Abstract 4652: Cerebrospinal fluid pharmacokinetics and pharmacodynamics following high-dose erlotinib treatment in brain cancer patients

Brain cancers are among the top causes of death worldwide. Although, the survival rates vary widely depending on the type of the tumor, early diagnosis could generally benefit in better prognosis outcomes of the brain cancer patients. Conventionally, neuroimaging and biopsy are the most widely used approaches in diagnosis, subtyping, and prognosis monitoring of brain cancers, while emerging liquid biopsy assays using peripheral blood or cerebrospinal fluid have demonstrated many favorable characteristics in this task, especially due to their minimally invasive and easiness in sampling nature. Here, we review the recent studies in the liquid biopsy of brain cancers. We discuss the methodologies and performances of various assays on diagnosis, tumor subtyping, relapse prediction as well as prognosis monitoring in brain cancers, which approaches have made a big step toward clinical benefits of brain cancer patients.

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CSF pharmacokinetics of high-dose pulsatile tyrosine kinase therapy in brain cancer patients.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.15_suppl.e13032 ◽

2015 ◽

Vol 33 (15_suppl) ◽

pp. e13032-e13032

Author(s):

Sandeep C. Pingle ◽

Tiffany Juarez ◽

Marlon G. Saria ◽

Santosh Kesari

Keyword(s):

Tyrosine Kinase ◽

Cancer Patients ◽

Brain Cancer ◽

High Dose ◽

Csf Pharmacokinetics

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The Effectiveness of High-dose Intravenous Vitamin c With Very Low Carbohydrate Diet for Terminal Colon Cancer Patients

Case Medical Research ◽

10.31525/ct1-nct04035096 ◽

2019 ◽

Author(s):

Keyword(s):

Colon Cancer ◽

Vitamin C ◽

Cancer Patients ◽

High Dose ◽

Carbohydrate Diet ◽

Low Carbohydrate Diet ◽

Low Carbohydrate ◽

Intravenous Vitamin

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THE PREVALENCE OF HEPATITIS B REACTIVATION (HBV) IN CANCER PATIENTS TREATING WITH CHEMOTHERAPY

Journal of Medicine and Pharmacy ◽

10.34071/jmp.2016.1.9 ◽

2016 ◽

pp. 74-80

Author(s):

Phuong Phung ◽

Thi Thuy Nguyen

Keyword(s):

Breast Cancer ◽

Lung Cancer ◽

Hepatitis B ◽

Cancer Patients ◽

Positive Control ◽

High Dose ◽

Hbv Reactivation ◽

Endemic Region ◽

Hepatitis B Reactivation ◽

Cancer Breast

ackground and Objectives: Nowadays, the incidence of cancer is constantly increasing in the world as well as in Vietnam. The treatment of cancer is based on multimodality principle. Among those principal modalities, chemotherapy is widely used for different purposes such as neoadjuvant, andjuvant and palliation. However, chemotherapy can induce activation of latent infections, including hepatitis B. Vietnam is in the endemic region of hepatitis B so the reactivation of hepatitis B on cancer patients with chemotherapy has emerged a concerned problem. However, few interests were gained on this problem in the aspect of clinical setting or researching. Aims: to determine the prevalence of hepatitis B reactivation (HBV) in cancer patients treating with chemotherapy and to detect some risks factors of this situation. Subjects and methods: descriptive prospective. The study included 33 cancer patients with inactive HBV infection who are treating with chemotherapy. We define HBV reactivation by ALT > 3 ULN and HBV DNA copies > 10 positive control limit. Results: We found 6 patients with reactivated HBV, accounting for 18.18 %. Among reactivated HBV patients, age less than 60 accounts 83,33%. Rate of reactivated HBV in males was 25,00% while this rate in females was 14,28%. Rate of reactivated HBV in lymphoma, lung cancer and breast cancer was 33,33%, 25% và 22,22% respectively. Clinial manifestation of reactivated HBV includes jaundice (33,33%), fulminant hepatic failure (6%) and death (5%). The reactivated rate was higher in patients got high dose of corticoid (28,57%) vs low dose (15,38%). This rate was 29,41% in patients treated with anthracyclines which was higher than in group without anthracyclines. The reactivated rate of HBV was dramatically higher in patients treated with rituximab (75%). Conclusion: the reactivation of hepatitis B on cancer patients with chemotherapy is common. We found 6 patients with reactivated HBV of 33 subjects of the study which accounts 18.18 %. We recognized that reactivated HBV rate was higher subgroups of age < 60 years old, males, patients with lymphoma, lung cancer, breast cancer. Reactivated HBV may be more prevalent in patients with high-dose corticotherapy, anthracyclines and Rituximab. Key words: HBV reactivation, chemotherapy, cancer, hepatitis B

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274 High-dose medroxyprogesterone acetate (MPA) in metastatic cancer patients

Journal of Steroid Biochemistry ◽

10.1016/0022-4731(83)91774-0 ◽

1983 ◽

Vol 19 ◽

pp. 91

Author(s):

P. Schmidt-Rhode ◽

G. Sturm ◽

K.-D. Schulz ◽

H.J. Künzig ◽

M. Wunsch

Keyword(s):

Cancer Patients ◽

Medroxyprogesterone Acetate ◽

Metastatic Cancer ◽

High Dose

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ctDNA-Based Liquid Biopsy of Cerebrospinal Fluid in Brain Cancer

Cancers ◽

10.3390/cancers13091989 ◽

2021 ◽

Vol 13 (9) ◽

pp. 1989

Author(s):

Laura Escudero ◽

Francisco Martínez-Ricarte ◽

Joan Seoane

Keyword(s):

Cerebrospinal Fluid ◽

Brain Cancer ◽

Liquid Biopsy ◽

Therapeutic Strategy ◽

Residual Disease ◽

Imaging Techniques ◽

Prognostic Information ◽

Tumour Heterogeneity ◽

Diagnosis And Prognosis ◽

Cns Malignancies

The correct characterisation of central nervous system (CNS) malignancies is crucial for accurate diagnosis and prognosis and also the identification of actionable genomic alterations that can guide the therapeutic strategy. Surgical biopsies are performed to characterise the tumour; however, these procedures are invasive and are not always feasible for all patients. Moreover, they only provide a static snapshot and can miss tumour heterogeneity. Currently, monitoring of CNS cancer is performed by conventional imaging techniques and, in some cases, cytology analysis of the cerebrospinal fluid (CSF); however, these techniques have limited sensitivity. To overcome these limitations, a liquid biopsy of the CSF can be used to obtain information about the tumour in a less invasive manner. The CSF is a source of cell-free circulating tumour DNA (ctDNA), and the analysis of this biomarker can characterise and monitor brain cancer. Recent studies have shown that ctDNA is more abundant in the CSF than plasma for CNS malignancies and that it can be sequenced to reveal tumour heterogeneity and provide diagnostic and prognostic information. Furthermore, analysis of longitudinal samples can aid patient monitoring by detecting residual disease or even tracking tumour evolution at relapse and, therefore, tailoring the therapeutic strategy. In this review, we provide an overview of the potential clinical applications of the analysis of CSF ctDNA and the challenges that need to be overcome in order to translate research findings into a tool for clinical practice.

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Pharmacokinetics and Pharmacodynamics of High-Dose Piperacillin–Tazobactam in Obese Patients

European Journal of Drug Metabolism and Pharmacokinetics ◽

10.1007/s13318-021-00677-1 ◽

2021 ◽

Author(s):

John J. Veillette ◽

S. Alexander Winans ◽

Victoria K. Maskiewicz ◽

James Truong ◽

Ronald N. Jones ◽

...

Keyword(s):

High Dose ◽

Obese Patients ◽

Pharmacokinetics And Pharmacodynamics

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Intranasal administration of the chemotherapeutic perillyl alcohol results in selective delivery to the cerebrospinal fluid in rats

Scientific Reports ◽

10.1038/s41598-021-85293-4 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Geetika Nehra ◽

Shannon Andrews ◽

Joan Rettig ◽

Michael N. Gould ◽

Jill D. Haag ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Brain Tumors ◽

Nasal Mucosa ◽

Brain Cancer ◽

Intranasal Administration ◽

High Performance ◽

Early Stage ◽

Plasma Concentrations ◽

Perillyl Alcohol ◽

Systemic Absorption

AbstractPerillyl alcohol (POH) has been extensively studied for the treatment of peripheral and primary brain tumors. The intranasal route of administration has been preferred for dosing POH in early-stage clinical trials associated with promising outcomes in primary brain cancer. However, it is unclear how intranasal POH targets brain tumors in these patients. Multiple studies indicate that intranasally applied large molecules may enter the brain and cerebrospinal fluid (CSF) through direct olfactory and trigeminal nerve-associated pathways originating in the nasal mucosa that bypass the blood–brain barrier. It is unknown whether POH, a small molecule subject to extensive nasal metabolism and systemic absorption, may also undergo direct transport to brain or CSF from the nasal mucosa. Here, we compared CSF and plasma concentrations of POH and its metabolite, perillic acid (PA), following intranasal or intravascular POH application. Samples were collected over 70 min and assayed by high-performance liquid chromatography. Intranasal administration resulted in tenfold higher CSF-to-plasma ratios for POH and tenfold higher CSF levels for PA compared to equal dose intravascular administration. Our preclinical results demonstrate POH undergoes direct transport from the nasal mucosa to the CSF, a finding with potential significance for its efficacy as an intranasal chemotherapeutic for brain cancer.

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