J F Simeone

Efficacy of Pamidronate in Reducing Skeletal Events in Patients with Advanced Multiple Myeloma

BACKGROUND Skeletal complications are a major clinical manifestation of multiple myeloma. These complications are caused by soluble factors that stimulate osteoclasts to resorb bone. Bisphosphonates such as pamidronate inhibit osteoclastic activity and reduce bone resorption. METHODS Patients with stage III multiple myeloma and at least one lytic lesion received either placebo or pamidronate (90 mg) as a four-hour intravenous infusion given every four weeks for nine cycles in addition to antimyeloma therapy. The patients were stratified according to whether they were receiving first-line (stratum 1) or second-line (stratum 2) antimyeloma chemotherapy at entry into the study. Skeletal events (pathologic fracture, irradiation of or surgery on bone, and spinal cord compression), hypercalcemia (symptoms or a serum calcium concentration > or = 12 mg per deciliter [3.0 mmol per liter]), bone pain, analgesic-drug use, performance status, and quality of life were assessed monthly. RESULTS Among 392 treated patients, the efficacy of treatment could be evaluated in 196 who received pamidronate and 181 who received placebo. The proportion of patients who had any skeletal events was significantly lower in the pamidronate group (24 percent) than in the placebo group (41 percent, P < 0.001), and the reduction was evident in both stratum 1 (P = 0.04) and stratum 2 (P = 0.004). The patients who received pamidronate had significant decreases in bone pain and no deterioration in performance status and quality of life. Pamidronate was tolerated well. CONCLUSIONS Monthly infusions of pamidronate provide significant protection against skeletal complications and improve the quality of life of patients with stage III multiple myeloma.

Efficacy of pamidronate in reducing skeletal complications in patients with breast cancer and lytic bone metastases

BACKGROUND Bisphosphonates such as pamidronate disodium inhibit osteoclast-induced bone resorption associated with cancer that has metastasized to bone. METHODS Women with stage IV breast cancer who were receiving cytotoxic chemotherapy and had at least one lytic bone lesion were given either placebo or pamidronate (90 mg) as a two-hour intravenous infusion monthly for 12 cycles. Skeletal complications, including pathologic fractures, the need for radiation to bone or bone surgery, spinal cord compression, and hypercalcemia (a serum calcium concentration above 12 mg per deciliter [3.0 mmol per liter] or elevated to any degree and requiring treatment), were assessed monthly. Bone pain, use of analgesic drugs, performance status, and quality of life were assessed throughout the trial. RESULTS The efficacy of treatment was evaluated in 380 of 382 randomized patients, 185 receiving pamidronate and 195 receiving placebo. The median time to the occurrence of the first skeletal complication was greater in the pamidronate group than in the placebo group (13.1 vs. 7.0 months, P=0.005), and the proportion of patients in whom any skeletal complication occurred was lower (43 percent vs. 56 percent, P = 0.008). There was significantly less increase in bone pain (P=0.046) and deterioration of performance status (P=0.027) in the pamidronate group than in the placebo group. Pamidronate was well tolerated. CONCLUSIONS Monthly infusions of pamidronate as a supplement to chemotherapy can protect against skeletal complications in women with stage IV breast cancer who have osteolytic bone metastases.

Long-term pamidronate treatment of advanced multiple myeloma patients reduces skeletal events. Myeloma Aredia Study Group.

PURPOSE To determine the efficacy and safety of 21 monthly cycles of pamidronate therapy in patients with advanced multiple myeloma. PATIENTS AND METHODS Patients with stage III myeloma and at least one lytic lesion received either placebo or pamidronate 90 mg intravenously administered as a 4-hour infusion monthly for 21 cycles. At study entry, the patients were stratified according to whether they were to receive first-line (stratum 1) or second-line (stratum 2) antimyeloma chemotherapy. Skeletal events (pathologic fracture, radiation or surgery to bone, and spinal cord compression) and hypercalcemia were assessed monthly. RESULTS The results of the first nine previously reported cycles are extended to 21 cycles. Of the 392 randomized patients, efficacy could be evaluated in 198 who received pamidronate and 179 who received placebo. After 21 cycles, the proportion of patients who developed any skeletal event was lower in the pamidronate-group (P = .015). The mean number of skeletal events per year was less in the pamidronate-group (1.3) than in placebo-treated patients (2.2; P = .008). Although survival was not different between the pamidronate-treated group and placebo patients overall, stratum 2 patients who received pamidronate lived longer than those who received placebo (14 v 21 months, P = .041). Pamidronate was safe and well tolerated during the 21 cycles of therapy. CONCLUSION Long-term monthly infusions of pamidronate as an adjunct to chemotherapy are superior to chemotherapy alone in reducing skeletal events in stage III multiple myeloma patients, and may improve the survival of patients on salvage therapy.

Long-term prevention of skeletal complications of metastatic breast cancer with pamidronate. Protocol 19 Aredia Breast Cancer Study Group.

PURPOSE Pamidronate, an aminobisphosphonate, has been shown to lower the risk of skeletal complications associated with lytic bone lesions for up to 1 year in women with stage IV breast cancer who received chemotherapy. We studied the long-term effectiveness and safety of continued treatment with intravenous pamidronate infusions for up to 2 years. PATIENTS AND METHODS Three hundred eighty-two women with metastatic breast cancer and lytic bone lesions who received chemotherapy were randomly assigned to receive either 90 mg of pamidronate or placebo intravenously every 3 to 4 weeks in this double-blind, multicenter, parallel-group trial. Patients were evaluated monthly for 2 years for skeletal complications, which included pathologic fractures, need for radiation or surgery to treat bone complications, spinal cord compression, and hypercalcemia. Bone pain, analgesic use, bone biochemical markers, performance status, quality of life, radiologic response in bone, and survival were also evaluated. RESULTS As in the first year of treatment, the proportion of patients with any skeletal complication was significantly less for the pamidronate than the placebo group at 15, 18, 21, and 24 months (P < .001). The proportions of patients with any pathologic fracture (i.e., vertebral and nonvertebral fractures), need for radiation or surgery to treat bone complications, and hypercalcemia were also statistically less for the pamidronate than the placebo group. The median time to the first skeletal complication was 13.9 months in the pamidronate-treated women and 7.0 months in the placebo group (P < .001). Long-term treatment did not result in any unexpected adverse events. Survival did not differ between the two groups. CONCLUSION The risk for osteolytic bone lesion complications in metastatic breast cancer was significantly decreased with monthly infusions of 90 mg of pamidronate, and this effect was maintained for at least 2 years. Pamidronate is a useful adjunct to standard chemotherapy in the palliative treatment of metastatic breast cancer.

Pamidronate Reduces Skeletal Morbidity in Women With Advanced Breast Cancer and Lytic Bone Lesions: A Randomized, Placebo-Controlled Trial

PURPOSE To assess whether pamidronate can reduce the frequency of skeletal morbidity in women with lytic bone metastases from breast cancer treated with hormone therapy. PATIENTS AND METHODS Three hundred seventy-two women with breast cancer who had at least one lytic bone lesion and who were receiving hormonal therapy were randomized to receive 90 mg of pamidronate or placebo as a 2-hour intravenous infusion given in double-blind fashion every 4 weeks for 24 cycles. Patients were evaluated for skeletal complications: pathologic fractures, spinal cord compression, irradiation of or surgery on bone, or hypercalcemia. The skeletal morbidity rate (the ratio of the number of skeletal complications to the time on trial) was the primary efficacy variable. Bone pain, use of analgesics, quality of life, performance status, bone tumor response, and biochemical parameters were also evaluated. RESULTS One hundred eighty-two patients who received pamidronate and 189 who received placebo were assessable. The skeletal morbidity rate was significantly reduced at 12, 18, and 24 cycles in patients treated with 90 mg of pamidronate (P = .028, .023, and .008, respectively). At 24 cycles, the proportion of patients having had any skeletal complication was 56% in the pamidronate group and 67% in the placebo group (P = .027). The time to the first skeletal complication was longer for patients receiving pamidronate than for those given placebo (P = .049). There was no statistical difference in survival or in objective bone response rate. Pamidronate was well tolerated. CONCLUSION Treatment with 90 mg of pamidronate as a 2-hour intravenous infusion every 4 weeks in addition to hormonal therapy significantly reduces skeletal morbidity from osteolytic metastases.

Pamidronate prevents skeletal complications and is effective palliative treatment in women with breast carcinoma and osteolytic bone metastases

Pamidronate therapy previously has been shown to reduce skeletal complications effectively for up to 12 months in breast carcinoma patients with bone metastases. The current study data provide further follow‐up results regarding the effects of long term (up to 24 months) pamidronate treatment in women with breast carcinoma and osteolytic metastases.

Objective evaluation of ampullary stenosis with ultrasonography and pancreatic stimulation

Ultrasonography can detect changes in pancreatic and bile duct sizes after pancreatic stimulation by secretin or morphine and prostigmine. The effects of the two pharmacologic regimens on pancreatic duct dilatation were comparable and correlated with papillary stenosis determined at surgery, but the morphine and prostigmine combination produced more false-positive responses than did secretin. After administration of intravenous secretin (1 unit/kg), the pancreatic duct dilated in 83 percent of 12 symptomatic patients found at surgery to have a stenotic sphincter of Oddi and in 72 percent of 17 symptomatic patients found to have a stenotic accessory papilla associated with the pancreas divisum anomaly. Comparable dilatation occurred in 14 percent of 14 control subjects without suspected ampullary disease and in none of 10 patients with surgically disproved stenosis (p less than 0.001). The morphine and prostigmine combination produced more false-positive results in both the pancreatic duct and bile duct. Concomitant elevation of the serum amylase level and reproduction of pain were found to be of no discriminatory value. In patients whose pancreatic duct dilated preoperatively during secretin stimulation, dilatation did not occur after surgical sphincteroplasty. A positive test result was associated with a 90 percent success rate in preventing recurrent pancreatitis and ameliorating pain. A negative test result was associated with a 29 percent success rate. Ultrasonography of the pancreatic duct with secretin stimulation may provide objective criteria to supplement clinical judgment in selecting patients for sphincteroplasty to treat stenosis of either the sphincter of Oddi or the accessory papilla in pancreas divisum.

Traumatic disruption of the thoracic aorta: significance of the left apical extrapleural cap

The plain chest film may be critical in deciding whether a seriously injured patient should undergo aortography in order to exclude traumatic aortic rupture. The roentgen findings suggestive of aortic transection reflect the presence of mediastinal bleeding. A left apical extrapleural cap is frequently seen in these patients but heretofore has not been emphasized in the literature.

Clinical use of a nonferromagnetic needle for magnetic resonance-guided biopsy

Five patients who had liver lesions detected by magnetic resonance (MR) and/or computed tomography (CT) were biopsied using MR guidance with a specially designed nonferromagnetic needle. The 20-gauge needle was constructed from Type 316 stainless steel in order to maximize needle visibility and minimize needle-tip artifact. In all cases adequate tissue was obtained for diagnosis and no side effects were observed during the biopsy or on clinical follow-up despite the fact that the needle was within the patient in MR for an average of 30 min.

Diagnostic Decision: Fine-Needle Transhepatic Cholangiography: Indications and Usefulness

: Fine-needle transhepatic cholangiography is a diagnostic tool often used for evaluating the biliary tree because of its wide availability and relatively low complication rate. Fine-needle cholangiography is primarily used in patients with obstructive jaundice with dilated ducts, but has been useful in patients with those entities that cause obstruction without dilatation (sclerosing cholangitis, ampullary stenosis, nonobstructing stone). We review our experience with over 700 cases of fine-needle cholangiography. The complication rate (due to bleeding, peritonitis, sepsis, and death) is less than 5%. The central role that fine-needle cholangiography plays in defining the site and cause of biliary obstruction is emphasized.