentioning

confidence: 99%

The association between skeletal muscle measures and chemotherapy‐induced toxicity in non‐small cell lung cancer patients

Jong

Chargi

Herder

et al. 2022

J cachexia sarcopenia muscle

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Background Chemotherapy‐induced toxicities frequently occur in non‐small cell lung cancer (NSCLC) patients treated with platinum‐based chemotherapy. Low skeletal muscle mass (SMM) has been associated with a higher incidence of toxicities for several types of cancers and cytostatics. The aim of this study was to evaluate the association between skeletal muscle measures and chemotherapy‐induced toxicity in a large cohort of NSCLC patients. Methods A multicentre prospective follow‐up study (PGxLUNG, NTR number NL5373610015) in NSCLC patients was conducted. Included were patients diagnosed with NSCLC (stage II–IV) treated with first‐line platinum‐based (cisplatin or carboplatin) chemotherapy of whom pretreatment imaging was available. Skeletal muscle area (SMA) segmentation was performed on abdominal imaging at the level of the third lumbar vertebra (L3). SMA at the level of L3 was corrected for squared height (m2) to yield the lumbar skeletal muscle mass index (LSMI). Skeletal muscle density (SMD) was calculated as the mean Hounsfield Unit (HU) of the segmented SMA. SMM and SMD were categorized as low, intermediate, and high, based on LSMI and mean HU tertiles, respectively. Chemotherapy‐induced toxicity was scored using CTCAE v4.03 and categorized into haematological (anaemia, leukocytopenia, neutropenia, and thrombocytopenia), non‐haematological (nephrotoxicity, neurotoxicity, and esophagitis), and dose‐limiting toxicity (DLT) (treatment switch, delay, de‐escalation, discontinuation, or hospitalization). The relationship between SMM, SMD, and toxicities was assessed with logistic regression modelling taking into account potential confounders like gender and body mass index (BMI). Results In total, 297 patients (male n = 167, median age 64 years) were included. Haematological toxicity grade 3/4 was experienced in 36.6% (n = 108) of the patients, 24.6% (n = 73) experienced any non‐haematological toxicity grade ≥2, and 55.6% (n = 165) any DLT. Multivariate logistic regression analysis showed that low SMM (ORadj 2.41, 95% CI 1.31–4.45, P = 0.005) and age at diagnosis >65 years (ORadj 1.76, 95% CI 1.07–2.90, P = 0.025) were statistically significantly associated with overall haematological toxicity grade 3/4. No statistically significant associations were found between low SMM or low SMD and non‐haematological toxicities. Low SMM (ORadj 2.23, 95% CI 1.23–4.04, P = 0.008) and high SMD (ORadj 0.41, 95% CI 0.23–0.74, P = 0.003) were statistically significantly associated with a higher respectively lower risk of DLT. Conclusions Non‐small cell lung cancer patients with pretreatment low SMM are at significant higher risk for haematological toxicities grade 3/4 and DLT. NSCLC patients with high SMD are at significant lower risk for DLT. Further studies should be aimed to investigate whether platinum dosing based on skeletal muscle measurements and/or improvement of pretreatment SMM/SMD could reduce the risk of toxicity without compromising efficacy.

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Section: Discussionmentioning

confidence: 99%

The association between skeletal muscle measures and chemotherapy‐induced toxicity in non‐small cell lung cancer patients

Jong

Chargi

Herder

et al. 2022

J cachexia sarcopenia muscle

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“…A previous study presented that the clearance of cisplatin and paclitaxel was increased in obese patients [ 123 ]. However, underlying mechanisms for the effect of obesity on treatment outcome are currently unknown [ 123 ], and a study in patients receiving paclitaxel for esophageal cancer reported that paclitaxel dosing could not be optimized by correcting for body composition [ 124 ]. Future studies should identify if body composition measures have prognostic value for specific toxicities in patients with ovarian cancer.…”

Section: Discussionmentioning

confidence: 99%

Association between Energy Balance-Related Factors and Clinical Outcomes in Patients with Ovarian Cancer: A Systematic Review and Meta-Analysis

Stelten

Schofield

Hartman

et al. 2022

Cancers

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Background: This systematic review and meta-analysis synthesized evidence in patients with ovarian cancer at diagnosis and/or during first-line treatment on; (i) the association of body weight, body composition, diet, exercise, sedentary behavior, or physical fitness with clinical outcomes; and (ii) the effect of exercise and/or dietary interventions. Methods: Risk of bias assessments and best-evidence syntheses were completed. Meta-analyses were performed when ≥3 papers presented point estimates and variability measures of associations or effects. Results: Body mass index (BMI) at diagnosis was not significantly associated with survival. Although the following trends were not supported by the best-evidence syntheses, the meta-analyses revealed that a higher BMI was associated with a higher risk of post-surgical complications (n = 5, HR: 1.63, 95% CI: 1.06–2.51, p = 0.030), a higher muscle mass was associated with a better progression-free survival (n = 3, HR: 1.41, 95% CI: 1.04–1.91, p = 0.030) and a higher muscle density was associated with a better overall survival (n = 3, HR: 2.12, 95% CI: 1.62–2.79, p < 0.001). Muscle measures were not significantly associated with surgical or chemotherapy-related outcomes. Conclusions: The prognostic value of baseline BMI for clinical outcomes is limited, but muscle mass and density may have more prognostic potential. High-quality studies with comprehensive reporting of results are required to improve our understanding of the prognostic value of body composition measures for clinical outcomes. Systematic review registration number: PROSPERO identifier CRD42020163058.

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Feasibility of pharmacometabolomics to identify potential predictors of paclitaxel pharmacokinetic variability

Chen

Sun

et al. 2021

Cancer Chemother Pharmacol

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The Influence of Body Composition on the Systemic Exposure of Paclitaxel in Esophageal Cancer Patients

Cited by 5 publications

References 26 publications

The association between skeletal muscle measures and chemotherapy‐induced toxicity in non‐small cell lung cancer patients

The association between skeletal muscle measures and chemotherapy‐induced toxicity in non‐small cell lung cancer patients

Association between Energy Balance-Related Factors and Clinical Outcomes in Patients with Ovarian Cancer: A Systematic Review and Meta-Analysis

Feasibility of pharmacometabolomics to identify potential predictors of paclitaxel pharmacokinetic variability

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