Skip to main content
Top
Published in: International Journal of Clinical Oncology 5/2017

01-10-2017 | Original Article

Combined application of diclofenac and celecoxib with an opioid yields superior efficacy in metastatic bone cancer pain: a randomized controlled trial

Authors: Zunyong Liu, Yan Xu, Zhong-liang Liu, Yi-zhou Tian, Xiao-heng Shen

Published in: International Journal of Clinical Oncology | Issue 5/2017

Login to get access

Abstract

Background

Metastatic bone cancer pain is one of the most common clinical cancer pains and is caused by many factors. This study was conducted to explore the clinical efficacy of using two non-steroidal anti-inflammatory drugs (NSAIDs) along with an opioid in treating metastatic bone cancer pain.

Material and Method

A total of 342 patients with a pain score of 7–10 on the visual analog scale (VAS) were recruited for 4 weeks of treatment and randomly assigned to three different groups—one group received two NSAIDs (diclofenac and celecoxib), one group received diclofenac, and one group received celecoxib. All patients received morphine sulfate 10 mg/12 h with a reduction of 50% or addition of 25% each time until the VAS score was <5. The VAS score, remission rate (RR), breakthrough pain (BTP), morphine sulfate dose and side-effects among the three groups were compared.

Results

After 4 weeks of treatment, we found that using two NSAIDs along with an opioid could yield a significantly lower VAS score (p = 0.006), higher RR (p = 0.0002) and fewer incidences of BTP (p = 0.011), compared to the use of only one NSAID. Furthermore, using two NSAIDS could significantly decrease the consumption of morphine sulfate compared to using each NSAID in isolation (p = 0.0031 in week 1; p = 0.020 in week 2; p = 0.0012 in week 4). Additionally, using two NSAIDs could produce fewer incidences of dizziness (p = 0.002), constipation (p < 0.0001) and drowsiness (p < 0.0001).

Conclusion

Although limited by the relatively small samples, these results indicate that using two NSAIDs along with an opioid in treating metastatic bone cancer pain was more effective and acceptable, which is worthy of further clinical application.
Literature
1.
go back to reference Casimiro S, Luis I, Fernandes A et al (2012) Analysis of a bone metastasis gene expression signature in patients with bone metastasis from solid tumors. Clin Exp Metastasis 29(2):155–164CrossRefPubMed Casimiro S, Luis I, Fernandes A et al (2012) Analysis of a bone metastasis gene expression signature in patients with bone metastasis from solid tumors. Clin Exp Metastasis 29(2):155–164CrossRefPubMed
2.
go back to reference Egeblad M, Werb Z (2002) New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer 2(3):161–174CrossRefPubMed Egeblad M, Werb Z (2002) New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer 2(3):161–174CrossRefPubMed
3.
go back to reference Lu X, Wang Q, Hu G et al (2009) ADAMTS1 and MMP1 proteolytically engage EGF-like ligands in an osteolytic signaling cascade for bone metastasis. Genes Dev 23(16):1882–1894CrossRefPubMedPubMedCentral Lu X, Wang Q, Hu G et al (2009) ADAMTS1 and MMP1 proteolytically engage EGF-like ligands in an osteolytic signaling cascade for bone metastasis. Genes Dev 23(16):1882–1894CrossRefPubMedPubMedCentral
4.
go back to reference Jimenez-Andrade JM, Mantyh WG, Bloom AP et al (2010) Bone cancer pain. Ann N Y Acad Sci 1198(1):173–181CrossRefPubMed Jimenez-Andrade JM, Mantyh WG, Bloom AP et al (2010) Bone cancer pain. Ann N Y Acad Sci 1198(1):173–181CrossRefPubMed
6.
go back to reference Goblirsch MJ, Zwolak P, Clohisy DR (2005) Advances in understanding bone cancer pain. J Cell Biochem 96(4):682–688CrossRefPubMed Goblirsch MJ, Zwolak P, Clohisy DR (2005) Advances in understanding bone cancer pain. J Cell Biochem 96(4):682–688CrossRefPubMed
7.
go back to reference Langer C, Hirsh V (2010) Skeletal morbidity in lung cancer patients with bone metastases: demonstrating the need for early diagnosis and treatment with bisphosphonates. Lung Cancer 67(1):4–11CrossRefPubMed Langer C, Hirsh V (2010) Skeletal morbidity in lung cancer patients with bone metastases: demonstrating the need for early diagnosis and treatment with bisphosphonates. Lung Cancer 67(1):4–11CrossRefPubMed
8.
go back to reference Mantyh P (2013) Bone cancer pain: causes, consequences, and therapeutic opportunities. Pain 154(Suppl 1):S54–S62CrossRefPubMed Mantyh P (2013) Bone cancer pain: causes, consequences, and therapeutic opportunities. Pain 154(Suppl 1):S54–S62CrossRefPubMed
9.
go back to reference Ross JR, Saunders Y, Edmonds PM et al (2003) Systematic review of role of bisphosphonates on skeletal morbidity in metastatic cancer. Br Med J 327(7413):469CrossRef Ross JR, Saunders Y, Edmonds PM et al (2003) Systematic review of role of bisphosphonates on skeletal morbidity in metastatic cancer. Br Med J 327(7413):469CrossRef
10.
go back to reference McNicol E, Strassels S, Goudas L et al (2004) Nonsteroidal anti-inflammatory drugs, alone or combined with opioids, for cancer pain: a systematic review. J Clin Oncol 22(10):1975–1992CrossRefPubMed McNicol E, Strassels S, Goudas L et al (2004) Nonsteroidal anti-inflammatory drugs, alone or combined with opioids, for cancer pain: a systematic review. J Clin Oncol 22(10):1975–1992CrossRefPubMed
11.
go back to reference Mercadante S, Fulfaro F (2005) World Health Organization guidelines for cancer pain: a reappraisal. Ann Oncol. 16(Suppl 4):iv132–iv135PubMed Mercadante S, Fulfaro F (2005) World Health Organization guidelines for cancer pain: a reappraisal. Ann Oncol. 16(Suppl 4):iv132–iv135PubMed
12.
go back to reference Liu J, Liu FY, Tong ZQ et al (2013) Lysine-specific demethylase 1 in breast cancer cells contributes to the production of endogenous formaldehyde in the metastatic bone cancer pain model of rats. PLoS One 8(3):e58957CrossRefPubMedPubMedCentral Liu J, Liu FY, Tong ZQ et al (2013) Lysine-specific demethylase 1 in breast cancer cells contributes to the production of endogenous formaldehyde in the metastatic bone cancer pain model of rats. PLoS One 8(3):e58957CrossRefPubMedPubMedCentral
13.
go back to reference Coleman RE (2006) Clinical features of metastatic bone disease and risk of skeletal morbidity. Clin Cancer Res 12:6243s–6249sCrossRefPubMed Coleman RE (2006) Clinical features of metastatic bone disease and risk of skeletal morbidity. Clin Cancer Res 12:6243s–6249sCrossRefPubMed
14.
go back to reference Sevcik MA, Ghilardi JR, Peters CM et al (2005) Anti-NGF therapy profoundly reduces bone cancer pain and the accompanying increase in markers of peripheral and central sensitization. Pain 115:128–141CrossRefPubMed Sevcik MA, Ghilardi JR, Peters CM et al (2005) Anti-NGF therapy profoundly reduces bone cancer pain and the accompanying increase in markers of peripheral and central sensitization. Pain 115:128–141CrossRefPubMed
15.
go back to reference Peters CM, Lindsay TH, Pomonis JD et al (2004) Endothelin and the tumorigenic component of bone cancer pain. Neuroscience 126:1043–1052CrossRefPubMed Peters CM, Lindsay TH, Pomonis JD et al (2004) Endothelin and the tumorigenic component of bone cancer pain. Neuroscience 126:1043–1052CrossRefPubMed
17.
go back to reference Wolff RF, Aune D, Truyers C et al (2012) Systematic review of efficacy and safety of buprenorphine versus fentanyl or morphine in patients with chronic moderate to severe pain. Curr Med Res Opin 28(5):833–845CrossRefPubMed Wolff RF, Aune D, Truyers C et al (2012) Systematic review of efficacy and safety of buprenorphine versus fentanyl or morphine in patients with chronic moderate to severe pain. Curr Med Res Opin 28(5):833–845CrossRefPubMed
18.
go back to reference Fan Z, Lin H, He Q (2011) Celecoxib combined preoperative concurrent chemotherapy for rectal cancer short-term efficacy. Pract J Cancer 26(1):49–55 Fan Z, Lin H, He Q (2011) Celecoxib combined preoperative concurrent chemotherapy for rectal cancer short-term efficacy. Pract J Cancer 26(1):49–55
19.
go back to reference Setoguchi N, Takamura N, Fujita K et al (2013) A diclofenac suppository-nabumetone combination therapy for arthritic pain relief and a monitoring method for the diclofenac binding capacity of HSA site II in rheumatoid arthritis. Biopharm Drug Dispos 34(2):125–136CrossRefPubMed Setoguchi N, Takamura N, Fujita K et al (2013) A diclofenac suppository-nabumetone combination therapy for arthritic pain relief and a monitoring method for the diclofenac binding capacity of HSA site II in rheumatoid arthritis. Biopharm Drug Dispos 34(2):125–136CrossRefPubMed
20.
go back to reference Dahl JB, Kehlet H (1991) Non-steroidal anti-inflammatory drugs: ratio-nale for use in severe postoperative pain. Br J Anaesth 66:703–712CrossRefPubMed Dahl JB, Kehlet H (1991) Non-steroidal anti-inflammatory drugs: ratio-nale for use in severe postoperative pain. Br J Anaesth 66:703–712CrossRefPubMed
21.
go back to reference Chan A, Dore CJ, Ramachandra V (1996) Analgesia for day surgery. Evaluation of the effect of diclofenac given before or after surgery with or without bupivacaine infiltration. Anaesthesia 51:592–595CrossRefPubMed Chan A, Dore CJ, Ramachandra V (1996) Analgesia for day surgery. Evaluation of the effect of diclofenac given before or after surgery with or without bupivacaine infiltration. Anaesthesia 51:592–595CrossRefPubMed
22.
go back to reference White P, Sacan O, Tufanogullari B et al (2007) Effect of short-term postoperative celecoxib administration on patient outcome after outpatient laparoscopic surgery. Can J Anaesth 54(5):342–348CrossRefPubMed White P, Sacan O, Tufanogullari B et al (2007) Effect of short-term postoperative celecoxib administration on patient outcome after outpatient laparoscopic surgery. Can J Anaesth 54(5):342–348CrossRefPubMed
23.
go back to reference Yeganeh Mogadam A, Fazel MR, Parviz S (2012) Comparison of analgesic effect between gabapentin and diclofenac on post-operative pain in patients undergoing tonsillectomy. Arch Trauma Res 1(3):108–111CrossRefPubMedPubMedCentral Yeganeh Mogadam A, Fazel MR, Parviz S (2012) Comparison of analgesic effect between gabapentin and diclofenac on post-operative pain in patients undergoing tonsillectomy. Arch Trauma Res 1(3):108–111CrossRefPubMedPubMedCentral
Metadata
Title
Combined application of diclofenac and celecoxib with an opioid yields superior efficacy in metastatic bone cancer pain: a randomized controlled trial
Authors
Zunyong Liu
Yan Xu
Zhong-liang Liu
Yi-zhou Tian
Xiao-heng Shen
Publication date
01-10-2017
Publisher
Springer Japan
Published in
International Journal of Clinical Oncology / Issue 5/2017
Print ISSN: 1341-9625
Electronic ISSN: 1437-7772
DOI
https://doi.org/10.1007/s10147-017-1133-y

Other articles of this Issue 5/2017

International Journal of Clinical Oncology 5/2017 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine