Bisphosphonates in metastasis

Dr Sitanshu

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

Pathophysiology

• RANKL loop• Osteoclast

differentiation• Positive

feedback mechanism

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

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%

Current recommendation

1. Osteolytic bone tumors (breast, solid)

2. Multiple myeloma3. Hypercalcemia of malignancy4. Aromatase inhibitor therapy

Screening in1.Men aged >70 on androgen

deprivation therapy2.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

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

Side effects

Osteonecrosis of jaw (1%)1.Dental evaluation before Rx2.Delay dental extraction3.Assessment of oral, dental hygiene4.Avoid dentures

Hypocalcemia Routine calcium, albumin monitoring

before administration

Renal dysfunctionRoutine CrCl monitoring before administrationDose adjustmentSlowing of infusion

Fever Antipyretic

NauseaAntiemetic

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