An overview of the current drug treatment strategies for moderate to severe, chronic malignant tumor-related pain

References

• Treede RD, Rief W, Barke A, et al. “A classification of chronic pain for ICD-11. Pain. 2005;156(6):1003. DOI:10.1097/j.pain.0000000000000160
   Google Scholar
• Breivik H, Cherny N, Collett B, et al. Cancer-related pain: a pan-European survey of prevalence, treatment, and patient attitudes. Ann Oncol. 2009;20(8):1420–1433. DOI:10.1093/annonc/mdp001
   PubMed Web of Science ®Google Scholar
• van den Beuken-van Everdingen MH, Hochstenbach LM, Joosten EA, et al. Update on prevalence of pain in patients with cancer: systematic review and meta-analysis. J Pain Symptom Manag. 2016;51(6):1070–1090.
   PubMed Web of Science ®Google Scholar
• Knudsen AK, Brunelli C, Kaasa S, et al. Which variables are associated with pain intensity and treatment response in advanced cancer patients?–implications for a future classification system for cancer pain. Eur J Pain. 2011;15(3):320–327. DOI:10.1016/j.ejpain.2010.08.001
   PubMed Web of Science ®Google Scholar
• Makhlouf SM, Pini S, Ahmed S, et al. Managing pain in people with cancer—a systematic review of the attitudes and knowledge of professionals, patients, caregivers and public. J Cancer Educ. 2020;35(2):214–240.
   PubMed Web of Science ®Google Scholar
• Fallon M, Giusti R, Aielli F, et al. Management of cancer pain in adult patients: eSMO clinical practice guidelines. ESMO Guidelines Committee Ann Oncol. 2018;29(Suppl 4):iv166–191. DOI:10.1093/annonc/mdy152
   PubMed Web of Science ®Google Scholar
• Koyyalagunta D, Bruera E, Solanki D, et al. A systematic review of randomized trials on the effectiveness of opioids for cancer pain. Pain Physician. 2012;15:ES39–58.
   PubMed Web of Science ®Google Scholar
• Caraceni A, Hanks G, Kaasa S, et al. Use of opioid analgesics in the treatment of cancer pain: evidence-based recommendations from the EAPC. Lancet Oncol. 2012;13(2):e58–68. DOI:10.1016/S1470-2045(12)70040-2
   PubMed Web of Science ®Google Scholar
• Mercadante S. Opioid titration in cancer pain: a critical review. Eur J Pain. 2007;11(8):823–830.
   PubMed Web of Science ®Google Scholar
• Mercadante S, Porzio G, Ferrera P, et al. Low morphine doses in opioid-naive cancer patients with pain. J Pain Sympt Manage. 2006;31(3):242–247. DOI:10.1016/j.jpainsymman.2006.01.001
   PubMed Web of Science ®Google Scholar
• Bandieri E, Romero M, Ripamonti CI, et al. Randomized trial of low-dose morphine versus weak opioids in moderate cancer pain. J Clin Oncol. 2016;34(5):436. DOI:10.1200/JCO.2015.61.0733
   PubMed Web of Science ®Google Scholar
• Zheng RJ, Fu Y, Zhu J, et al. Long-term low-dose morphine for patients with moderate cancer pain is predominant factor affecting clinically meaningful pain reduction. Support Care Cancer. 2018;26(12):4115–4120. DOI:10.1007/s00520-018-4282-2
   PubMed Web of Science ®Google Scholar
• Mercadante S, Porzio G, Ferrera P, et al. Low doses of transdermal buprenorphine in opioid-naive patients with cancer pain: a 4-week, nonrandomized, open-label, uncontrolled observational study. Clin Ther. 2009;31(10):2134–2138. DOI:10.1016/j.clinthera.2009.10.013
   PubMed Web of Science ®Google Scholar
• Mercadante S, Porzio G, Ferrera P, et al. Low doses of transdermal fentanyl in opioid-naive patients with cancer pain. Curr Med Res Opin. 2010;26(12):2765–2768. DOI:10.1185/03007995.2010.532545
   PubMed Web of Science ®Google Scholar
• Mercadante S, Adile C, Ferrera P. Methadone as first-line opioid for the management of cancer pain. Oncology. 2022;27(4):323–327.
   Google Scholar
• Mercadante S. Opioid metabolism and clinical aspects. Eur J Pharmacol. 2015;769:71–78.
   PubMed Web of Science ®Google Scholar
• Klepstad P, Kaasa S, Borchgrevink PC. Starting step III opioids for moderate to severe pain in cancer patients: dose titration: a systematic review. Palliat Med. 2011;25(5):424–430.
   PubMed Web of Science ®Google Scholar
• Mercadante S. Intravenous morphine for management of cancer pain. Lancet Oncol. 2010;11(5):484–489.
   PubMed Web of Science ®Google Scholar
• Takahashi M, Ohara T, Yamanaka H, et al. The oral-to-intravenous equianalgesic ratio of morphine based on plasma concentrations of morphine and metabolites in advanced cancer patients receiving chronic morphine treatment. Palliat Med. 2003;17(8):673–678.
   PubMed Web of Science ®Google Scholar
• Mercadante S, Adile C, Ferrera P, et al. Rapid titration with intravenous oxycodone for severe cancer pain and oral conversion ratio. J Pain Symptom Manage. 2022;64(6):532–536.
   PubMed Web of Science ®Google Scholar
• Paice JA, Ferrell B. The management of cancer pain. CA Cancer J Clin. 2011;61(3):157–182.
   PubMed Web of Science ®Google Scholar
• Mercadante S, Arcuri E. Santoni a opioid-induced tolerance and hyperalgesia. CNS Drugs. 2019;33:943–955.
   PubMed Web of Science ®Google Scholar
• Ballantyne JC, Kalso E, Stannard C. WHO analgesic ladder: a good concept gone astray. BMJ. 2016;352:i209.
   Google Scholar
• Guichard L, Hirve A, Demiri M, et al. Opioid-induced hyperalgesia in patients with chronic pain: a systematic review of published cases. Clin J Pain. 2021;38:49–57.
   PubMed Web of Science ®Google Scholar
• Mercadante S, Portenoy RK. Opioid poorly-responsive cancer pain. 480 Part 1: clinical considerations. J Pain Symptom Manag. 2001;21(2):144–150. DOI:10.1016/S0885-3924(00)00228-1.
   PubMed Web of Science ®Google Scholar
• Fainsinger R, Nekolaichuk C, Lawlor P, et al. A multicenter study of the revised Edmonton staging system for classifying cancer pain in advanced cancer patients. J Pain Symptom Manag. 2005;29(3):224–237. DOI:10.1016/j.jpainsymman.2004.05.008
   PubMed Web of Science ®Google Scholar
• Fainsinger RL, Nekolaichuk C, Lawlor P, et al. An international muticentre validation study of a pain classification system for cancer patients. Eur J Cancer. 2010;46(16):2896–2904. DOI:10.1016/j.ejca.2010.04.017
   PubMedGoogle Scholar
• Knudsen AK, Brunelli C, Klepstad P, et al. Which domains should be included in a cancer pain classification system? Pain. 2012;153(3):696–703. DOI:10.1016/j.pain.2011.12.005
   PubMed Web of Science ®Google Scholar
• Oosten AW, Matic M, van Schaik RH, et al. Opioid treatment failure in cancer patients: the role of clinical and genetic factors. Pharmacogenomics. 2016;17:1391–1403.
   PubMed Web of Science ®Google Scholar
• Mercadante S, Villari P, Ferrera P, et al. Addition of a second opioid may improve opioid response in cancer pain: preliminary data support care cancer. Support Cancer Ther. 2004;12(11):762–766.
   Web of Science ®Google Scholar
• Courtemanche F, Dao D, Gagné F, et al. Néron a methadone as a coanalgesic for palliative care cancer. Patients J Palliat Med. 2016 Sep;19(9):972–978.
   PubMed Web of Science ®Google Scholar
• Wallace E, Ridley J, Bryson J, et al. Addition of methadone to another opioid in the management of moderate to severe cancer pain: a case series. J Palliat Med. 2013;16(3):305–309.
   PubMed Web of Science ®Google Scholar
• Fürst P. The use of low-dose methadone as add-on to ongoing opioid treatment in palliative cancer care—an underrated treatment? Life. 2022;12(5):679.
   PubMedGoogle Scholar
• Kim HJ, Kim YS, Park SH. Park SH.Opioid rotation versus combination for cancer patients with chronic uncontrolled pain: a randomized study BMC Palliat Care. BMC Palliat Care. 2015;14(1):41.
   PubMedGoogle Scholar
• Riley J, Ross JR, Rutter D, et al. No pain relief from morphine? Individual variation in sensitivity to morphine and the need to switch to an alternative opioid in cancer patients. Support Care Cancer. 2006;14(1):56–64. DOI:10.1007/s00520-005-0843-2
   PubMed Web of Science ®Google Scholar
• Cherny N, Ripamonti C, Pereira J, et al. Expert working group of the European Association of palliative care network. strategies to manage the adverse effects of oral morphine: an evidence-based report. J Clin Oncol. 2001;19(9):2542–2554. DOI:10.1200/JCO.2001.19.9.2542
   PubMed Web of Science ®Google Scholar
• Mercadante S, Bruera E Opioid switching in cancer pain: from the beginning to nowadays. Crit Rev Oncol Hematol 2016;99:241–248. DOI:10.1016/j.critrevonc.2015.12.011
   PubMed Web of Science ®Google Scholar
• Benítez-Rosario MA, Salinas-Martín A, Aguirre-Jaime A, et al. Morphine-methadone opioid rotation in cancer patients: analysis of dose ratio predicting factors. J Pain Symptom Manage. 2009;37(6):1061–1068.
   PubMed Web of Science ®Google Scholar
• Lawlor P, Turner K, Hanson J, et al. Dose ratio between morphine and methadone in patients with cancer pain. A retrospective study. Cancer 1998;82:1167–1173. DOI:10.1002/(SICI)1097-0142(19980315)82:6<1167:AID-CNCR23>3.0.CO;2-3
   PubMed Web of Science ®Google Scholar
• Pereira J, Lawlor P, Viganò A, et al. Equianalgesic dose ratios for opioids.A critical review and proposal for long-term dosing. J Pain Symptom Manage. 2001;22(2):672–687.
   PubMed Web of Science ®Google Scholar
• Quigley C Opioid switching to improve pain relief and drug tolerability. Cochrane Database Syst Rev 2004;3: CD004847.
   Google Scholar
• Morley JS, Watt JWG, Wells JC, et al. Methadone in pain uncontrolled by morphine. Lancet. 1993;342:1243.
   PubMed Web of Science ®Google Scholar
• Scholes CF, Gonty N, Trotman IF. Methadone titration in opioid-resistant cancer pain. Eur J Cancer Care. 1999;8:26–29.
   PubMed Web of Science ®Google Scholar
• Poulain P, Berleur MP, Lefki S, et al. Efficacy and safety of two methadone titration methods for the treatment of cancer-related pain: the EQUIMETH2 Trial (Methadone for Cancer-Related Pain). J Pain Symptom Manage. 2016;52(5):626–636. DOI:10.1016/j.jpainsymman.2016.05.022
   PubMed Web of Science ®Google Scholar
• Mercadante S, Casuccio A, Calderone L. Rapid switching from morphine to methadone in cancer patients with poor response to morphine. J Clin Oncol. 1999;17:3307–3312.
   PubMed Web of Science ®Google Scholar
• Mercadante S, Ferrera P, Villari P, et al. Frequency, indications, outcomes, and predictive factors of opioid switching in an acute palliative care unit. J Pain Symptom Manage. 2009;37:632–641.
   PubMed Web of Science ®Google Scholar
• Mercadante S, Giarratano A. Giarratano a the long and winding road of non steroidal anti inflammatory drugs and paracetamol in cancer pain management: a critical review.Crit. Rev Oncol Hematol. 2013;87(2):140–145.
   PubMedGoogle Scholar
• Magee DJ, Jhanji S, Poilogiannis G, et al. Nonsteroidal anti-inflammatory drugs and pain in cancer patients: a systematic review and reappraisal of the evidence.Br J Anaesth. Br J Anaesth. 2019;123(2):e412–423.
   PubMed Web of Science ®Google Scholar
• Liu M, Ma J, Li J, et al. A comparison of the clinical effectiveness between low-dose strong opioids and non-steroidal anti-inflammatory drugs in the treatment of mild cancer pain: a randomized trial. J Pain Res. 2021;14:3411–3419.
   PubMed Web of Science ®Google Scholar
• Mercadante S, Fulfaro F, Casuccio A. A randomised controlled study on the use of anti-inflammatory drugs in patients with cancer pain on morphine therapy: effects on dose-escalation and a pharmacoeconomic analysis. Eur J Cancer. 2002;38(10):1358–1363.
   PubMed Web of Science ®Google Scholar
• Nabal M, Librada S, Redondo MJ, et al. The role of paracetamol and nonsteroidal anti-inflammatory drugs in addition to WHO step iii opioids in the control of pain in advanced cancer. A systematic review of the literature Palliat med. Palliat Med. 2012;26(4):305–312. DOI:10.1177/0269216311428528
   PubMed Web of Science ®Google Scholar
• Lussier D, Huskey AG, Portenoy RK. Adjuvant analgesics in cancer pain management. Oncology. 2004;9(5):571–591.
   Google Scholar
• Jongen JL, Huijsman ML, Jessurun J, et al. The evidence for pharmacologic treatment of neuropathic cancer pain: beneficial and adverse effects. J Pain Symptom Manage. 2013;46(4):581–590. DOI:10.1016/j.jpainsymman.2012.10.230
   PubMed Web of Science ®Google Scholar
• Bennett MI. Effectiveness of antiepileptic or antidepressant drugs when added to opioids for cancer pain: systematic review. Palliat Med. 2011;25(5):553–559.
   PubMed Web of Science ®Google Scholar
• Matsuoka H, Iwase S, Miyaji T, et al. Additive duloxetine for cancer-related neuropathic pain nonresponsive or intolerant to opioid-pregabalin therapy: a randomized controlled trial (JORTC-PAL08). J Pain Symptom Manage. 2019;58(4):645–653. DOI:10.1016/j.jpainsymman.2019.06.020
   PubMed Web of Science ®Google Scholar
• Mercadante S, Arcuri E, Casuccio A. Analgesic effect of intravenous ketamine in cancer patients on morphine therapy: a randomized, controlled, double-blind, crossover, double-dose study. J Pain Symptom Manage. 2000;20(4):246–252.
   PubMed Web of Science ®Google Scholar
• Mercadante S, Villari P, Ferrera P. Burst ketamine to reverse opioid tolerance in cancer pain. J Pain Symptom Manage. 2003;25(4):302–305.
   PubMed Web of Science ®Google Scholar
• Hardy J, Quinn S, Fazekas B, et al. Randomized, double-blind, placebo-controlled study to assess the efficacy and toxicity of subcutaneous ketamine in the management of cancer pain. J Clin Oncol. 2012;30(29):3611–3617. DOI:10.1200/JCO.2012.42.1081
   PubMed Web of Science ®Google Scholar
• Mercadante S. Ketamine: to be or not to be. Ann Palliat Med. 2013;2(1):37–39.
   PubMedGoogle Scholar
• Sharma S, Rajagopal MR, Palat G, et al. A phase II pilot study to evaluate use of intravenous lidocaine for opioid-refractory pain in cancer patients. J Pain Symptom Manage. 2009;37(1):85–93. DOI:10.1016/j.jpainsymman.2007.12.023
   PubMed Web of Science ®Google Scholar
• Salas S, Auquier P, Duffaud F, et al. Efficacy of lidocaine in patients receiving palliative care with opioid-refractory cancer pain with a neuropathic component: study protocol for a randomized controlled study. Trials. 2014;15:318.
   PubMed Web of Science ®Google Scholar
• Portenoy RK, Ganae-Motan ED, Allende S, et al. Nabiximols for opioid-treated cancer patients with poorly-controlled chronic pain: a randomized, placebo-controlled, graded-dose trial. J Pain. 2012;13(5):438–449. DOI:10.1016/j.jpain.2012.01.003
   PubMed Web of Science ®Google Scholar
• Johnson JR, Lossignol D, Burnell-Nugent M, et al. An open-label extension study to investigate the long-term safety and tolerability of THC/CBD oromucosal spray and oromucosal THC spray in patients with terminal cancer-related pain refractory to strong opioid analgesics. J Pain Symptom Manage. 2013;46(2):207–218.
   PubMed Web of Science ®Google Scholar
• Lichtman AH, Lux EA, McQuade R, et al. Results of a double-blind, randomized, placebo-controlled study of nabiximols oromucosal spray as an adjunctive therapy in advanced cancer patients with chronic uncontrolled pain. J Pain Symptom Manage. 2018;55(2):179–188. DOI:10.1016/j.jpainsymman.2017.09.001
   PubMed Web of Science ®Google Scholar
• Häuser W, Petzke F, Fitzcharles MA. Efficacy, tolerability and safety of cannabis-based medicines for chronic pain management: an overview of systematic reviews. Eur J Pain. 2018;22:455–470.
   PubMed Web of Science ®Google Scholar
• Mercadante S, Portenoy RK. Breakthrough cancer pain: twenty-five years of study. Pain. 2016;157:2657–2663.
   PubMed Web of Science ®Google Scholar
• Davies A, Zeppetella G, Andersen S, et al. Multi-centre European study of breakthrough cancer pain: pain characteristics and patient perceptions of current and potential management strategies. Eur J Pain. 2011;15(7):756–763. DOI:10.1016/j.ejpain.2010.12.004
   PubMed Web of Science ®Google Scholar
• Mercadante S, Portenoy RK. Understanding the chameleonic breakthrough cancer pain. Drugs. 2021;81:411–418.
   PubMed Web of Science ®Google Scholar
• Mercadante S, Marchetti P, Cuomo A, et al. Factors influencing the clinical presentation of breakthrough pain in cancer patients. Cancers (Basel). 2018;10:175. DOI:10.3390/cancers10060175
   PubMed Web of Science ®Google Scholar
• Mercadante S. Non pharmacological interventions and non fentanyl pharmacological treatments for breakthrough cancer pain: a systematic and critical review. Crit Rev Oncol Hematol. 2018 Feb;122:60–63.
   PubMed Web of Science ®Google Scholar
• Currow DC, Clark K, Louw S, et al. A randomized, double-blind, crossover, dose ranging study to determine the optimal dose of oral opioid to treat breakthrough pain for patients with advanced cancer already established on regular opioids. Eur J Pain. 2020;24(5):983–991. DOI:10.1002/ejp.1548
   PubMed Web of Science ®Google Scholar
• Mercadante S. Pharmacotherapy for breakthrough cancer pain. Drugs. 2012;72:181–190.
   PubMed Web of Science ®Google Scholar
• Jandhyala R, Fullarton J. Various formulations of oral transmucosal fentanyl for breakthrough cancer pain: an indirect mixed treatment comparison meta-analysis. BMJ Support Palliat Care. 2012;2(2):156–162.
   PubMedGoogle Scholar
• Zeppetella G, Davies A, Eijgelshoven I, et al. A network meta-analysis of the efficacy of opioid analgesics for the management of breakthrough cancer pain episodes. J Pain Symptom Manage. 2014;47(4):772–785.
   PubMed Web of Science ®Google Scholar
• Mercadante S, Adile C, Cuomo A, et al. Fentanyl buccal tablet vs. oral morphine in doses proportional to the basal opioid regimen for the management of breakthrough cancer pain: a randomized, crossover, comparison study. J Pain Symptom Manage. 2015;50:579–586.
   PubMed Web of Science ®Google Scholar
• Mercadante S, Gatti A, Porzio G, et al. Dosing fentanyl buccal tablet for breakthrough cancer pain: dose titration versus proportional doses. Curr Opin Res Opin. 2012;28(6):963–968. DOI:10.1185/03007995.2012.683112
   PubMed Web of Science ®Google Scholar
• Davies AN, Dickman A, Reid C, et al. Science committee of the association for palliative medicine of Great Britain and Ireland.The management of cancer-related breakthrough pain: recommendations of a task group of the science committee of the association for palliative medicine of Great Britain and Ireland. Eur J Pain. 2009;13(4):331–338.
   PubMed Web of Science ®Google Scholar
• Jensen TS, Baron R, Haanpaa M, et al. A New Definition of Neuropathic Pain. Pain. 2011;152:2204–2205.
   PubMed Web of Science ®Google Scholar
• Brunelli C, Bennett MI, Kaasa S, et al. European Association for palliative care (EAPC) Research Network. Classification of Neuropathic Pain in Cancer Patients: a Delphi Expert Survey Report and EAPC/IASP Proposal of an Algorithm for Diagnostic Criteria. Pain. 2014;155:2707–2713.
   PubMed Web of Science ®Google Scholar
• van den Beuken-van Everdingen Mh, de Graeff a, Jongen JLM, et al. Pharmacological Treatment of Pain in Cancer Patients: the Role of Adjuvant Analgesics, a Systematic Review. Pain Pract. 2017;17(3):409–419. DOI:10.1111/papr.12459
   PubMed Web of Science ®Google Scholar
• Shkodra M, Caraceni A. Treatment of neuropathic pain directly due to cancer: an update. Cancer(basel). 2022;14(8):1992.
   Google Scholar
• Bechakra M, Moerdijk F, van Rosmalen J, et al. Opioid responsiveness of nociceptive versus mixed pain in clinical cancer patients. Eur J Cancer. 2018;105:79–87.
   PubMed Web of Science ®Google Scholar
• Finnerup NB, Attal N, Haroutounian S, et al. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. Lancet Neurol. 2015;14(2):162–173. DOI:10.1016/S1474-4422(14)70251-0
   PubMed Web of Science ®Google Scholar
• Chapman EJ, Edwards Z, Boland JW, et al. Practice review: evidence-based and effective management of pain in patients with advanced Cancer. Palliat Med. 2020;34(4):444–453. DOI:10.1177/0269216319896955
   PubMed Web of Science ®Google Scholar
• Caraceni A, Zecca E, Bonezzi, et al. Gabapentin for neuropathic cancer pain: a randomized controlled trial from the gabapentin cancer pain study group. J Clin Oncol. 2004;22(14):2909–2917. DOI:10.1200/JCO.2004.08.141
   PubMed Web of Science ®Google Scholar
• Kane CM, Mulvey MR, Wright S, et al. Opioids combined with antidepressants or antiepileptic drugs for cancer pain: systematic review and meta-analysis. Palliat Med. 2018;32(1):276–28658. DOI:10.1177/0269216317711826
   PubMed Web of Science ®Google Scholar
• Zajączkowska R, Kocot-Kępska M, Leppert W, et al. Mechanisms of chemotherapy-induced peripheral neuropathy. Int J Mol Sci. 2019;20(6):1451. DOI:10.3390/ijms20061451
   PubMed Web of Science ®Google Scholar
• Akhilesh Unival A, Gadepalli A, Gadepalli A, et al. Unlocking the potential of TRPV1 based siRNA therapeutics for the treatment of chemotherapy-induced neuropathic pain. Life Sci 2022 Jan 1;288:120187. DOI:10.1016/j.lfs.2021.120187
   PubMed Web of Science ®Google Scholar
• Jones KF, Wechsler S, Zulewski D, et al. Pharmacological and nonpharmacological management of chemotherapy-induced peripheral neuropathy: a scoping review of randomized controlled. Trials J Palliat Med. 2022;25(6):964–995.
   PubMed Web of Science ®Google Scholar
• Hui D, Boehlke C, Simone Ii CB. Early palliative care and the opioid crisis: ten pragmatic steps towards a more rational use of opioids. Ann Palliat Med. 2019;8(4):490–497.
   PubMed Web of Science ®Google Scholar
• Mercadante S. Too much for some and too little for others. Ann Oncol. 2022;33(4):445.
   PubMedGoogle Scholar
• Bhadelia A, De Lima L, Arreola-Ornelas H, et al. Solving the global crisis in access to pain relief: lessons from country actions. Am J Public Health. 2019;109(1):58–60. DOI:10.2105/AJPH.2018.304769
   PubMed Web of Science ®Google Scholar
• Paice JA. Risk assessment and monitoring of patients with cancer receiving opioid therapy. Oncology. 2019;24(10):1294–1298.
   Google Scholar
• Machelska H, Celik MO. Advances in achieving opioid analgesia without adverse effects. Front Pharmacol. 2018;9:1399.
   PubMed Web of Science ®Google Scholar