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Dear editor:
We have read with interest the article by Lobos Urbina and Peña Durán (Medwave 2016;16(Suppl3):e6539 doi: 10.5867/medwave.2016.6539) [1]. Cancer pain is a complex symptom, its control is influenced by many factors: the pain mechanism (neuropathic versus non neuropathic), pain characteristics (continuous versus incidental), previous opioid dose, cognitive function, psychological distress, tolerance and past history of alcohol or drugs [2].The majority of the studies cited by Lobos Urbina and Peña Durán did not control these variables.
Pre-clinical data suggest the utility of cannabinoids for treating pain [3]. Clinical evidence has reported that cannabinoids are useful drugs for treating chronic pain, neuropathic pain, and that refractory to the standard treatments [4]. In systematic reviews and meta-analysis, patients with cancer pain have been heterogeneously represented in comparison with pain due to other conditions. The most encouraging result has been reported in the treatment of post chemotherapy neuropathic pain and irruptive pain [5],[6].
Secondary effects have been the most frequent argument in view to avoid the use of cannabinoids in the treatment of cancer pain, although other drugs used with the same goal also have important risks. Therefore, judgement on relative risk/benefits should be considered within the broader context of risk/benefit of other agents as well.
Nowadays cannabinoids cannot be considered as a standard treatment in cancer pain neither for all types of pain due to cancer. There are other drugs and treatments with proved effectiveness that remain as the first treatment options. However, nearly 20% of patients will develop a refractory pain in spite of an optimal treatment.
Lobos Urbina and Peña Durán express that any analgesic effect of cannabinoids would be small and, due to its risk/benefit balance, patients and physicians should be against its use. We think this is a ventured asseveration because the authors recognize the high probability that the results of their meta-analysis may change in the future. If there is evidence suggesting a specific role of cannabinoids, why physicians should be against that? Why should we give up exploring its role in cancer patients without other treatment options? Why not study cannabinoids in cooperative and well-designed studies?
We appreciate that the study of Lobos Urbina and Peña Durán addresses this issue because of the connotation of medical use of cannabis in the public opinion and the recent authorization by the Instituto de Salud Pública to commercialize Sativex ® in Chile.
From the editor
The authors originally submitted this article in Spanish and English. The Journal has not copyedited this English version.
Declaration of conflicts of interest
Authors declare no conflicts of interest.
Financing
The authors declare not having received any funding whatsoever for writing this letter.
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Autor:
Andrés Vargas Mondaca[1]
Citación: Vargas Mondaca A. Cannabinoids and cancer pain: some considerations. Medwave 2016 Nov;16(10):e6597 doi: 10.5867/medwave.2016.10.6597
Fecha de publicación: 3/11/2016
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Nombre/name: Diego Nicolás Lobos
Fecha/date: 2016-12-24 21:51:09
Comentario/comment:
En primer término, queremos agradecer el interés mostrado por Vargas [1] en el artÃculo recientemente publicado por esta revista [2]; sin embargo, queremos clarificar algunos de los puntos expuestos en la carta al editor.
Como bien señala Vargas, en la gran mayorÃa de los estudios no se controlaron algunas de las variables que reconocidamente afectan en la percepción tanto del dolor como de su alivio. Esta es una consideración válida y que resalta la necesidad de estudios de mejor calidad metodológica que traten el problema. Lamentablemente, al analizar la evidencia disponible no podemos ignorar los datos existentes solo por este motivo; por el contrario, debemos considerarlos al momento de evaluar la certeza del conjunto de la evidencia.
Por otro lado, nuestro resumen de evidencia evalúa los efectos analgésicos de los cannabinoides en el manejo del dolor de tipo oncológico, analizando la evidencia que se puede obtener de las revisiones sistemáticas actualmente disponibles. No fueron evaluados sus efectos en el dolor de tipo neuropático (derivado de la patologÃa de base o su tratamiento) en forma particular ni especÃfica, ni tampoco otros tipos de dolor, ya que presentan mecanismos fisiopatológicos que consideramos diferentes y que han demostrado respuesta a terapias también de forma diferenciada. En ese sentido bajo ningún punto de vista se pretende ampliar las conclusiones a un grupo de pacientes que este estudio no representa, más aún cuando existe un gran conjunto de evidencia que responde a esa pregunta en particular y que debe ser analizado [3], [4], [5], [6], [7], [8], [9], [10], [11].
En otro aspecto, no creemos que nuestra conclusión sobre el balance riesgo beneficio sea aventurada. Es cierto que la certeza de la evidencia es muy baja para el efecto analgésico, y que podrÃa cambiar a futuro, sin embargo, existe certeza respecto de sus efectos adversos. A pesar de lo expuesto por Vargas respecto de los efectos adversos de los medicamentos de uso habitual en el manejo del dolor, estos medicamentos sà han demostrado ser útiles para la reducción del dolor [12], [13], [14], [15], [16]. En ese contexto, actualmente no podemos sino concluir que no es recomendable indicar el uso de cannabinoides en la práctica clÃnica habitual, fuera de un estudio clÃnico.
Finalmente, debemos aclarar que no pretendemos, con nuestro artÃculo, contribuir a “prohibir†el uso de los cannabinoides o a evitar posibles nuevas investigaciones sobre sus beneficios; por el contrario, reconocemos que es una materia que debe seguir siendo estudiada, sin embargo, su uso parece justificado en esos contextos, de investigación, ya que, como concluimos en nuestro artÃculo, la evidencia actualmente disponible no apoya su incorporación a la práctica clÃnica en el manejo dolor crónico de tipo oncológico.
Referencias:
1. Vargas Mondaca A. Cannabinoids and cancer pain: some considerations. Medwave. 2016 Nov 3;16(10):e6597. doi: 10.5867/medwave.2016.10.6597. Spanish, English. PubMed PMID: 27922583.
2. Lobos Urbina D, Peña Durán J. Are cannabinoids effective for treatment of pain in patients with active cancer? Medwave. 2016 Sep 14;16 Suppl 3:e6539. doi: 10.5867/medwave.2016.6539. English, Spanish. PubMed PMID: 27635982.
3. CADTH. Cannabinoids for the management of neuropathic pain: review of clinical effectiveness [Internet]. CADTH Reports. Ottawa; 2010. Available from: https://www.cadth.ca/cannabinoids-management-neuropathic-pain-review-clinical-effectiveness-0
4. Boychuk DG, Goddard G, Mauro G, Orellana MF. The effectiveness of cannabinoids in the management of chronic nonmalignant neuropathic pain: a systematic review. J Oral Facial Pain Headache. 2015 Winter;29(1):7-14. doi: 10.11607/ofph.1274. Review. PubMed PMID: 25635955.
5. Iskedjian M, Bereza B, Gordon A, Piwko C, Einarson TR. Meta-analysis of cannabis based treatments for neuropathic and multiple sclerosis-related pain. Curr Med Res Opin. 2007 Jan;23(1):17-24. PubMed PMID: 17257464.
6. Lynch ME, Ware MA. Cannabinoids for the Treatment of Chronic Non-Cancer Pain: An Updated Systematic Review of Randomized Controlled Trials. J Neuroimmune Pharmacol. 2015 Jun;10(2):293-301. doi: 10.1007/s11481-015-9600-6. Review. PubMed PMID: 25796592.
7. Lynch ME, Campbell F. Cannabinoids for treatment of chronic non-cancer pain; a systematic review of randomized trials. Br J Clin Pharmacol. 2011 Nov;72(5):735-44. doi: 10.1111/j.1365-2125.2011.03970.x. Review. PubMed PMID: 21426373; PubMed Central PMCID: PMC3243008.
8. Andreae MH, Carter GM, Shaparin N, Suslov K, Ellis RJ, Ware MA, Abrams DI, Prasad H, Wilsey B, Indyk D, Johnson M, Sacks HS. Inhaled Cannabis for Chronic Neuropathic Pain: A Meta-analysis of Individual Patient Data. J Pain. 2015 Dec;16(12):1221-32. doi: 10.1016/j.jpain.2015.07.009. Review. PubMed PMID: 26362106; PubMed Central PMCID: PMC4666747.
9. Snedecor SJ, Sudharshan L, Cappelleri JC, Sadosky A, Mehta S, Botteman M. Systematic review and meta-analysis of pharmacological therapies for painful diabetic peripheral neuropathy. Pain Pract. 2014 Feb;14(2):167-84. doi: 10.1111/papr.12054. Review. PubMed PMID: 23534696.
10. Snedecor SJ, Sudharshan L, Cappelleri JC, Sadosky A, Desai P, Jalundhwala YJ, Botteman M. Systematic review and comparison of pharmacologic therapies for neuropathic pain associated with spinal cord injury. J Pain Res. 2013 Jul 11;6:539-47. doi: 10.2147/JPR.S45966. PubMed PMID: 23874121; PubMed Central PMCID: PMC3712802.
11. Phillips TJ, Cherry CL, Cox S, Marshall SJ, Rice AS. Pharmacological treatment of painful HIV-associated sensory neuropathy: a systematic review and meta-analysis of randomised controlled trials. PLoS One. 2010 Dec 28;5(12):e14433. doi: 10.1371/journal.pone.0014433. Review. PubMed PMID: 21203440; PubMed Central PMCID: PMC3010990.
12. Zeppetella G, Davies A, Eijgelshoven I, Jansen JP. A network meta-analysis of the efficacy of opioid analgesics for the management of breakthrough cancer pain episodes. J Pain Symptom Manage. 2014 Apr;47(4):772-785.e5. doi: 10.1016/j.jpainsymman.2013.05.020. Review. PubMed PMID: 23981487.
13. Wiffen PJ, Wee B, Moore RA. Oral morphine for cancer pain. Cochrane Database Syst Rev. 2016 Apr 22;4:CD003868. doi: 10.1002/14651858.CD003868.pub4. Review. PubMed PMID: 27105021.
14. Schmidt-Hansen M, Bennett MI, Arnold S, Bromham N, Hilgart JS. Oxycodone for cancer-related pain. Cochrane Database Syst Rev. 2015 Feb 27;(2):CD003870. doi: 10.1002/14651858.CD003870.pub5. Review. PubMed PMID: 25723351.
15. Nicholson AB. Methadone for cancer pain. Cochrane Database Syst Rev. 2007 Oct 17;(4):CD003971. Review. PubMed PMID: 17943808.
16. Wiffen PJ, Derry S, Naessens K, Bell RF. Oral tapentadol for cancer pain. Cochrane Database Syst Rev. 2015 Sep 25;(9):CD011460. doi: 10.1002/14651858.CD011460.pub2. Review. PubMed PMID: 26403220.
Nombre/name: Diego Nicolás Lobos
Fecha/date: 2016-12-30 14:48:36
Comentario/comment:
Referencias:
1. Vargas Mondaca A. Cannabinoids and cancer pain: some considerations. Medwave. 2016 Nov 3;16(10):e6597. doi: 10.5867/medwave.2016.10.6597. Spanish, English. PubMed PMID: 27922583.
2. Lobos Urbina D, Peña Durán J. Are cannabinoids effective for treatment of pain in patients with active cancer? Medwave. 2016 Sep 14;16 Suppl 3:e6539. doi: 10.5867/medwave.2016.6539. English, Spanish. PubMed PMID: 27635982.
3. CADTH. Cannabinoids for the management of neuropathic pain: review of clinical effectiveness [Internet]. CADTH Reports. Ottawa; 2010. Available from: https://www.cadth.ca/cannabinoids-management-neuropathic-pain-review-clinical-effectiveness-0
4. Boychuk DG, Goddard G, Mauro G, Orellana MF. The effectiveness of cannabinoids in the management of chronic nonmalignant neuropathic pain: a systematic review. J Oral Facial Pain Headache. 2015 Winter;29(1):7-14. doi: 10.11607/ofph.1274. Review. PubMed PMID: 25635955.
5. Iskedjian M, Bereza B, Gordon A, Piwko C, Einarson TR. Meta-analysis of cannabis based treatments for neuropathic and multiple sclerosis-related pain. Curr Med Res Opin. 2007 Jan;23(1):17-24. PubMed PMID: 17257464.
6. Lynch ME, Ware MA. Cannabinoids for the Treatment of Chronic Non-Cancer Pain: An Updated Systematic Review of Randomized Controlled Trials. J Neuroimmune Pharmacol. 2015 Jun;10(2):293-301. doi: 10.1007/s11481-015-9600-6. Review. PubMed PMID: 25796592.
7. Lynch ME, Campbell F. Cannabinoids for treatment of chronic non-cancer pain; a systematic review of randomized trials. Br J Clin Pharmacol. 2011 Nov;72(5):735-44. doi: 10.1111/j.1365-2125.2011.03970.x. Review. PubMed PMID: 21426373; PubMed Central PMCID: PMC3243008.
8. Andreae MH, Carter GM, Shaparin N, Suslov K, Ellis RJ, Ware MA, Abrams DI, Prasad H, Wilsey B, Indyk D, Johnson M, Sacks HS. Inhaled Cannabis for Chronic Neuropathic Pain: A Meta-analysis of Individual Patient Data. J Pain. 2015 Dec;16(12):1221-32. doi: 10.1016/j.jpain.2015.07.009. Review. PubMed PMID: 26362106; PubMed Central PMCID: PMC4666747.
9. Snedecor SJ, Sudharshan L, Cappelleri JC, Sadosky A, Mehta S, Botteman M. Systematic review and meta-analysis of pharmacological therapies for painful diabetic peripheral neuropathy. Pain Pract. 2014 Feb;14(2):167-84. doi: 10.1111/papr.12054. Review. PubMed PMID: 23534696.
10. Snedecor SJ, Sudharshan L, Cappelleri JC, Sadosky A, Desai P, Jalundhwala YJ, Botteman M. Systematic review and comparison of pharmacologic therapies for neuropathic pain associated with spinal cord injury. J Pain Res. 2013 Jul 11;6:539-47. doi: 10.2147/JPR.S45966. PubMed PMID: 23874121; PubMed Central PMCID: PMC3712802.
11. Phillips TJ, Cherry CL, Cox S, Marshall SJ, Rice AS. Pharmacological treatment of painful HIV-associated sensory neuropathy: a systematic review and meta-analysis of randomised controlled trials. PLoS One. 2010 Dec 28;5(12):e14433. doi: 10.1371/journal.pone.0014433. Review. PubMed PMID: 21203440; PubMed Central PMCID: PMC3010990.
12. Zeppetella G, Davies A, Eijgelshoven I, Jansen JP. A network meta-analysis of the efficacy of opioid analgesics for the management of breakthrough cancer pain episodes. J Pain Symptom Manage. 2014 Apr;47(4):772-785.e5. doi: 10.1016/j.jpainsymman.2013.05.020. Review. PubMed PMID: 23981487.
13. Wiffen PJ, Wee B, Moore RA. Oral morphine for cancer pain. Cochrane Database Syst Rev. 2016 Apr 22;4:CD003868. doi: 10.1002/14651858.CD003868.pub4. Review. PubMed PMID: 27105021.
14. Schmidt-Hansen M, Bennett MI, Arnold S, Bromham N, Hilgart JS. Oxycodone for cancer-related pain. Cochrane Database Syst Rev. 2015 Feb 27;(2):CD003870. doi: 10.1002/14651858.CD003870.pub5. Review. PubMed PMID: 25723351.
15. Nicholson AB. Methadone for cancer pain. Cochrane Database Syst Rev. 2007 Oct 17;(4):CD003971. Review. PubMed PMID: 17943808.
16. Wiffen PJ, Derry S, Naessens K, Bell RF. Oral tapentadol for cancer pain. Cochrane Database Syst Rev. 2015 Sep 25;(9):CD011460. doi: 10.1002/14651858.CD011460.pub2. Review. PubMed PMID: 26403220.
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Lobos Urbina D, Peña Durán J. Are cannabinoids effective for treatment of pain in patients with active cancer?. Medwave 2016; 16(Suppl3):e6539. | CrossRef | PubMed |Bruera E, Schoeller T, Wenk R et al. A prospective multicenter assessment of the Edmonton staging system for cancer pain. J Pain Symptom Manage. 1995 Jul;10(5):348-55. | PubMed |Elikkottil J, Gupta P, Gupta K. The Analgesic Potential of Cannabinoids. J Opioid Manag. 2009 Nov-Dec;5(6):341-57. | PubMed |Whiting PF, Wolff RF, Deshpande S, Di Nisio M, Duffy S, Hernandez AV, et al. Cannabinoids for Medical Use: A Systematic Review and Meta-analysis. JAMA. 2015 Jun 23-30;313(24):2456-73. | CrossRef | PubMed |
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