Modern pharmacological approaches to pain management in oncology patients, part I (narrative review)

Introduction. In Part I of this review, we collate and analyze established approaches to cancer pain management, encompassing routine, emerging, and promising methods. Emphasis is placed on transparent search procedures, comparability of evidence, and the practical applicability of conclusions for both bedside clinicians and the development of methodological guidance and recommendations.

The objective was to critically synthesize the evidence on the effectiveness and safety of pharmacological analgesia in adult oncology patients and to delineate key areas of uncertainty to guide further research and implementation.

Materials and methods. We conducted a narrative review with elements of a structured search (October 2025; updated on 23 Oct 2025). Sources included PubMed/MEDLINE, Embase, the Cochrane Library, Scopus, Web of Science, and eLIBRARY.ru; clinical trial registries (ClinicalTrials. gov and WHO ICTRP); and documents from relevant professional societies. The primary time window was 2000–2025 (with no strict limits for foundational studies). 63 sources were included in the final analysis for Part I.

Sections. The review addresses pharmacological strategies for cancer-related pain. The lowest therapeutic responsiveness, despite the need for rapid symptom control, is typically observed in nociplastic pain (central sensitization). High resistance is also characteristic of mixed pain syndromes in which neuropathic pain coexists with a predominant nociceptive component. Refractory central neuropathic pain frequently necessitates the use of ketamine and cannabinoids; however, the evidence base is constrained by small randomized controlled trials and a considerable burden of adverse effects.

Conclusions. Standard analgesic approaches provide acceptable effectiveness with well-characterized adverse reactions and contraindications. Nevertheless, a substantial cohort of patients continues to require more contemporary, safer, and pathophysiology-informed strategies for cancer pain control.

1. Arbuck D. M., Abuzarova G. R., Alekseeva G. S. Opioids in pain syndrome management (part 1). Messenger of anesthesiology and resuscitation, 2017, vol. 14, no. 3, pp. 58–67. (In Russ.). https://doi.org/10.21292/2078-5658-2017-14-3-58-67.

2. Potievskaya V. I., Shvetsky F. M., Varchenko N. N. et al. Effect of xenon–oxygen inhalations on the psychovegetative component of pain syndrome after abdominal cancer surgery. Russian Journal of Anesthesiology and Reanimatology, 2023, no. 4, pp. 56–65. (In Russ.). https://doi.org/10.17116/anaesthesiology202304156.

3. Shpichko A. I., Cherpakov R. A., Shabanov A. K. et al. Effects of xenon on neuroinflammation markers: a prospective pilot study. Sklifosovsky Journal Emergency Medical Care, 2023, vol. 12, no. 2, pp. 250–258. (In Russ.). https://doi.org/10.23934/2223-9022-2023-12-2-250-258.

4. Ako T., Ørnskov M. P., Lykke C. et al. Prevalence of opioid misuse in patients with cancer: a systematic review and meta-analysis. Br J Cancer, 2024, vol. 131, no. 6, pp. 1014–1020. https://doi.org/10.1038/s41416-024-02802-8.

5. Barrington N. A., Coleman R. E., Erlebacher J. A. et al. Randomized, placebo-controlled trial of clodronate in patients with operable breast cancer. J Clin Oncol, 1993, vol. 11, no. 1, pp. 59–65.

6. Barros M., Liang M., Iannucci N. et al. Xenon and Argon as Neuroprotective Treatments for Perinatal Hypoxic–Ischemic Brain Injury: A Preclinical Systematic Review and Meta-Analysis. Anesthesia & Analgesia, 2025, vol. 141, no. 2, pp. 327–342. https://doi.org/10.1213/ANE.0000000000007223.

7. Chakraborty P., Borgohain M. Evaluating pregabalin in cancer patients with chronic neuropathic pain and depression: an observational case series. World J Clin Oncol, 2025, vol. 16, no. 4, pp. 104827. https://doi.org/10.5306/wjco.v16.i4.104827.

8. Chang T. W., Yang F. Y., Liu Y. C. et al. Gabapentinoids for chemotherapy-induced peripheral neuropathy: systematic review and meta-analysis. BMJ Support Palliat Care, 2024, vol. 14, no. 3, pp. 269–278. https://doi.org/10.1136/spcare-2023-004362.

9. Coleman R. E., Body J. J., Aapro M. et al. Role of bone-modifying agents in metastatic breast cancer. J Clin Oncol, 2017, vol. 35, no. 34, pp. 3978–3991.

10. Culp C., Kim H. K., Abdi S. Ketamine use for cancer and chronic pain management. Front Pharmacol, 2021, vol. 11, pp. 599721. https://doi.org/10.3389/fphar.2020.599721.

11. Davis M. P. Novel drug treatments for pain in advanced cancer and serious illness: a focus on neuropathic pain and chemotherapy-induced peripheral neuropathy. Palliative Care and Social Practice, 2024, vol. 18. https://doi.org/10.1177/26323524241266603.

12. Denton A., Shaw J. Corticosteroids in palliative care – perspectives of clinicians involved in prescribing: a qualitative study. BMC Palliat Care, 2014, vol. 13, no. 1, pp. 50. https://doi.org/10.1186/1472-684X-13-50.

13. Fallon M., Giusti R., Aielli F. et al. Management of cancer pain in adult patients: ESMO Clinical Practice Guidelines. Ann Oncol, 2018, vol. 29, Suppl 4, pp. iv166–iv191. https://doi.org/10.1093/annonc/mdy152.

14. Forster M., Deal A. M., Page A. et al. Dose delay, dose reduction, and early treatment discontinuation in Black and White women receiving chemotherapy for nonmetastatic breast cancer. The Oncologist, 2024, vol. 29, no. 10, pp. e1246–e1259. https://doi.org/10.1093/oncolo/oyae150.

15. Gallaway M. S., Townsend J. S., Shelby D. et al. Pain Among Cancer Survivors. Prev Chronic Dis, 2020, vol. 17, pp. E54. https://doi.org/10.5888/pcd17.190367.

16. García Sáenz J. A., López Tarruella S., García Paredes B. et al. Osteonecrosis of the jaw as an adverse bisphosphonate event: three cases of bone metastatic prostate cancer patients treated with zoledronic acid. Med Oral Patol Oral Cir Bucal, 2007, vol. 12, no. 5, pp. E351–E356.

17. Garzón–Rodríguez C., Casals Merchan M., Calsina–Berna A. et al. Lidocaine 5% patches as an effective short-term co-analgesic in cancer pain. Preliminary results. Support Care Cancer, 2013, vol. 21, no. 11, pp. 3153–8. https://doi.org/10.1007/s00520-013-1948-7.

18. Griffiths H. M. Low-dose ketamine infusions for chronic pain management: Does this qualify as evidence-based practice? Br J Pain, 2023, vol. 17, no. 5, pp. 457–467. https://doi.org/10.1177/20494637231182804.

19. Hatano Y., Matsuoka H., Lam L. et al. Side effects of corticosteroids in patients with advanced cancer: a systematic review. Support Care Cancer, 2018, vol. 26, no. 12, pp. 3979–3983. https://doi.org/10.1007/s00520-018-4339-2.

20. Henry D. H., Costa L., Goldwasser F. et al. Randomized, double-blind study of denosumab versus zoledronic acid in the treatment of bone metastases in patients with advanced cancer (excluding breast and prostate cancer) or multiple myeloma. J Clin Oncol, 2011, vol. 29, no. 9, pp. 1125–32. https://doi.org/10.1200/JCO.2010.31.3304.

21. Herbert A., Hardy J. Medicinal cannabis use in palliative care. Aust J Gen Pract, 2021, vol. 50, no. 6, pp. 363–368. https://doi.org/10.31128/AJGP-02-21-5831.

22. Holsträter T. F., Georgieff M., Föhr K. J. et al. Intranasal application of xenon reduces opioid requirement and postoperative pain in patients undergoing major abdominal surgery: a randomized controlled trial. Anesthesiology, 2011, vol. 115, no. 2, pp. 398–407. https://doi.org/10.1097/ALN.0b013e318225cee5.

23. Hussein A., Digges M., Chang S. et al. Pharmacovigilance in hospice/palliative care: Net effect of amitriptyline or nortriptyline on neuropathic pain: UTS/IMPACCT Rapid programme international consecutive cohort. Palliative Medicine, 2022, vol. 36, no. 6, pp. 938–944. https://doi.org/10.1177/02692163221085855.

24. Jabbari S., Sadreddini K., Molaei M. Antidepressant use for mental health treatment of cancer patients; is it optimised? Gastrointestinal Oncology: Management and Care, 2025, vol. 2, no. 1. https://doi.org/10.1080/29937817.2025.2474250.

25. Jiao J., Fan J., Zhang Y. et al. Efficacy and Safety of Ketamine to Treat Cancer Pain in Adult Patients: A Systematic Review. J Pain Symptom Manage, 2024, vol. 67, no. 3, pp. e185–e210. https://doi.org/10.1016/j.jpainsymman.2023.11.004.

26. Lee J., Currow D., Lovell M. et al. Lidocaine for neuropathic cancer pain (LiCPain): study protocol for a mixed-methods pilot study. BMJ Open, 2023, vol. 13, no. 2, pp. e066125. https://doi.org/10.1136/bmjopen-2022-066125.

27. Lee J. T., Sanderson C. R., Xuan W. et al. Lidocaine for cancer pain in adults: a systematic review and meta-analysis. J Palliat Med, 2019, vol. 22, no. 3, pp. 326–334. https://doi.org/10.1089/jpm.2018.0257.

28. Leppert W., Buss T. The role of corticosteroids in the treatment of pain in cancer patients. Curr Pain Headache Rep, 2012, vol. 16, no. 4, pp. 307–13. https://doi.org/10.1007/s11916-012-0273-z.

29. Li X., Chen H., Zhu Y. et al. Lidocaine reduces pain behaviors by inhibiting the expression of Nav1.7 and Nav1.8 and diminishing sympathetic sprouting in SNI rats. Mol Pain, 2022, vol. 18, pp. 17448069221124925. https://doi.org/10.1177/17448069221124925.

30. Lossignol D. A little help from steroids in oncology. J Transl Int Med, 2016, vol. 4, no. 1, pp. 52–54. https://doi.org/10.1515/jtim-2016-0011.

31. Loveday B. A., Sindt J. Ketamine protocol for palliative care in cancer patients with refractory pain. J Adv Pract Oncol, 2015, vol. 6, no. 6, pp. 555–61.

32. McGuigan S., Marie D. J., O’Bryan L. J. et al. The cellular mechanisms associated with the anesthetic and neuroprotective properties of xenon: a systematic review of the preclinical literature. Front Neurosci, 2023, vol. 17, pp. 1225191. https://doi.org/10.3389/fnins.2023.1225191.

33. Mulvey M. R., Paley C. A., Schuberth A. et al. Neuropathic pain in cancer: what are the current guidelines? Curr Treat Options Oncol, 2024, vol. 25, no. 9, pp. 1193–1202. https://doi.org/10.1007/s11864-024-01248-7.

34. Nalamachu S., Crockett R. S., Gammaitoni A. R. et al. A comparison of the lidocaine patch 5% vs naproxen 500 mg twice daily for the relief of pain associated with carpal tunnel syndrome: a 6-week, randomized, parallel-group study. MedGenMed, 2006, vol. 8, no. 3, pp. 33.

35. Navez M. L., Monella C., Bösl I. et al. 5% Lidocaine Medicated Plaster for the Treatment of Postherpetic Neuralgia: A Review of the Clinical Safety and Tolerability. Pain Ther, 2015, vol. 4, no. 1, pp. 1–15. https://doi.org/10.1007/s40122-015-0034-x.

36. Nijs J., Lahousse A., Kapreli E. et al. Nociplastic pain criteria or recognition of central sensitization? Pain phenotyping in the past, present and future. J Clin Med, 2021, vol. 10, no. 15, pp. 3203. https://doi.org/10.3390/jcm10153203.

37. Paice J. A., Bohlke K., Barton D. et al. Use of opioids for adults with pain from cancer or cancer treatment: ASCO guideline. J Clin Oncol, 2023, vol. 41, no. 4, pp. 914–930. https://doi.org/10.1200/JCO.22.02198.

38. Portenoy R. K., Ganae–Motan E. D., 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, vol. 13, no. 5, pp. 438–49. https://doi.org/10.1016/j.jpain.2012.01.003.

39. Prommer E. E. Ketamine for pain: an update of uses in palliative care. J Palliat Med, 2012, vol. 15, no. 4, pp. 474–83. https://doi.org/10.1089/jpm.2011.0244.

40. Radkhah H., Esfandbod M., Khadembashiri M. A. et al. Comparative Study of the Effects of Duloxetine and Venlafaxine on Acute Symptomatic Taxane-induced Neuropathy in Breast Cancer Patients: A Randomized Clinical Trial. J Community Hosp Intern Med Perspect, 2024, vol. 14, no. 1, pp. 18–24. https://doi.org/10.55729/2000-9666.1289.

41. Rav E., Sheth R., Ahmad A. H. Systemic lidocaine infusions for pediatric patients with cancer-related pain. Children (Basel), 2022, vol. 9, no. 12, pp. 1934. https://doi.org/10.3390/children9121934.

42. 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, vol. 15, pp. 318. https://doi.org/10.1186/1745-6215-15-318.

43. Sami S. H. A. Assessment of analgesics and alternative approaches in cancer pain management: A cross-sectional study. Journal of Oncology Pharmacy Practice, 2025. https://doi.org/10.1177/10781552251381791.

44. Saracoglu I., Isintas M., Turk A. et al. Phenotyping of chronic pain in breast cancer survivors: an original study using the cancer pain phenotyping (CANPPHE) Network multidisciplinary international guidelines. Support Care Cancer, 2024, vol. 32, no. 6, pp. 383. https://doi.org/10.1007/s00520-024-08594-0.

45. Snijders R. A. H., Brom L., Theunissen M. et al. Update on prevalence of pain in patients with cancer 2022: a systematic literature review and meta-analysis. Cancers (Basel), 2023, vol. 15, no. 3, pp. 591. https://doi.org/10.3390/cancers15030591.

46. Song S. Y., Ko Y. B., Kim H. et al. Effect of serotonin–norepinephrine reuptake inhibitors for patients with chemotherapy-induced painful peripheral neuropathy: A meta-analysis. Medicine (Baltimore), 2020, vol. 99, no. 1, pp. e18653. https://doi.org/10.1097/MD.0000000000018653.

47. D’Souza R. S., Saini C., Hussain N. et al. Global estimates of prevalence of chronic painful neuropathy among patients with chemotherapy-induced peripheral neuropathy: systematic review and meta-analysis of data from 28 countries, 2000–24. Reg Anesth Pain Med, 2025, rapm-2024-106229. https://doi.org/10.1136/rapm-2024-106229.

48. Stopeck A. T., Lipton A., Body J. J. et al. Randomized, double-blind study of denosumab versus zoledronic acid in patients with advanced cancer metastatic to bone. J Clin Oncol, 2011, vol. 29, no. 9, pp. 1125–1132.

49. Yasaei R., Katta S., Patel P. et al. Gabapentin. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing, 2024.

50. Zgaia A. O., Irimie A., Sandesc D. et al. The role of ketamine in the treatment of chronic cancer pain. Clujul Med, 2015, vol. 88, no. 4, pp. 457–61. https://doi.org/10.15386/cjmed-500.