The long and winding road of non steroidal antinflammatory drugs and paracetamol in cancer pain management: A critical review

Abstract

The aim of this review was to assess the value of NSAIDs and paracetamol in patients with cancer pain to update a previous review performed ten years ago on this topic. The approach was analytic and based on clinical considerations, rather than on raw evidence, which often does not provide useful information in clinical practice. Both published reports from an extensive search of electronic data bases were collected from January 2001 to December 2011. A free-text search method was used including the following words and their combination: "Anti-inflammatory drugs OR paracetamol OR acetaminophen" AND/OR "cancer pain". Any randomized-controlled trial was considered. Thirteen reports fulfitted inclusion criteria in this systematic review. Randomized trials have been performed by using different modalities of intervention. Single drugs added on opioid therapy or during opioid substitution with opioids as rescue drugs through a patient controlled analgesia, were compared with placebo or between them. Five studies regarded paracetamol. Other four studies assessed the efficacy dipyrone, ketorolac, dexketoprofen, and subcutaneous ketoprofen in cancer pain management, mainly on top of an opioid regimen. The role of paracetamol and NSAIDs in the management of cancer pain still remains controversial. The papers published in this last decade were unable to answer the main questions. There is no proof that they should be used to start the treatment and how long they should be administered when opioid treatment is added on top. While paracetamol seems to be devoid of any benefit, particularly if given at usual clinical doses which should be less than 4 g/day, ketorolac seems to provide an additive analgesic effect even in patients receiving different doses of opioids. The main indication from the analysis of these data is that NSAIDs could be given in patients receiving opioids, evaluating their benefit and weight on opioid therapy in individual patients who have a favorable response to justify a prolonged use.

Behavioral and neurochemical analysis of ongoing bone cancer pain in rats

“…1 The rationale for continuing NSAID treatment in addition to opioids is to improve analgesic efficacy while minimizing the potential for aversive effects witnessed by opioid treatments alone, that is, producing opioid-sparing effects. 35 However, continuation of NSAIDs with opioids is controversial because of the development of side effects to the NSAIDs and limited evaluation of whether patients receive improved pain relief with the coadministration of NSAIDs with opioids. 32 , 35 Our data demonstrate that acute diclofenac administration at a dose that blocks tumor-induced tactile hypersensitivity failed to induce CPP or DA release within the NAc shell, suggesting that it is not effective in alleviating the tumor-induced ongoing bone pain in this model at the time point tested.…”

“… 5 , 11 , 43 Moreover, opioid doses required for these patients are associated with adverse side effects further diminishing quality of life. 32 , 35 , 36 , 40 , 46 Development of improved nonopioid therapies is dependent on increased understanding of mechanisms driving cancer pain and its relief.…”

Opioids in treatment of cancer pain

“…Примена неопиоидних ана л гетика у комбинацији са опиоидима одлаже развој толеранције, што омогућава употребу мањих доза опијата чиме се смањују њихова нежељена дејства. (1,6) Ацетаминофен (парацетамол) је нео пиои дни аналгетик са мање нежељених ефе ката у односу на НСАИЛ. Механизам дејства парацетамола још увек није довољно познат.…”

Mechanism-based cancer-pain therapy

“…For example, systematic reviews of basic analgesics suggest that paracetamol is likely to be ineffective, particularly in patients already treated with strong opioids, whereas there are no good quality studies of non-steroidal anti-inflammatory drugs (NSAIDs) to guide practice [33,34]. Strong opioids are generally effective with about 75% of patients achieving satisfactory pain control after first or second line opioid treatment, with no significant differences in efficacy between morphine, oxycodone, fentanyl or buprenorphine [10,41,42,52].…”