Haematological toxicity of pemetrexed in patients with metastatic non-squamous non-small cell carcinoma of lung with third-space fluid

Kwok, Wang Chun; Cheong, Tan Fong; Chiang, Ka Yan; Ho, James Chung Man; Lam, David; Ip, Mary Sau Man; Tam, Terence Chi Chun

doi:10.1016/j.lungcan.2020.11.028

Cited by 4 publications

(2 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For methotrexate, another antifolate, structurally similar to pemetrexed, a toxicity threshold was previously identified in patients receiving high-dose treatment, 22 further supporting the plausibility that pemetrexed-induced neutropenia is also dependent on such a threshold-driven relationship. This finding may explain recent findings by Kwok and colleagues, 23 who found that presence of third space fluid during treatment with pemetrexed is a significant risk factor for this toxicity. Presence of third space fluid may result in an increase of a peripheral compartment volume, F I G U R E 3 Typical absolute neutrophil count curves for vitamin-supplemented patients according to the model with a threshold-driven exposure-toxicity relationship.…”

Section: Discussionsupporting

confidence: 71%

Toxicity of pemetrexed during renal impairment explained—Implications for safe treatment

Boosman

Dorlo

Rouw

et al. 2021

Intl Journal of Cancer

View full text Add to dashboard Cite

Pemetrexed is an important component of first line treatment in patients with non‐squamous non‐small cell lung cancer. However, a limitation is the contraindication in patients with renal impairment due to hematological toxicity. Currently, it is unknown how to safely dose pemetrexed in these patients. The aim of our study was to elucidate the relationship between pemetrexed exposure and toxicity to support the development of a safe dosing regimen in patients with renal impairment. A population pharmacokinetic/pharmacodynamic analysis was performed based on phase II study results in three patients with renal dysfunction, supplemented with data from 106 patients in early clinical studies. Findings were externally validated with data of different pemetrexed dosing regimens. Alternative dosing regimens were evaluated using the developed model. We found that pemetrexed toxicity was driven by the time above a toxicity threshold concentration. The threshold for vitamin‐supplemented patients was 0.110 mg/mL (95% CI: 0.092‐0.146 mg/mL). It was observed that in patients with renal impairment (estimated glomerular filtration rate [eGFR]: <45 mL/min) the approved dose of 500 mg/m2 would yield a high probability of severe neutropenia in the range of 51.0% to 92.6%. A pemetrexed dose of 20 mg for patients (eGFR: 20 mL/min) is shown to be neutropenic‐equivalent to the approved dose in patients with adequate renal function (eGFR: 90 mL/min), but would result in an approximately 13‐fold lower area under the concentration‐time curve. The pemetrexed exposure‐toxicity relationship is explained by a toxicity threshold and substantially different from previously thought. Without prophylaxis for toxicity, it is unlikely that a therapeutic dose can be safely administered to patients with renal impairment.

show abstract

Section: Discussionsupporting

confidence: 71%

Toxicity of pemetrexed during renal impairment explained—Implications for safe treatment

Boosman

Dorlo

Rouw

et al. 2021

Intl Journal of Cancer

View full text Add to dashboard Cite

show abstract

“…The term "NSCLC-non-squamous cell carcinoma" should be avoided as a histopathologic diagnosis, as this entity is used by clinicians to describe a heterogeneous group of tumors for clinical trials. [4][5][6] A few entities require a resection specimen to diagnose, including adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma; in these scenarios, the tumor should be diagnosed as adenocarcinoma with a lepidic growth pattern only if a noninvasive pattern is present, with a comment that definitive diagnosis is deferred to a larger specimen.…”

Section: Small Diagnostic Samplesmentioning

confidence: 99%

An Update on the Classification of Lung and Pleural Tumors

Liang¹,

Xu²

2023

J Clin Transl Pathol

View full text Add to dashboard Cite

The World Health Organization (WHO) recently published new guidelines for the diagnosis and classification of lung and pleural tumors. This review provides a concise overview of the key updates, including discussions of histologic features and recommended terminology for small diagnostic lung samples, the revised grading system for lung adenocarcinoma with inclusion of complex glandular and filigree micropapillary patterns, and molecular features of large cell neuroendocrine carcinoma. Additionally, rare neoplasms such as bronchiolar adenoma/ciliated muconodular papillary tumor, SMARCA4-deficient undifferentiated thoracic tumor, and primary pulmonary hyalinizing clear cell carcinoma are described in terms of their diagnostic approaches and molecular features. This review also includes discussion of the diagnostic algorithm for malignant epithelioid mesothelioma.

show abstract

Risk factors of nephrotoxicity of maintenance pemetrexed in patients with metastatic non-squamous non-small cell carcinoma of lung

Kwok

Chiang

et al. 2021

Lung Cancer

View full text Add to dashboard Cite

Haematological toxicity of pemetrexed in patients with metastatic non-squamous non-small cell carcinoma of lung with third-space fluid

Cited by 4 publications

References 26 publications

Toxicity of pemetrexed during renal impairment explained—Implications for safe treatment

Toxicity of pemetrexed during renal impairment explained—Implications for safe treatment

An Update on the Classification of Lung and Pleural Tumors

Risk factors of nephrotoxicity of maintenance pemetrexed in patients with metastatic non-squamous non-small cell carcinoma of lung

Contact Info

Product

Resources

About