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Bisphosphonates metastasis

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Publié dans : Santé & Médecine
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Bisphosphonates metastasis

  1. 1. Bisphosphonates in metastasis Dr Sitanshu
  2. 2. Introduction • Common site of Mets – breast, lung, prostrate, thyroid, kidney, MM • Skeletal complications + morbidity • Medications • Skeletal related event • Can affect survival – precluding future disease directed therapy
  3. 3. Pathophysiology • RANKL loop • Osteoclast differentiation • Positive feedback mechanism
  4. 4. Bisphosphonates mechanism of action • Structural analogs of pyrophosphate • Absorb calcium phosphate • Suppress normal functioning and maturation of osteoclast • Non nitrogeneous – eti, clo – apoptosis • Nitrogeneous – pami, zole – block HMG CoA pathway – genesis, survival, integrity
  5. 5. Summary of evidence • Cochrane meta analysis • Pain relief, reduction in analgesic consumption, increased quality of life • Do not support as primary analgesic, adjuvant to opioid / NSAID • Clinical effectiveness – 80% to 50%
  6. 6. Current recommendation 1. Osteolytic bone tumors (breast, solid) 2. Multiple myeloma 3. Hypercalcemia of malignancy 4. Aromatase inhibitor therapy
  7. 7. Screening in 1.Men aged >70 on androgen deprivation therapy 2.In breast cancer with a) family history of fractures b) weight < 70kg c) prior non traumatic # in all post menopausal women on aromatase inhibitors d) therapy induced ovarian failure in premenopausal women
  8. 8. Choosing an agent • Zoledronate, pamidronate – FDA approved • Zoledronate potency 100 times more • Peripheral / central access • Pami – 60-90mg over 90 min • Zole – 4mg over 15 min • Renal failure – slower infusion + dose adjustment according to CrCl • Monthly creatinine, calcium monitoring • Oral calcium, Vit D supplementation
  9. 9. Side effects Osteonecrosis of jaw (1%) 1.Dental evaluation before Rx 2.Delay dental extraction 3.Assessment of oral, dental hygiene 4.Avoid dentures Hypocalcemia Routine calcium, albumin monitoring before administration
  10. 10. Renal dysfunction Routine CrCl monitoring before administration Dose adjustment Slowing of infusion Fever Antipyretic Nausea Antiemetic
  11. 11. Cycle • 4 week cycle • Upto 2 years is a must • Multiple myeloma – indefinitely • If skeletal related event occurs – indefinitely, only Zoledronate • Adjunct in pain control • If for pain – for 1 year a must

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