Genetic variation and cognitive dysfunction in opioid-treated patients with cancer

Psychostimulants have been used to treat many symptoms associated with advanced cancer. The primary role of psychostimulants in such cases is the treatment of symptoms such as cancer-related fatigue, opioid-induced sedation, depression, and cognitive dysfunction associated with malignancies. These uses for psychostimulants came after approval for treatment of disorders such as attention deficit disorder. Modafinil, a new psychostimulant, is following a similar path after its approval for use in attention deficit disorder in 1998. Modafinil has been used to treat fatigue associated with neurodegenerative disorders such as multiple sclerosis and amyotrophic lateral sclerosis. It is now being increasingly used for cancerrelated symptoms targeted by psychostimulants. Preliminary evidence from literature review suggests that modafinil is efficacious in improving opioid-induced sedation, cancer-related fatigue, and depression. There is no evidence to support its use in the treatment of cognitive dysfunction related to cancer or to support its having analgesic properties. Well-designed, randomized, controlled clinical trials are still needed to further elucidate the precise role of this drug in the care of patients with cancer. Specifically, large placebo-controlled trials with modafinil must be conducted in patients with cancer, with specific attention paid to pain control, depression, cognitive function, and adverse effects.

Download Full-text

The panorama of opioid-related cognitive dysfunction in patients with cancer

Cancer ◽

10.1002/cncr.10389 ◽

2002 ◽

Vol 94 (6) ◽

pp. 1836-1853 ◽

Cited By ~ 76

Author(s):

Peter G. Lawlor

Keyword(s):

Cognitive Dysfunction ◽

Patients With Cancer

Download Full-text

All You Need to Know About DPYD Genetic Testing for Patients Treated With Fluorouracil and Capecitabine: A Practitioner-Friendly Guide

JCO Oncology Practice ◽

10.1200/op.20.00553 ◽

2020 ◽

Vol 16 (12) ◽

pp. 793-798

Author(s):

Federico Innocenti ◽

Sarah C. Mills ◽

Hanna Sanoff ◽

Joseph Ciccolini ◽

Heinz-Josef Lenz ◽

...

Keyword(s):

Genetic Variation ◽

Genetic Testing ◽

Health Care Professionals ◽

Genetic Variants ◽

Drug Exposure ◽

The United States ◽

Informed Decision ◽

Dpyd Gene ◽

Patients With Cancer ◽

Increased Risk

Fluoropyrimidines (fluorouracil, capecitabine, and other analogs) are highly used anticancer drugs worldwide. However, patients with cancer treated with these drugs might experience severe, life-threatening toxicity because of germline genetic variation in the DPYD gene. This is a genetic predisposition with an established mechanistic basis that links genetic variation in the DPYD gene to an increase in systemic drug exposure, resulting in an increased risk of toxicity. Pharmacology guidelines provide recommendations on avoiding treatment with fluoropyrimidines or reducing their dose in patients carrying DPYD genetic variants conferring an increased risk of toxicity. However, oncology societies in the United States do not recommend systematic testing. Instead, on April 30, 2020, the European Society for Medical Oncology issued a document recommending genetic testing. In this scenario of contradicting information, practicing oncologists struggle with reaching an informed decision on whether genetic testing should be applied before treatment. This is mostly due to uncertainty about the clinical relevance of genetic testing from the perspective of a practicing oncologist. To reach an informed decision, practicing oncologists need access to concise information on the genetic variants to be tested and a practitioner-friendly interpretation of the test results. We believe this information is currently lacking. To our knowledge, for the first time, we provide a single guide for health care professionals to make an evidence-based decision about DPYD testing for patients with cancer. This article provides the essential knowledge base for oncologists to have an informed discussion with their patients about the genetic testing for DPYD. This document assists practitioners in quickly evaluating whether, when, where, and how to order a DPYD genetic test.

Download Full-text

Cognitive Functions in Patients with Brain Tumors

The Oxford Handbook of Adult Cognitive Disorders ◽

10.1093/oxfordhb/9780190664121.013.20 ◽

2019 ◽

pp. 425-449

Author(s):

Denise D. Correa

Keyword(s):

Brain Tumors ◽

Cognitive Dysfunction ◽

Multicenter Studies ◽

Treatment Interventions ◽

Patients With Cancer ◽

Oncology Research ◽

New Information ◽

The Central Nervous System ◽

Underlying Mechanisms ◽

Methods Of Treatment

Patients with cancer of the central nervous system often experience cognitive dysfunction as a result of the tumor and its treatment, including radiotherapy and chemotherapy. Difficulties in aspects of attention and executive functions, and learning and retrieval of new information, are the most prevalent in survivors, and they often interfere with survivors’ ability to resume work and social activities. As effective treatment interventions have increased survival, there has been growing recognition of the relevance of including cognitive evaluations as outcome variables in neuro-oncology research. Advancements in the field include the development of guidelines for the use of standardized neuropsychological instruments in the context of clinical trials and the inclusion of sensitive cognitive tests in several multicenter studies. Recent studies have also begun to investigate the underlying mechanisms and genetic risk factors that may contribute to treatment neurotoxicity. This chapter reviews the literature on cognitive dysfunction in patients with brain tumors, mechanisms of neurotoxicity, and currently used methods of treatment and management.

Download Full-text

Prevalence and Predictors of Cognitive Dysfunction in Opioid-Treated Patients With Cancer: A Multinational Study

Journal of Clinical Oncology ◽

10.1200/jco.2010.32.6884 ◽

2011 ◽

Vol 29 (10) ◽

pp. 1297-1303 ◽

Cited By ~ 53

Author(s):

Geana P. Kurita ◽

Per Sjøgren ◽

Ola Ekholm ◽

Stein Kaasa ◽

Jon H. Loge ◽

...

Keyword(s):

Lung Cancer ◽

Cognitive Dysfunction ◽

Breakthrough Pain ◽

Karnofsky Performance Status ◽

Performance Status ◽

Oral Morphine ◽

Older Age ◽

Cross Sectional ◽

Logistic Regression Models ◽

Patients With Cancer

Purpose To identify prevalence and associated factors of cognitive dysfunction in opioid-treated patients with cancer. Patients and Methods EPOS (European Pharmacogenetic Opioid Study) is a prospective cross-sectional multicenter study in which adult patients with cancer who received treatment with opioids for moderate or severe pain for at least 3 days were included. Cognitive function was assessed using the Mini-Mental State Examination (MMSE). MMSE scores were categorized into definite cognitive dysfunction (scores < 24), possible cognitive dysfunction (scores 24-26), and no cognitive dysfunction (scores > 26). Factors potentially associated with cognitive dysfunction were assessed. Associations between MMSE and explanatory variables were analyzed by ordinal logistic regression models. Results We included 1,915 patients with cancer from 17 centers. MMSE scores less than 27 were observed in 32.9% of patients. Patients with lung cancer had higher odds (adjusted odds ratio, 1.46; 95% CI, 1.09 to 1.95) for having lower MMSE scores compared with patients with other cancer diagnoses. Patients receiving daily opioid doses of 400 mg or more (oral morphine equivalents) had 1.75 (95% CI, 1.25 to 2.46) times higher odds of having lower MMSE scores compared with those receiving daily doses less than 80 mg. Other risk factors for cognitive dysfunction were older age, low Karnofsky performance status (KPS), time since diagnosis (< 15 months), and absence of breakthrough pain (BTP). Conclusion One third of opioid-treated patients with cancer had possible or definite cognitive dysfunction. Lung cancer, daily opioid doses of 400 mg or more (oral morphine equivalents), older age, low KPS, shorter time since cancer diagnosis, and absence of BTP were predictors for cognitive dysfunction.

Download Full-text