General Information

Quadramet (Samarium Sm 153 Lexidronam Injection) is a therapeutic agent consisting of radioactive samarium and a tetraphosphonate chelator.

Quadramet indicated for relief of pain in patients with confirmed osteoblastic metastatic bone lesions that enhance on radionuclide bone scan.

Quadramet is supplied as an intravenous injection. The recommended dose is 1.0 mCi/kg, administered intravenously over a period of one minute through a secure in-dwelling catheter and followed with a saline flush. Dose adjustment in patients at the extremes of weight have not been studied.

Caution should be exercised when determining the dose in very thin or very obese patients.

The dose should be measured by a suitable radioactivity calibration system, such as a radioisotope dose calibrator, immediately before administration. The dose of radioactivity to be administered and the patient should be verified before administering Quadramet. Patients should not be released until their radioactivity levels and exposure rates comply with federal and local regulations. The patient should ingest (or receive by i.v. administration) a minimum of 500 mL (2 cups) of fluids prior to injection and should void as often as possible after injection to minimize radiation exposure to the bladder.

Quadramet contains calcium and may be incompatible with solutions that contain molecules that can complex with and form calcium precipitates.

Quadramet should not be diluted or mixed with other solutions.

Mechanism of Action

Quadramet (samarium Sm-153 EDTMP) has an affinity for bone and concentrates in areas of bone turnover in association with hydroxyapatite. In clinical studies employing planar imaging techniques, more Quadramet accumulates in osteoblastic lesions than in normal bone with a lesion-to-normal bone ratio of approximately 5. The mechanism of action of Quadramet in relieving the pain of bone metastases is not known

Clinical Trial Results

Overall Quadramet was evaluated in 580 patients. Of these patients, 270 (244 men, 26 women) were studied in two randomized, blinded, placebo controlled clinical trials. These patients had a mean age of 67, and a range 22 to 87 years. Eligible patients had painful metastatic bone lesions that had failed other treatments, had at least a 6 month expected survival and had a positive radionuclide bone scan. Routine x-rays to evaluate the metastatic lesions were not part of the protocol. In study A, 118 patients were randomized to receive 0.5 mCi/kg Quadramet , 1.0 mCi/kg Quadramet , or a placebo intravenous injection. In study B, 152 patients were randomized to receive either 1.0 mCi/kg Quadramet or a placebo intravenous injection. Both studies were double blind over a 4 week period. Patients scored their daily pain intensity on a visual analogue scale rated from 0 (no or low pain) to 10 (excruciating pain). The area under the pain curve (AUPC) was obtained by integrating the daily pain scores by week. Opioid analgesic use was recorded daily and averaged over each week and expressed in oral morphine milligram equivalents. Of the 270 patients studied, 232 (86%) had prostate cancer and 38 (14%) had other primary cancers. In study A, 80 (68%) of the patients had prostate cancer and 38 (32%) had a variety of other primary tumors. In study B, all (100%) patients had prostate cancer. In both trials for each of the 4 weeks of study, the mean AUPC scores decreased in patients who received Quadramet (1.0 mCi/kg). In study A, pain (the AUPC) decrease from baseline was significantly different in Quadramet 1.0 mCi/kg and placebo groups at weeks 3 and 4. In study B, pain (the AUPC) decrease from baseline was significantly different in Quadramet 1.0 mCi/kg and placebo groups at weeks 2, 3 and 4.