Use this URL to cite or link to this record in EThOS:
Title: Optimising opioids for cancer pain : investigating the basis of inter-individual analgesic response and side-effect profile
Author: Droney, Joanne
ISNI:       0000 0004 2716 8858
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2012
Availability of Full Text:
Access from EThOS:
Access from Institution:
There is significant inter-individual variation in response to morphine in terms of analgesia and side-effects. In recent years there has been growing interest in the possibility that genetic factors may play a role in variability in morphine response. The aims of this thesis were to develop a clinically relevant method of defining response to morphine, to investigate how multiple clinical and genetic factors may interact together to influence response to morphine and to explore constipation as a common side-effect of morphine. Clinical and biological data were collected as part of two clinical trials: 1) A prospective observational study which included patients taking oral morphine for cancer pain (N=298) and 2) A prospective follow-up randomised controlled trial of oral morphine versus oral oxycodone for cancer pain (recruitment ongoing). Symptom complexes were examined using Principal Components Analysis. Genetic association testing was carried out using both the candidate gene approach (sequence-specific primers with polymerase chain reaction) and genome-wide assays. Multivariate regression analyses were used to explore gene-gene and gene-environment interactions. Preliminary testing of a constipation assessment tool was performed. Analgesic response and central side-effects appear to be distinct components of morphine response. The genetic and clinical factors associated with these clinical outcomes and with daily morphine dose requirements are markedly different. There is inter-individual variation in bowel function in cancer patients on oral morphine. Constipation is a common symptom and is generally poorly managed. It is too early to be able to apply the results of genetic association studies of morphine response in cancer pain to clinical practice. Response to morphine is complex, both in terms of clinical confounders and pharmacogenetics. Challenges for future research include carrying out carefully designed studies of adequate power, standardising outcome measures of response to morphine and expansion of the genetic association testing.
Supervisor: Not available Sponsor: Royal Marsden Charitable Fund ; Royal Marsden Palliative Care Research Fund ; Asmarley Trust
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral