Everolimus pharmacokinetics and exposure-response relationship in Japanese patients with advanced breast cancer

Hirabatake, Masaki; Mizuno, Tomoyuki; Kato, Hironori; Hashida, Tohru

doi:10.3389/fphar.2022.984002

Cited by 5 publications

(4 citation statements)

References 34 publications

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“…In another study by Hirabatake et al median PFS was 13.7 months (1.7-55.8 months) and fifty per cent of breast cancer patients treated with everolimus showed Css below 10ng/ml. PFS was significantly longer in the 10-20ng/ml group (p=0.0078) and the median of Cminss in patients with dose-limiting toxicities was 19ng/ml (11.3-64.6ng/ml) 12 .…”

Section: Discussionmentioning

confidence: 93%

Everolimus Therapeutic Drug Monitoring in a Cancer Renal Cancer Patient When Double Drug-Drug Interaction Is Detected and a Review of the Literature

Casamartina

Sánchez

Rigo-Bonnin

et al. 2023

Preprint

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Everolimus is an inhibitor of mammalian target of rapamycin (mTOR) widely used as an immunosuppressant in transplant patients. In transplantation setting, several recommendations for therapeutic drug monitoring are available, due to potential drug-drug interactions with chronic medication, which can affect everolimus pharmacokinetic profile. Everolimus is also used in breast, neuroendocrine and renal cancer, at higher doses than in transplantation and without systematic drug monitoring requirement. We present a case-report of a 72years-old woman with epilepsy history to whom everolimus 10mg/daily was prescribed as third line of treatment for renal cell carcinoma. The patient´s chronic medication was checked by the outpatient hospital pharmacist before initiating treatment. As a result, two major interactions with inducers of CYP3A4 metabolism as carbamazepine and phenytoin were detected. Since trough plasma concentration of everolimus could be affected, by these pharmacokinetic interactions,a therapeutic drug monitoring of everolimus was proposed. Based on the literature, Cmin plasma concentration (Cminss) of everolimus over 10ng/ml is associated with better response to treatment and progression free survival. During the oncologist follow-up visit and according to pharmaceutical recommendations, everolimus dosage was increased to 10mg every 12 hours. In the following determinations of trough plasma everolimus concentration, Cmin grow up from 3.7ng/ml to 10.8ng/mL. Depending on the CYP3A4 induction capacity and potency of the drug/s administered concomitant to everolimus and how many of them can potentially interact with it, therapeutic everolimus monitoring would be advisable in order to adjust dosage if required to prevent underexposure.

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Section: Discussionmentioning

confidence: 93%

Everolimus Therapeutic Drug Monitoring in a Cancer Renal Cancer Patient When Double Drug-Drug Interaction Is Detected and a Review of the Literature

Casamartina

Sánchez

Rigo-Bonnin

et al. 2023

Preprint

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show abstract

“…In another study by Hirabatake et al median PFS was 13.7 months (1.7–55.8 months) and 50% of breast cancer patients treated with everolimus showed Cminss below 10 ng/ml. PFS was significantly longer in the 10-20 ng/ml group ( p = 0.0078) and the median of Cminss in patients with dose-limiting toxicities was 19 ng/ml (11.3–64.6 ng/ml) [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

First reported double drug–drug interaction in a cancer renal patient under everolimus treatment: therapeutic drug monitoring and review of literature

Fort-Casamartina,

Muñoz-Sanchez,

Rigo-Bonnin

et al. 2023

Eur J Med Res

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Everolimus is an inhibitor of mammalian target of rapamycin (mTOR) used in both transplantation and cancer treatment (breast, renal and neuroendocrine). In transplantation, therapeutic drug monitoring (TDM) is recommended due to the potential drug–drug interactions with chronic medications, which can affect everolimus pharmacokinetics. In cancer treatment, everolimus is used at higher doses than in transplantation and without a systematic drug monitoring.We present a case report of a 72-year-old woman with epilepsy history to whom everolimus 10 mg QD was prescribed as third line of treatment for renal cell carcinoma (RCC). The potential drug interactions between everolimus and the patient's chronic medications, carbamazepine and phenytoin, are significant as both are known as strong inducers CYP3A4 metabolism, potentially leading to underexposure to everolimus.TDM of everolimus was recommended by the pharmacist. The literature suggests that a minimum plasma concentration (Cminss) of everolimus over 10 ng/ml is associated with better response to treatment and progression-free survival (PFS). The patient’s everolimus dose had to be increased until 10 mg BID, and regular monitoring of everolimus levels showed an increase in Cminss from 3.7 ng/ml to 10.8 ng/ml.This case highlights the importance of checking for potential drug interactions and monitoring everolimus levels in patients on chronic medication, especially those with several inducers or inhibitors of CYP3A4 metabolism. TDM can help to ensure that patients are treated with their optimal dose, which can improve the effectiveness of the treatment or minimize the risk of toxicities.

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“…Table 3 shows the detailed validation results and the missing parameter data of other neutral drugs. Most neutral drugs that underwent a validation study have an LLOQ concentration below the plasma/serum concentration range of their drugs, except for everolimus, perampanel, and sirolimus [ 16 , 53 , 61 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 ]. Everolimus has an LLOQ of 0.02 µg/mL [ 61 ], whereas its concentration range is 0.003–0.008 µg/mL [ 100 ].…”

Section: Analytical Validation Of Volumetric Absorptive Microsampling...mentioning

confidence: 99%

“…Most neutral drugs that underwent a validation study have an LLOQ concentration below the plasma/serum concentration range of their drugs, except for everolimus, perampanel, and sirolimus [ 16 , 53 , 61 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 ]. Everolimus has an LLOQ of 0.02 µg/mL [ 61 ], whereas its concentration range is 0.003–0.008 µg/mL [ 100 ]. The LLOQ of perampanel was 0.022 µg/mL [ 16 ], and its concentration range was 0.019–2.436 µg/mL [ 104 ].…”

Section: Analytical Validation Of Volumetric Absorptive Microsampling...mentioning

confidence: 99%

Analytical and Clinical Validation of Assays for Volumetric Absorptive Microsampling (VAMS) of Drugs in Different Blood Matrices: A Literature Review

et al. 2023

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Volumetric absorptive microsampling (VAMS) is the newest and most promising sample-collection technique for quantitatively analyzing drugs, especially for routine therapeutic drug monitoring (TDM) and pharmacokinetic studies. This technique uses an absorbent white tip to absorb a fixed volume of a sample (10–50 µL) within a few seconds (2–4 s), is more flexible, practical, and more straightforward to be applied in the field, and is probably more cost-effective than conventional venous sampling (CVS). After optimization and validation of an analytical method of a drug taken by VAMS, a clinical validation study is needed to show that the results by VAMS can substitute what is gained from CVS and to justify implementation in routine practice. This narrative review aimed to assess and present studies about optimization and analytical validation of assays for drugs taken by VAMS, considering their physicochemical drug properties, extraction conditions, validation results, and studies on clinical validation of VAMS compared to CVS. The review revealed that the bio-analysis of many drugs taken with the VAMS technique was optimized and validated. However, only a few clinical validation studies have been performed so far. All drugs that underwent a clinical validation study demonstrated good agreement between the two techniques (VAMS and CVS), but only by Bland–Altman analysis. Only for tacrolimus and mycophenolic acid were three measurements of agreement evaluated. Therefore, VAMS can be considered an alternative to CVS in routine practice, especially for tacrolimus and mycophenolic acid. Still, more extensive clinical validation studies need to be performed for other drugs.

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Everolimus pharmacokinetics and exposure-response relationship in Japanese patients with advanced breast cancer

Cited by 5 publications

References 34 publications

Everolimus Therapeutic Drug Monitoring in a Cancer Renal Cancer Patient When Double Drug-Drug Interaction Is Detected and a Review of the Literature

Everolimus Therapeutic Drug Monitoring in a Cancer Renal Cancer Patient When Double Drug-Drug Interaction Is Detected and a Review of the Literature

First reported double drug–drug interaction in a cancer renal patient under everolimus treatment: therapeutic drug monitoring and review of literature

Analytical and Clinical Validation of Assays for Volumetric Absorptive Microsampling (VAMS) of Drugs in Different Blood Matrices: A Literature Review

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