1. P Sylvester (MBBS),D Narinesingh (MBBS,MMed,FCRadOnc)

2. Case  50 year old female  Metastatic Left Breast cancer Solitary Liver metastases ER+ PR+ HER2+ Performance status (PS) = 2  Severe lower back pain Numerical pain score = 8 Bone scan and MRI revealed bone metastases to vertebra L5

3. Bone Pain WHO Analgesic Ladder RadiotherapyBMA

4. Bone pain  Affects quality of life (Mental + Physical)  Nociceptive somatic pain  Assessment of pain by : 0-10 Numeric pain scale Faces pain rating scale  Three intensities: Mild pain(1-3); Moderate(4-6); Severe (7-10)  Psychosocial support and Patient education NCCN guidelines Version 1.2012, Adult Cancer Pain

5. WHO Analgesic Ladder http://pharmacologycorner.com/wp-content/uploads/2009/03/image.png

6. Commonly Selected Analgesics  Non opiod Acetaminophen Ibuprofen Diclofenac Arcoxia/ Celebrex  Combined ( Weak Opioid + Non opioid) Panadeine Tramacet  Opioids Morphine sulphate oral Morphine parenteral Jost L, Roila F et al. Annals of Oncology 21 (Supplement 5): v257-v260, 2010

7. Opioid Scheduling and titration  Goal  Rapid pain relief  Initial dose regime  5-7.5mg sc q 4hr  “Breakthrough dose”  transient exacerbations of pain = 10-15% of total daily dose  Revision of analgesic regime more than 4 “breakthrough” doses per day are administered  dose titration Jost L, Roila F et al. Annals of Oncology 21 (Supplement 5): v257-v260, 2010

8. Co analgesics for neuropathic pain  Antiepileptic Carbamazepine Pregabalin  Antidepressant Fluoxetine Amitryptiline  Neuroleptic Haloperidol Chlorpromazine Jost L, Roila F et al. Annals of Oncology 21 (Supplement 5): v257-v260, 2010

9. Bone modifying agents (BMA’s) [1]  Adjunctive therapy for pain control  Zoledronic acid/Donesumab  Donesumab superior in terms of delaying SRE [2]  Calcium and Vitamin D supplementation  Monitor creatinine clearance for intravenous bisphosphonates  Monitor calcium levels  Dental exam and preventive dentistry before using a BMA [1]Van Poznak CH, Temin S, Yee GC, et al: American Society of Clinical Oncology Executive Summary of the Clinical Practice Guideline Update on the role of Bone-Modifying Agents in Metastatic Breast Cancer. J Clin Oncol 29:1221-1227, 2011 [2] Stopeck A, et al. J Clin Oncol. 2010;28:5132-5139.

10. Palliative radiotherapy  Specific and Critical efficacy in pain relief [1]  Clinical mark up Areas of maximal pain intensity Whole pelvis radiation Radiation to spine  Doses (tailored to Performance Status) 8Gy in 1# / 30Gy in 10# / 20Gy in 5# Studies show 8Gy in 1# = 30Gy in 10# [2]  Bone targeted radioisotopes E.g.Strontium-89 [1] Jost L, Roila F et al. Annals of Oncology 21 (Supplement 5): v257-v260, 2010 [2] Hartsell WF, Scott CB, Bruner DW, et al. Randomized trial of short- versus long-course radiotherapy for palliation of painful bone metastases. J Natl Cancer Inst. 2005;97:798-804.

11. Case Management  Initial Bone Pain Management Zoledronic acid 4mg iv q 4weeks Oral Morphine  Mild relief after initial management  Also developed BL Lower limb paresthesiae 2 o tumor infiltration  Palliative RT to L5 (30Gy in10#)  Had good pain relief after RT Now on Pregabalin After one year of BMA therapy ○ Pain score = 1 ○ PS = 0

12. IN SUMMARY Mild to Moderate Non opioids ± weak opioids Zoledronic acid Severe Opioids Zoledronic acid Refractory pain Palliative RT Reassess pain