Precision Medicine Guided Treatment for Cancer Pain

Summary

Pain is one of the most burdensome symptoms associated with cancer and its treatment, and opioids are the cornerstone of clinical pain management in cancer patients. Yet, individual patient responses to opioids vary widely, and the patient's genotype contributes to this variability. Specifically, cytochrome P450 2D6 (CYP2D6) genotype has important relevance for response to opioid analgesics that depend on CYP2D6 for bioactivation. Poor metabolizers (PMs) have lower concentrations of active metabolites of codeine (morphine), tramadol (O-desmethyltramadol), oxycodone (oxymorphone), and hydrocodone (hydromorphone), compared to extensive metabolizers (EMs). Morphine and O-desmethyltramadol have 200-fold greater affinity for the µ-opioid receptor than the parent compound, whereas oxymorphone and hydromorphone have 40-fold and 10-fold higher receptor affinity compared to their parent compounds, respectively. Consequently, PMs may fail to derive pain relief from these opioids compared to EMs. Interestingly, the occurrence of side effects may not differ between PMs and EMs so that while PMs may get little to no pain relief from certain opioid analgesics, they may still experience troublesome adverse effects. Intermediate metabolizers (IMs) are also expected to have reduced analgesic response based on their significant reduction in enzyme activity. Conversely, individuals with the UM phenotype may have toxic concentrations of active opioid metabolites, with reports of life-threatening toxicity and death. The µ-opioid receptor gene (OPRM1) is the primary binding site for endogenous opioid peptides and opioid analgesics, and may have additional contributions to opioid response. The investigators propose to examine the effect of CYP2D6 genotype-guided pain management on cancer pain control in study participants and the additional effect of the OPRM1 genotype on response to opioids.

Conditions

• Pain
• CYP2D6 Polymorphism

Interventions

GENETIC

CYP2D6

Gentic testing for CYP2D6 metabolic pathway will be performed at baseline.

BEHAVIORAL

Brief Pain Inventory-Short Form (BPI-SF)

This questionnaire will be completed at baseline and weeks 2, 4, 6 and 8.

BEHAVIORAL

M.D. Anderson Symptom Inventory (MDASI)

This questionnaire will be completed at baseline and weeks 2, 4, 6 and 8.

GENETIC

OPRM1

Genetic testing of the OPRM1 will be performed after week 8.

Sponsors & Collaborators

• University of Florida

  lead OTHER

Principal Investigators

• Larisa H Cavallari, PharmD · University of Florida

Study Design

Allocation

RANDOMIZED

Purpose

SUPPORTIVE_CARE

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

120 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2016-04-30

Primary Completion

2019-01-10

Completion

2019-01-10

Countries

• United States

Study Locations