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Written by

Professor Alain Borgeat Professor Alain Borgeat is head, department of anaesthesiology, Uniklinik Balgrist, Zurich, Switzerland

Dr Jan H Vranken Dr Jan H Vranken is an anaesthesiologist – pain specialist at Slotervaartziekenhuis and Medical Centre Jan van Goyen, Amsterdam, The Netherlands

Dr Simon Wein Dr Simon Wein is from the Pain and Palliative Care Service, Davidoff Center, Rabin Medical Center, Petach Tikvah, Israel

Combined oxycodone/naloxone for pancreatic cancer pain

Published 31 July 2015

Professor Alain Borgeat presents a case of severe lower thoracic chronic pain due to advanced pancreatic cancer

Key learning points

  • Chronic thoracic back pain may be a presenting symptom of pancreatic cancer.
  • Pancreatic cancer pain tends to be a mix of neuropathic and nociceptive components, and therefore different analgesics are usually necessary.
  • Opioids are still the cornerstone analgesic therapy for this condition.
  • The choice of opioid should be tailored to each patient.
  • The level of anxiety and depression is very high in pancreatic cancer.

Background

Pancreatic cancer pain may be severe and includes both neuropathic and nociceptive components. The pain is often exacerbated by surgery or radiation and chemotherapy. These factors make the management of this condition a real challenge, which is complicated by the high level of anxiety and depression associated with the poor prognosis of this disease.1

 

Case assessment

A 62-year-woman was admitted with low thoracic dorsal pain.
This condition was known for more than 10 years, but recently the intensity of the pain increased significantly, necessitating treatment with paracetamol, diclofenac and tramadol. Within the previous two weeks the pain had become worse and nocturnal, waking the patient several times. The patient complained of increasing fatigue, loss of appetite and weight loss. On physical examination, T10–12 of the thoracic vertebra were tender to palpation. The abdomen was distended and rigid. Her liver function tests, lipase, and amylase were elevated. A complete CT scan of the abdomen revealed an enlarged body of the pancreas (Figure 1). A total pancreatectomy was performed. Postoperatively, the patient received adjuvant radiotherapy. At the end of this therapy, the patient complained of severe pain rated 8 on the visual analogue scale (VAS; from 0 = no pain to 10 = worst pain imaginable). The pain was constant and consisted of a mix of neuropathic and nociceptive components. Treatment with pregabalin 50mg (titrated up to 200mg/daily), celecoxib (2 x 200mg), Paracetamol (4 x 1g) and prolonged release oral oxycodone (2 x 20mg) was started. Duloxetine 60mg once daily was added after a consultant psychiatrist diagnosed a high level of anxiety and depression. 

 

pancreatic-cancer

Figure 1. CT scan showing enlarged body of the pancreas

Under this regimen the pain intensity decreased steadily to 2 on the VAS one month later. However, severe painful constipation due to episodes of abdominal cramping occurred, which was resistant to laxatives (lactulose) and prokinetic medications (metoclopramide). Therefore, the pain increased to 5 on the VAS. At this time, oxycodone was switched to a combined preparation of prolonged release oral oxycodone 40mg and naloxone 20mg (Targin®*) twice daily, and macrogol was prescribed as required, up to two doses per day. The situation improved rapidly, and after one week the patient had complete bowel movements two times a week. After three weeks, complete bowel movements occurred three times a week. At this stage, the cramping abdominal pain disappeared and the VAS returned to 2. This situation remained stable for the next six months. At this time, the patient suddenly suffered from a severe attack of abdominal pain, was hospitalised, and had died within 12 hours. 

 

Discussion

Pain is the most common presenting symptom in patients with pancreatic cancer. Usually, the pain takes the form of mild to moderate mid-epigastric tenderness2 However, in some cases (as in this case) the pain occurs in the mid- or lower back. Such occurrence is worrisome, as it indicates retroperitoneal invasion of the splanchnic nerve plexus by the tumour. Therefore, the pain may become very severe since a mix of neuropathic and nociceptive pain will occur simultaneously. This necessitates the introduction of different drugs to manage all the pain components. Finally, the pain may be further exacerbated by radiation and chemotherapy. Psychological factors also play a major role in the exacerbation of the pain.3 The place of opioids is fundamental, and correct selection, as illustrated in this case, is crucial to avoid new bothersome and painful side-effects. 

  • Professor Alain Borgeat is head of the department of anaesthesiology, Balgrist University Hospital, Zurich, Switzerland 

This case report illustrates what could be achieved with oxycodone/naloxone prolonged release tablets, rather than what should routinely be expected

*Targin® (oxycodone/naloxone) is licensed for severe pain which can be adequately managed only with opioid analgesics. Targin® is also known as Targinact® and Targiniq® in other countries. UK prescribing information can be found via link below.

References

  1. Turaga KK, Malafa MP,  et al. Cancer 2011;117(3):642–647.
  2. Spiro HM. Clinical enterology. 4th ed. New York: McGraw-Hill, 1993; pp1028–1033.
  3. Gehdoo RP. Indian Journal of Anaesthesiology 2006;50(5):375–390.

Case review: The Netherlands

Dr Jan H Vranken

Anaesthesiologist – pain specialist, Nij Smellinghe Hospital, Drachten and Medical Centre Jan van Goyen, Amsterdam, The Netherlands 


In a recent review, opioids alleviated nociceptive and neuropathic pain with a mean decrease in pain intensity of at least 30%.1 Opioids do not always provide sufficient pain relief and adverse effects, tolerance and addiction can compromise the outcome. In addition, 80% of patients experience at least one side-effect.1 The gastrointestinal tract is a significant site of opioid-related adverse effects due to the presence of opioid receptors, whose activation by exogenous opioids inhibits normal bowel function. Side-effects include decreased gastric emptying, abdominal cramping, spasm, bloating and hard dry stools. Constipation, the most common side-effect, is an almost inevitable consequence of long-term opioid use, such as in advanced cancer (occurring in around 80% of patients2). It is persistent and may limit therapy, worsen analgesia and compromise quality of life. Because there is no evidence that tolerance develops to constipation, opioid rotation to an opioid with a lower constipation-inducing potential compared with morphine (such as transdermal fentanyl)3 or treatments that block peripheral opioid receptors in the gut without reversing a centrally-mediated effect of opioids, such as analgesia, would be valuable alternative strategies.

In this patient, a combination of prolonged oxycodone/naloxone, with macrogol as needed, gave adequate pain relief with manageable side-effects. The advantage of this compound is less constipation for a given degree of analgesia.4 This opioid, with a favourable dose to constipation ratio, may be preferred by patients and can be titrated at higher dosages with the potential for better pain control, as in this case.

References 

  1. Kalso E, Edwards JE, Moore RA, et al. Pain 2004;112(3):372–380.
  2. Bell TJ, Panchal SJ, et al. Pain Medicine 2009;10(1):35–42.
  3. Clark AJ, Ahmedzai SH, et al. Current Medical Research and Opinion 2004;20(9):1419–1428.
  4. Ahmedzai SH, Leppert W, et al. Supportive Care in Cancer 2015;23(3):823–830.

Case review: Israel

Dr Simon Wein

Pain and Palliative Care Service, Davidoff Center, Rabin Medical Center, Petach Tikvah, Israel


The classic presentation of pancreatic cancer illustrates the triad of jaundice, weight loss and pain. The site and radiation of the pain depends on whether the tumour is in the head, body or tail of the pancreas. In this case the tumour was in the body, which commonly causes deep upper-abdominal pain that radiates to the back, and can mimic non-specific lower thoracic pain. 

Patients typically do not describe allodynia, burning, electric shocks or pins and needles, so the neuropathic element of pancreatic cancer pain is presumptive. Nevertheless, the pain responds to anti-neuropathic agents. Pregabalin is a reasonable first choice followed by gabapentin and/or amitriptyline. Success is also possible with methadone (with its N-methyl-D-aspartate receptor activity) rather than combining other opioids with anti-neuropathic agents.

Traditionally, depression was thought to be more common in patients with pancreatic cancer than other cancers, possibly due to hormonal influences. This is unproven and it is more likely that the severity of pain causes emotional distress. Interestingly, duloxetine (a serotonin-noradrenaline reuptake inhibitor [SNRI]) was chosen to manage the depression. This drug is also used for treating neuropathic pain, as is another SNRI, venlafaxine (unlicensed usage). Caution should be exercised with the 4g daily dosage of paracetamol being used, as this may be too much in the long term. 

Constipation, the scourge of opioid prescribing, has been shown to improve with use of the combined oxycodone/naloxone tablet.1 Pain control in patients with cancer requires close attention to opioid side-effects. 

References 

  1. Ahmedzai SH, Leppert W, et al. Supportive Care in Cancer 2015;23(3):823–830.

Date of preparation: July 2015. Item code: MINT/PAEU-15001u