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Chronic Administration of Opioids in Cancer Chronic Pain:an Open Prospective Study on Efficacy, Safety and Pharmacogenetic Factors Influence.

Phase 4
18 Years
Open (Enrolling)
Chronic Pain

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Trial Information

Chronic Administration of Opioids in Cancer Chronic Pain:an Open Prospective Study on Efficacy, Safety and Pharmacogenetic Factors Influence.

Pain continues to be a major problem in patients with cancer, affecting 25% to 30% of
patients with recently diagnosed cancers. The incidence of pain in advanced stages of cancer
approaches 70% to 80%. There are a number of reasons that patients with cancer experience
chronic pain either related to the disease itself or to its treatment.

Cancer can spread by metastasis or direct invasion, and 90% of patients with metastasis to
osseous structures report pain. Patients with cancer can have neuropathic pain due to direct
compression of nerves or plexus or spinal cord involvement.

Inadequate treatment and undertreatment are associated with increased pain scores, decreased
functional ability, and increased depression and anxiety.

Opioid administration though proven to be effective still meets with resistance from both
healthcare operators, who are seldom willing to prescribe these drugs, and patients, who
tend to not take them because of many false beliefs still related to opioids.

It is well demonstrated by the literature that opioids are effective in controlling both
acute and chronic pain of nociceptive and/or neuropathic origin. Switching type of opioid
and/or administration routes (e.g., from oral to neuraxial) is also known to be an important
factor in long-term treatment: appropriate conversion tables elucidating drug equipotence
and different potency in base of administration route for the different opioids currently
available have therefore been devised and validated in the clinical setting.

There have been several attempts to define guidelines for treatment protocols and even
recent meta-analyses indicate that morphine should remain the gold standard. However, a
general consensus is still lacking, as opioid management depends not only on the type and
cause of pain, but also on the patient's history, the pain characteristics and genetic
patterns. Which, if any, is the best opioid, in relation with previous characters, to start
systemic treatment remains therefore debated. The different effects that different opioids
have on spinal cord sensitization as a result of continuous peripheral nociceptive stimulus
in long term administration have also been partially investigated.

Current pharmacogenetic publications analyze the pharmacokinetic behavior of opioids in
short-term administration, but studies are still lacking on how the pharmacokinetics and
analgesic effect vary after repeated administrations of opioids, especially through direct
comparison with clinical response. Genetic studies showed differences in the results of
opioid treatment related to the variability of the genes that have a role in the
pharmacodynamic and pharmacokinetics of opioids. Regardless these studies, the literature
has not yet investigated how quantitative and qualitative variability of gene products can
influence the efficacy or the toxicity of a specific opioid treatment.

Inclusion Criteria:

- Adult oncologic patients (>= 18 years old)

- Chronic peripheral neuropathic and/or nociceptive pain

- Written informed consent

Exclusion Criteria:

- Pediatric patients

- Mental impaired patients

- Substance abuse disorder

- Opioid allergy

- History of opioids use or addiction

- Severe immunodeficiency, severe renal impairment, severe liver disease

- Cachectic state

- HIV positive patients

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Treatment

Outcome Measure:

To identify the drug with the best clinical-pharmacological safety-efficacy profile among the four opioids: oral extended-release morphine, oral extended-release oxycodone, transdermal fentanyl and transdermal buprenorphine.

Outcome Description:

We will define a treatment effective if it will produce a mean reduction of NRS values at least of 40% than basal values. Among all effective treatments, we will identify the best as the one that will have a reduction of NRS to a value of 4 or less in 90% of patients compared to the 70% of the others treatments. To evaluate pharmacological safety the plasma concentrations of the drugs and their metabolites will be measured. We will branch patients population in 3 groups to evaluate the correlation between clinical-pharmacological response and genetics (responder,partially and not responder)

Outcome Time Frame:

15 days after randomization (Reduction of at least 40% of median daily pain, on a NRS)

Safety Issue:


Principal Investigator

Massimo Allegri, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

IRCCS Foundation Policlinico "San Matteo", Pavia, Italy


Italy: The Italian Medicines Agency

Study ID:




Start Date:

February 2009

Completion Date:

December 2015

Related Keywords:

  • Chronic Pain
  • Opioid pharmacogenetics
  • Opioid pharmacokinetic
  • Long-term opioid treatment
  • Cancer pain