PAMIDRONATE - A REVIEW OF ITS USE IN THE MANAGEMENT OF OSTEOLYTIC BONE METASTASES, TUMOR-INDUCED HYPERCALCEMIA AND PAGETS-DISEASE OF BONE

Pamidronate (APD) is a potent inhibitor of bone bone resorption that i s useful in the management of patients with osteolytic bone metastases front breast cancer or multiple myeloma, tumour-induced hypercalcaemi a or Paget's disease of bone. After intravenous administration, the dr ug is extensively taken up in bone, where it binds with hydroxyapatite crystals in the bone matrix. Matrix-bound pamidronate inhibits osteoc last activity by a variety of mechanisms, the most important of which appears to be prevention of the attachment of osteoclast precursor cel ls to bone. In patients with osteolytic bone metastases associated wit h either breast cancer or multiple myeloma, administration of pamidron ate together with systemic antitumour therapy reduces and delays skele tal events, including pathological fracture, hypercalcaemia and the re quirement for radiation treatment or surgery to bone. Pamidronate gene rally improves pain control. Quality-of-life and performance status sc ores in pamidronate recipients were generally as good as, or better th an, those in patients who did not receive the drug. Overall survival d oes not appear to be affected by pamidronate therapy. Tumour-induced h ypercalcaemia also responds well to pamidronate therapy: 70 to 100% of patients achieve normocalcaemia, generally 3 to 5 days after treatmen t. Response durations vary, but are commonly 3 weeks or longer In comp arative studies, pamidronate produced higher rates of normocalcaemia a nd longer normocalcaemic durations than other available osteoclast inh ibitors, including intravenous etidronate, clodronate and plicamycin ( mithramycin). In most patients with Paget's disease of bone, intraveno us pamidronate reduces bone pain and produces biochemical response. Se rum alkaline phosphatase levels generally fall 50 to 70% from baseline 3 to 4 months after pamidronate treatment. Biochemical response may b e 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 toget her with systemic hormonal or cytotoxic therapy in patients with breas t cancer or multiple myeloma and osteolytic metastases. At present, pa midronate is the drug of choice for first-line use in the management o f patients with tumour-induced hypercalcaemia. It is an effective trea tment for Paget's disease and is the treatment of choice where or-al b isphosphonates are not an option.