Diphosphonates for Osteolytic Metastases

Bisphosphonate Therapy in Metastatic Breast Cancer

“…The first placebo-controlled long-term bisphosphonate study comprised 34 patients with breast cancer having therapy-resistant skeletal metastases (8,9). Supportive bisphosphonate treatment (1.6 to 3.2 g Clodronate daily for one year) relieved bone pain, inhibited development of hypercalcemia, retarded the progression of bone disease and reduced the risk of bone fractures (8,9).…”

“…Supportive bisphosphonate treatment (1.6 to 3.2 g Clodronate daily for one year) relieved bone pain, inhibited development of hypercalcemia, retarded the progression of bone disease and reduced the risk of bone fractures (8,9). The survival rate was significantly better in the clodronate group, due to several hypercalcemic deaths in the placebo group.…”

Use of Bisphosphonates in Skeletal Metastasis

“…The effectiveness of bisphosphonates has been evaluated by their ability to reduce skeletal events: (1) new bone lesions (x-rays or scintigraphy) ; (2) fractures (radiologic or clinical examination) (11)(12)(13)(14)(15)(16)(17)(18)(19)(20); (3) bone pain (analgesics, visual analogue scale, pain score, requirement of irradiation or isotope therapy) (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41); (4) performance status (Karnofsky, Zubrod, ECOG) (11 -20, 31-41); (5) quality of life measures (16-20, 36, 37, 40, 41); (6) hypercalcemia (11 -21, 25, 31 -38); (7) measurements of different bone markers (11 -13, 20, 28, 30, 35 -38, 40 -44); and (8) survival (11 -13, 15, 18 -20, 34 -38, 40, 41). Study endpoints have been defined as a reduction of skeletal events and complications as well as an improvement of quality of life and pain relief.…”

“…Seven of them were performed in patients with known osteolytic metastases (11)(12)(13)(14)(15)(16)(17)(18)(19)(20). Two of the first clodronate studies are not reviewed here because of their small size (11)(12)(13)(14).…”

“…Seven of them were performed in patients with known osteolytic metastases (11)(12)(13)(14)(15)(16)(17)(18)(19)(20). Two of the first clodronate studies are not reviewed here because of their small size (11)(12)(13)(14). Table 1 presents the five largest trials: one using oral clodronate (15) and four others using either oral (16) or intravenous pamidronate (17)(18)(19)(20); design and duration of these studies, dose and route of drugs, number of patients, time of assessment and primary endpoints of skeletal events are given.…”