Effects of zoledronic acid on metastatic bone pain in cancer of the prostate: A randomised controlled trial

Background: Advanced cancer of the prostate often causes pain that can be severe requiring palliation with analgesics. Zoledronic acid, a third-generation bisphosphonate, has not been primarily used as an adjunct to treat pain in patients with metastatic bone secondary to advanced prostate cancer in Nigeria. The study investigated the effects of 3 doses of Zoledronic acid, at 4-weekly intervals, in addition to the analgesic regimen of oral morphine, diclofenac, paracetamol and amitriptyline, on bone pain in patients with metastatic prostate cancer . Methods: A prospective randomized open-labelled trial in which forty patients with moderate to severe bone pain due to metastatic prostate cancer were recruited after institutional ethics approval. Patients were assigned to two groups: The Control (C) group received liquid oral morphine, diclofenac, paracetamol and amitriptyline. Zoledronic acid (ZG) group received 3 doses of Zoledronic acid at 4-weekly intervals in addition to liquid morphine, diclofenac, paracetamol and amitriptyline. Severity of pain and quality of life (QoL) were measured at baseline and weekly for 12 weeks. Data were analysed using means, range, standard deviations and proportions while independent t-test was used to compare the variables between the two groups. Results: Demographic variables, baseline pain scores and quality of life between the 2 groups were similar. Therewas a statistically significant improvement in pain score in the Zoledronic acid group (1.38±0.53 vs 2.13±0.94) post-intervention, (p = 0.004). Conclusion: The administration of three doses of Zoledronic acid at 4-weekly intervals significantly improved bone pain score during the 12-weeks follow up in patients with advanced prostate cancer. Keywords: Zoledronic acid, Bone pain, Prostate cancer. Resume Contexte: Le cancer avance de la prostate provoque souvent des douleurs qui peuvent etre severes necessitant des soins palliatifs avec des analgesiques. L’acide zoledronique, un bisphosphonate de troisieme generation, n’a pas ete principalement utilise comme adjuvant pour traiter la douleur chez les patients presentant des metastases osseuses secondaires a un cancer avance de la prostate au Nigeria. L’etude a examine les effets de 3 doses d’acide zoledronique, a des intervalles de 4 semaines, en plus du regime analgesique de morphine orale, de diclofenac, de paracetamol et d’amitriptyline, sur la douleur osseuse chez les patients atteints d’un cancer metastatique de la prostate. Methodes: Un essai prospectif randomise ouvert dans lequel quarante patients souffrant de douleurs osseuses moderees a severes dues a un cancer metastatique de la prostate ont ete recrutes apres approbation ethique de l’etablissement. Les patients ont ete repartis en deux groupes: Le groupe temoin (C) a recu de la morphine orale liquide, du diclofenac, du paracetamol et de l’amitriptyline. Le groupe acide zoledronique (ZG) a recu 3 doses d’acide zoledronique a intervalles de 4 semaines en plus de la morphine liquide, du diclofenac, du paracetamol et de l’amitriptyline. La severite de la douleur et la qualite de vie (QdV) ont ete mesurees au depart et chaque semaine pendant 12 semaines. Les donnees ont ete analysees a l’aide des moyennes, de la plage, des ecarts-types et des proportions, tandis qu’un test t independant a ete utilise pour comparer les variables entre les deux groupes. Resultats: Les variables demographiques, les scores de douleur de base et la qualite de vie entre les 2 groupes etaient similaires. Il y avait une amelioration statistiquement significative du score de douleur dans le groupe acide zoledronique (1,38 ± 0,53 vs 2,13 ± 0,94) apres l’intervention, (p = 0,004). Conclusion: L’administration de trois doses d’acide zoledronique a des intervalles de 4 semaines a significativement ameliore le score de douleur osseuse au cours des 12 semaines de suivi chez les patients atteints d’un cancer de la prostate avance. Mots cles: Acide zoledronique, douleur osseuse, cancer de la prostate. Correspondence: Dr. M.O . Akinwale, Department of Anaesthesia, College of Medicine, University of Ibadan, Ibadan. Nigeria E-mail: akinsmko@yahoo.com, moakinwale@com.ui.edu.ng