INTRAVENOUS PAMIDRONATE DISODIUM TREATMENT OF BONE METASTASES IN PATIENTS WITH BREAST-CANCER - A DOSE-SEEKING STUDY

Background. Treatment of the symptoms of bone metastases currently inv olves the use of narcotic medication, radiation therapy, or hormonal t herapy. Pamidronate disodium, a bisphosphonate, may prove helpful in t he palliative treatment of bone metastases in patients with breast can cer as demonstrated in this multicenter, dose-ranging trial. Methods. Ambulatory female patients age 18 years or older with breast cancer me tastatic to bone and a life expectancy of at least 3 months were eligi ble for the study. Bone metastases were confirmed by bone scan or bone survey within 6 months of enrollment. Sixty-one patients were treated as outpatients and were randomized to receive one of four intravenous pamidronate regimens for 12 weeks: 30 mg administered every 2 weeks, 60 mg every 4 weeks, 60 mg every 2 weeks, or 90 mg every 4 weeks. The primary efficacy parameter for this study was pain score. The change f rom baseline in pain score was determined for each patient at each stu dy visit and at endpoint, defined as the last postbaseline evaluation for each patient before or at week 12. Secondary efficacy variables in cluded narcotic scores, urinary calcium/creatinine and hydroxyproline/ creatinine ratios, serum osteocalcin and bone alkaline phosphatase con centrations, and bone lesion (radiologic) response. Results. At 3 mont hs, the regimens of 60 mg every 4 weeks, 60 mg every 2 weeks, and 90 m g every 4 weeks resulted in significant reduction in bone pain beginni ng by week 6 of treatment. The regimen of 30 mg every 2 weeks was not effective. Narcotic use, as reflected by narcotic scores, did not para llel the pain scores, because there was little evidence of any effect for any of the treatment groups. Reduction in bone pain was accompanie d by decreases in urinary calcium/creatinine and hydroxyproline/creati nine ratios, and bone alkaline phosphatase concentrations. Side effect s of pamidronate were mild and transient. Radiographic changes consist ent with healing of lytic lesions were observed in 15 patients (25%). Conclusion. Intravenous pamidronate is a well tolerated treatment that produced significant relief of bone pain in the majority of patients with metastatic breast cancer at the three highest doses tested.