Nutritional and Metabolic Diseases

All Conditions

Symptoms and General Pathology

Wasting Syndrome

Cachexia

Syndrome

Body Weight

Weight Loss

Body Weight Changes

Thinness

Metabolic Diseases

Nutrition Disorders

Gastrointestinal Agents

All Drugs and Chemicals

Herbal and Botanical

Pancrelipase

Pancreatin

Cola

Cachectic lung, pancreas, or colon cancer patients.

Non- cachectic lung, pancreas, or colon cancer patients.

Pharmacogenetic testing

Rana M. Yehia, MSc

Dr. Amr Shafik, PhD

Cachexia not only directly increases the morbidity and mortality, it also aggravates the side effects of chemotherapy and reduces the overall quality of life that is often considered the major and direct cause of morbidity of a large proportion (\>40%) of cancer patients. Individuals with upper gastrointestinal tumors have the highest rate of developing cachexia associated complications. Chemical and physical signals render an environment conducive for disuse and untenable for proper muscle function leading to wasting.

Till now, several functional single-nucleotide polymorphisms (SNPs) within TNF-α gene have been identified and described as cancer related genetic alterations.

Cachexia is a devastating syndrome that is observed in the majority of end stage cancer patients. Primary symptoms of cancer cachexia comprise of progressive loss in weight and exhaustion of host skeletal muscle tissue as well as adipose tissue reserves.

Cancer cachexia is defined as a multifactorial syndrome, characterized by anorexia as well as diminished body weight, loss of skeletal muscle, and atrophy of adipose tissue (Fearon et al., 2011). Specifically, weight loss of more than 5% over 6 months span in previously healthy individuals or more than 2% in subjects with depletion of current body weight (BMI less than 20 kg/m2) or in individuals with reduced appendicular muscle index (males less than 7.26 kg/m2 and females less than 5.45 kg/m2) constitute the diagnosis of cancer cachexia.

Among potential mechanisms involved in the development of cachexia, the primary initial process is probably the systemic inflammatory response followed by increased production of pro-inflammatory cytokines, such as TNF-α. Multiple biological activities of TNF-α were found in numerous physiological states, including the regulation of cell differentiation, proliferation, apoptosis and metabolism .

A heparinized blood sample (5 mls) will be withdrawn from all patients, and divided in 2 aliquots. One aliquot will be spared for DNA and the other for RNA extraction.

Effect of Gene Polymorphisms on the Pathogenesis of Cancer Cachexia

Relationship Between TNF Alpha Gene Polymorphisms and the Pathogenesis of Cachexia in Cancer Patients Treated With Chemotherapy

To detect the incidence of tumor necrosis factor (TNF-α -1031T/C and 308 G/A) gene polymorphism in the Egyptian cancer patients with local/advanced or metastatic cancer and investigation of TNF-α -1031T/C and 308 G/A as a cachexia risk factor.

Misr International University

Ain Shams University

Cairo University

Professor of Pharmacology

Catastrophic Illness

Disease Attributes

All participants enrolled on this study will have blood drawn for genetic testing.

Clinton F. Stewart, Pharm.D.

Jun J. Yang, Ph.D.

To investigate whether genetic polymorphisms in genes encoding proteins involved in the metabolism or effects of drugs or environmental agents influence the disposition or effects of these xenobiotic substrates. To investigate the nature of heritability and the genetic basis of pharmacogenetic traits by studying family members of individuals with specific genotypes.

Pharmacogenetics is that discipline devoted to elucidating the genetic determinants of drug response. Particularly in the area of drug metabolism, many genes exhibit genetic polymorphism; that is, a stable percentage of the population (which generally differs by ethnic group) is deficient in the functional expression of the enzyme involved, and the deficiency is typically inherited as an autosomal recessive trait. With currently known polymorphisms in drug metabolism, the percentage of homozygous deficient individuals ranges from 0.3% to as many as 90% of the population, depending on the enzyme and the ethnic group.

Our prior studies have revealed multigenic pharmacogenetic models that are significantly predictive of various drug response phenotypes (e.g., drug resistance, drug clearance, drug toxicity, disease response) in children with ALL. The large number of candidate loci and the relatively small number of patients illustrate the fact that larger sample sizes are required to definitively establish these polygenic models. The fact that there were significant race/genotype interactions, such that predictions differed in whites vs blacks, highlights the need for adequate numbers of patients within racial and ethnic groups to allow differential analysis of genotypic predictors after adjusting for confounding demographic factors in pharmacogenetic studies via stratified design and analyses.

DNA or RNA for genetic testing will typically be obtained simultaneously with blood that is drawn for clinical reasons.

Pharmacogenetic Determinants Of Treatment Response In Children

National Cancer Institute (NCI)

National Institute of General Medical Sciences (NIGMS)

St. Jude Children's Research Hospital

Behaviors and Mental Disorders

Nervous System Diseases

Wounds and Injuries

Depression

Depressive Disorder

Cancer Pain

Pain

Nausea

Vomiting

Adjustment Disorders

Signs and Symptoms, Digestive

Neurologic Manifestations

Trauma and Stressor Related Disorders

Mental Disorders

Psychotic Disorders

Analgesics

Central Nervous System Depressants

Antiemetics

Dermatologic Agents

Vasoconstrictor Agents

Psychotropic Drugs

Anti-Dyskinesia Agents

Antitussive Agents

Respiratory System Agents

Oxycodone

Escitalopram

Ondansetron

Norepinephrine

Citalopram

Analgesics, Opioid

Tramadol

Antidepressive Agents

Selective Serotonin Reuptake Inhibitors

Dexetimide

Venlafaxine Hydrochloride

Desvenlafaxine Succinate

Hydrocodone

Serotonin

Codeine

Patients who have been prescribed either 1) the selective serotonin reuptake inhibitors (SSRI) citalopram or escitalopram, or 2) the selective norepinephrine reuptake inhibitors (SNRI) venlafaxine or desvenlafaxine

Patients who have been prescribed opioid pain medications including codeine, oxycodone, hydrocodone, or tramadol.

Patients who have been prescribed the antiemetic agent ondansetron

Evaluating potential drug interactions with CYP2D6, CYP2C9 and CYP3A4 inhibitors and inducers using the Medical Letter.

Drug-Drug interaction analysis

Richard Kim, MD

Samantha Medwid, PhD

A prospective longitudinal cohort study that will assess the effect of a Personalized Medicine (PM) clinic recommendations on pharmacogenetic variation and/or interacting drugs on plasma drug exposure, effectiveness or toxicity of commonly used antidepressant, pain, and antiemetic medications in cancer patients. Such recommendations will entail genotype-guided treatment suggestions while also considering potential DDI, and will be provided to patients during their clinic visit, and referring physicians thereafter. Drug concentration and therapeutic effectiveness will be assessed before (baseline) and 6 months after recommendations have been provided. To assess effectiveness, patient-reported outcomes will be evaluated using validated scales for symptoms of depression, pain and chemotherapy-induced nausea/ vomiting

The investigators hypothesize that the pharmacogenetic variation and DDI, if applicable, determine steady state drug concentration and therapeutic response or toxicity of the investigated antidepressant, pain or antiemetic treatments at baseline, while there is a clinically significant reduction or absence of the effect 6 months after the PM clinic recommendations to referring physicians and patients.

This prospective longitudinal study will consist of three cohorts of adult cancer patients routinely referred to the PM clinic for genotype-guided chemotherapy including 5-FU or tamoxifen that are also taking antidepressant, analgesic and/or antiemetic medications.

Patients will be assigned to one or more cohorts, as appropriate, at the screening visit: Cohort 1 (n=200) if prescribed antidepressants including the selective serotonin reuptake inhibitors (SSRI) citalopram or escitalopram, or the selective norepinephrine reuptake inhibitors (SNRI) venlafaxine or desvenlafaxine; Cohort 2 (n=200) if prescribed opioid pain medications including codeine, oxycodone, hydrocodone, or tramadol; and/or Cohort 3 (N=200) if prescribed the antiemetic agent ondansetron.

Each patient will participate in a PM clinic screening visit. Eligible patients will attend three subsequent study visits at 0.5, 4 (virtual), and 7 months after screening. At each PM clinic visit, clinical information and a venous blood sample will be collected. Patients will also complete the ESAS survey and validated scores/ surveys to evaluate treatment effectiveness.

Blood will be collected at each in-person appointment for extraction of DNA (genotype) and plasma (drug level analysis).

Implementation of Personalized Medicine for Optimal Drug Therapy in Cancer

Evaluating the Implementation of Personalized Medicine for Optimal Drug Therapy in Cancer Patients: A Prospective Longitudinal Trial

Steady-state drug plasma concentration of the antidepressant (Cohort 1), pain (Cohort 2) or antiemetic medication (Cohort 3) at follow-up visit 2 at 6 months compared to the baseline visit as assessed by single time points

Difference in ESAS survey results in each cohort at the follow up visits (3 and 6 months) compared to baseline visit

Difference in CES-D survey results in each cohort at the follow up visits (3 and 6 months) compared to baseline visit

Difference in VAS Pain score in each cohort at the follow up visits (3 and 6 months) compared to baseline visit

Difference in MAT survey results in each cohort at the follow up visits (3 and 6 months) compared to baseline visit

Difference in ASEC score in each cohort at the follow up visits (3 and 6 months) compared to baseline visit

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Effect of Gene Polymorphisms on the Pathogenesis of Cancer Cachexia	NCT04131478	Cancer Cachexia	Pharmacogenetic...	18 Years - 80 Years	Cairo University
Pharmacogenetic Determinants Of Treatment Response In Children	NCT00730678	All Malignancie... Children Being ...		-	St. Jude Children's Research Hospital
Implementation of Personalized Medicine for Optimal Drug Therapy in Cancer	NCT05830279	Nausea With Vom... Depression, Rea... Cancer Pain	Pharmacogenetic... Drug-Drug inter...	18 Years -	Lawson Health Research Institute

Spots Global Cancer Trial Database for pharmacogenetic testing