Pamidronate

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Abstract
Pamidronate (APD) is a potent inhibitor of bone resorption that is useful in the management of patients with osteolytic bone metastases from breast cancer or multiple myeloma, tumour- induced hypercalcaemia or Paget’s disease of bone. After intravenous administration, the drug is extensively taken up in bone, where it binds with hydroxyapatite crystals in the bone matrix. Matrix- boundpamidronate inhibits osteoclast activity by a variety of mechanisms, the most important of which appears to be prevention of the attachment of osteoclast precursor cells to bone. In patients with osteolytic bone metastases associated with either breast cancer or multiple myeloma, administration of pamidronate together with systemic antitumour therapy reduces and delays skeletal events, including pathological fracture, hypercalcaemia and the requirement for radiation treatment or surgery to bone. Pamidronate generally improves pain control. Quality- of- life and performance status scores in pamidronate recipients were generally as good as, or better than, those in patients who did not receive the drug. Overall survival does not appear to be affected by pamidronate therapy. Tumour-induced hypercalcaemia also responds well to pamidronate therapy: 70 to 100% of patients achieve normocalcaemia, generally 3 to 5 days after treatment. Response durations vary, but are commonly 3 weeks or longer. In comparative studies, pamidronate produced higher rates of normocalcaemia and longer normocalcaemic durations than other available osteoclast inhibitors, including intravenous etidronate, clodronate and plicamycin (mithramycin). In most patients with Paget’s disease of bone, intravenous pamidronate reduces bone pain and produces biochemical response. Serum alkaline phosphatase levels generally fall 50 to 70% from baseline 3 to 4 months after pamidronate treatment. Biochemical response may be prolonged. Pamidronate is well tolerated by most patients. Transient febrile reactions, sometimes accompanied by myalgias and lymphopenia, occur commonly after the first infusion of pamidronate. Other reported adverse events include transient neutropenia, mild thrombophlebitis, asymptomatic hypocalcaemia and, rarely, ocular complications (uveitis and scleritis). Pamidronate should be considered for routine use together with systemic hormonal or cytotoxic therapy in patients with breast cancer or multiple myeloma and osteolytic metastases. At present, pamidronate is the drug of choice for first- line use in the management of patients with tumour- induced hypercalcaemia. It is an effective treatment for Paget’s disease and is the treatment of choice where oral bisphosphonates are not an option. Pamidronate (APD) is an inhibitor of bone resorption that, unlike etidronate, does not appear to impair bone mineralisation at therapeutic dosages in patients with Paget’s disease. Pamidronate inhibits osteoclast activity primarily by binding with hydroxyapatite crystals in the bone matrix, preventing the attachment of osteoclast precursor cells. Other mechanisms of action of matrix-bound pamidronate may include direct inhibition of mature osteoclast function, promotion of osteoclast apoptosis and interference with osteoblast-mediated osteoclast activation. The initial plasma half-life of the drug is 3.37 mmol/L (13.5 mg/dl)], pamidronate 90mg should be administered. In patients with Paget’s disease, the optimum pamidronate dosage is not known. Recommended regimens include pamidronate 30mg daily for 3 days (US) and 180 to 210mg administered in divided doses over 6 weeks (UK). Dosage regimens based on initial biochemical disease severity may also be appropriate.