The association of cisplatin pharmacokinetics and skeletal muscle mass in patients with head and neck cancer: The prospective PLATISMA study

Chargi, Najiba; Molenaar-Kuijsten, Laura; Huiskamp, Laura F.J.; Devriese, Lot A.; Bree, Remco de; Huitema, Alwin D. R.

doi:10.1016/j.ejca.2021.10.010

Cited by 16 publications

(12 citation statements)

References 22 publications

(22 reference statements)

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“…Williams et al found a significant positive association of LBM and oxaliplatin clearance and LBM and volume of distribution as well as a significant association of low LBM and high‐grade toxicity in older patients with colorectal cancer. Similar results were identified for cisplatin even though dose‐limiting toxicity was not significantly correlated with body composition 53 . Our finding of a higher probability of the occurrence of clinically relevant polyneuropathy with decreasing SMI of the back muscle deserves further investigation.…”

Section: Discussionsupporting

confidence: 80%

“…Similar results were identified for cisplatin even though dose‐limiting toxicity was not significantly correlated with body composition. 53 Our finding of a higher probability of the occurrence of clinically relevant polyneuropathy with decreasing SMI of the back muscle deserves further investigation. Since the psoas muscle is necessary for everyday movement, the reduction of its SMI may be an explanation for the identified increase in the probability of clinically relevant fatigue.…”

Section: Discussionmentioning

confidence: 71%

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Influence of the skeletal muscle index on pharmacokinetics and toxicity of fluorouracil

et al. 2022

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Background The body composition of patients has been associated with tolerability and effectiveness of anticancer therapy. This study aimed to assess the influence of the skeletal muscle index (SMI) on the pharmacokinetics and toxicity of fluorouracil. Methods Patients treated in an oncological practice with fluorouracil‐based chemotherapy and undergoing therapeutic drug monitoring were retrospectively investigated. Computed tomography images were analyzed to measure abdominal skeletal muscle areas in Hounsfield units for the psoas major muscle, back and total skeletal muscle to determine the SMI. For the latter, an automated segmentation method was used additionally. SMI measures were tested as covariates on fluorouracil clearance in a population pharmacokinetic model. Furthermore, regression analyses were performed to analyze the influence of SMI measures on the probability of clinically relevant adverse events (CTCAE grades ≥ 2). Results Fluorouracil plasma concentrations of 111 patients were available. Covariate analyses showed significant improvements of the model fit by all SMI measures. However, interindividual variability of fluorouracil clearance was only slightly reduced, whereas the SMI of the back muscle showed the largest reduction (−1.1 percentage points). Lower SMI values of the back muscle increased the probability for polyneuropathy and lower SMI of the psoas increased the probability for fatigue. Conclusions Our results suggest that pharmacokinetics and toxicity of fluorouracil may be associated with specific SMI measures which deserve further investigation.

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Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 71%

Influence of the skeletal muscle index on pharmacokinetics and toxicity of fluorouracil

et al. 2022

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“…In addition, several other potential confounding covariates (e.g. serum albumin, hemoglobin value, skeletal mass) that were previously associated with cisplatin PK or its safety profile, have not been assessed by any of the studies and might need further evaluation in cisplatin-based management of SCLC [39][40][41].…”

Section: Discussionmentioning

confidence: 99%

Population pharmacokinetics of cisplatin in small cell lung cancer patients guided with informative priors

Zdovc

Vaupotič

Marolt

et al. 2022

Cancer Chemother Pharmacol

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Purpose Cisplatin-etoposide treatment is recommended as a first line in small cell lung cancer patients (SCLC). However, the prognosis is poor and the dosing is not tailored beyond the body surface area, which is related with indeterminate cisplatin exposure-response relationship. We aimed to evaluate cisplatin pharmacokinetics (PK) and the exposure to unbound cisplatin in SCLC patients using the informative priors, and assess the relationship between the cisplatin exposure and probability of neutropenia. Methods Observational clinical study was performed including 17 cisplatin-treated SCLC patients. External population cisplatin PK models were identified and NONMEM ® software and $PRIOR subroutine were used for the model evaluation. The bias and precision of the model-predicted cisplatin concentrations were evaluated. The best models were combined in a final model including several sets of informative priors, which was used to estimate individual cisplatin exposure, analyze the relationship between the exposure and neutropenia and simulate several cisplatin dosing regimens in a virtual patient cohort. ResultsThe models by Urien with the informative priors best fitted the data. The individual cisplatin exposure ranged between 2430 and 4560 μg*h/L. There was a trend of increasing probability of neutropenia and febrile neutropenia with increasing cisplatin exposure. Approximately 50%, 75% and 90% of patients receiving 60 mg/m 2 , 70 mg/m 2 and 80 mg/m 2 , respectively, achieved the previously identified exposure threshold of 2860 μg*h/L. Conclusion We developed a tool to individualize cisplatin dosing based on the estimated probability of neutropenia. The benefit of more intense dosing regimens in SCLC patients should be further assessed.

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“…It is hypothesized that an altered distribution of cisplatin, which is reflected by differences in cisplatin plasma concentrations, could explain why patients with low SMM are more prone to experience cisplatin toxicity. In a prospective study by Chargi et al [33], a significant relationship between cisplatin pharmacokinetics and SMM, weight, fat-free mass, and body surface area was found in 45 HNC patients. In a simulation, patients with a low SMM (<25.8 kg) were predicted to reach higher-bound cisplatin concentrations.…”

Section: Toxicity Of Anti-cancer Drugsmentioning

confidence: 95%

“…The higher concentration of bound cisplatin could be seen as a reflection of the smaller volume of distribution. Because of this smaller volume, less tissue is available where, the hydrophilic and highly reactive cisplatin can distribute to and bind with, without inducing toxicity [33].…”

Section: Toxicity Of Anti-cancer Drugsmentioning

confidence: 99%

Sarcopenia and its impact in head and neck cancer treatment

Bree

Beers

Schaeffers

2022

Current Opinion in Otolaryngology &Amp; Head &Amp; Neck Surgery

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Purpose of reviewThe aim of this review is to discuss recent studies on the assessment of sarcopenia and its predictive and prognostic value in head and neck cancer (HNC) patients. Recent findingsThere is increasing evidence that low skeletal muscle mass (SMM), often named sarcopenia, can easily be assessed on cross-sectional imaging of the head and neck and is associated with chemotherapy (dose limiting) and radiotherapy toxicity and survival. SummarySMM measurement at the level of the third cervical vertebra (C3) on routine computed tomography and magnetic resonance imaging is easy and robust to perform. Several studies have shown a significantly higher incidence of cisplatin dose limiting toxicity in HNC patients with a low SMM. In HNC patients pretreatment low SMM is associated with acute and late toxicity and adverse events of radiotherapy, complications of major head and neck surgery and decreased disease-specific and overall survival. This information can be used for individualized treatment planning in HNC patients with low SMM.

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The association of cisplatin pharmacokinetics and skeletal muscle mass in patients with head and neck cancer: The prospective PLATISMA study

Cited by 16 publications

References 22 publications

Influence of the skeletal muscle index on pharmacokinetics and toxicity of fluorouracil

Influence of the skeletal muscle index on pharmacokinetics and toxicity of fluorouracil

Population pharmacokinetics of cisplatin in small cell lung cancer patients guided with informative priors

Sarcopenia and its impact in head and neck cancer treatment

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