Quadramet gives pain relief of bone metastases
Study shows increased survival rates
A single dose of Quadramet (samarium Sm 153 lexidronam injection) can offer significant relief for cancer patients suffering from painful bone metastases, according to a study published recently in the European Journal of Cancer (Vol. 33, pp. 1,583-1,591, 1997). The drug also prolonged the survival of some breast cancer patients in the seven-site European study.
Quadramet, from Princeton, NJ-based Cytogen Corp., was approved in March by the Rockville, MD-based Food and Drug Administration for the relief of pain in patients with confirmed osteoblastic metastatic bone lesions that enhance on radionuclide bone scan. This type of pain is most often experienced by patients with prostate, breast, or lung cancers. Quadramet, which is administered intravenously, was shown to be the first therapeutic radiopharmaceutical to have a statistically significant dose response for pain relief.
"If you go through the literature for this class of compounds, you can find articles that say there is no distinctive dose response for this class of drugs, but here we’ve found one," says Bill Goeckeler, PhD, director of pharmaceutical development for Cytogen Corp. "No one had ever seen a dose response before. We’re different from other drugs in the category because we normalize the dose based on the patient’s weight. It’s important because you like to know you’re giving the right dose. Without this study, you don’t know if giving more would be helpful or if a certain dose is enough."
Pain assessment conducted
In the study, 114 cancer patients with painful bone metastases the majority of whom had enough pain that they were already on other pain medications randomly received a single Quadramet dose of either 0.5 mCi/kg or 1.0 mCi/kg. During the first four weeks after administration, patients did a daily assessment of pain intensity, daytime discomfort, and quality of sleep. By week two, half of the patients in each dose group were experiencing some degree of pain relief. During the fourth week, which was the primary efficacy timepoint of the study, patients who received the higher dose showed statistically significant improvement in pain, daytime discomfort, and sleep. Seventy percent of the higher dose group showed pain relief by week four, compared with 55% in the lower dose group.
A predictable level of dose-related bone marrow suppression was seen in the study, Goeckeler says. Although the toxicity is mild compared with chemotherapy, patients who are undergoing other therapies that suppress bone marrow should not be given Quadramet at the same time. Platelet and white blood cell counts reached low points three or four weeks after administration with both doses but recovered to normal levels by the fifth week. Even at their lowest, the counts were generally higher than those commonly associated with serious complications.
An interesting result, though not the endpoint of the study, was increased survival rates in breast cancer patients, Goeckeler says. Because women with breast cancer generally receive more marrow-suppressive therapy than patients with other types of cancer that metastasize to bone, the researchers studied efficacy and safety of the drug in subgroups of patients based on sex and primary cancer. Female patients, particularly those with breast cancer, showed greater response to Quadramet at week four than the entire group of patients as well as male patients and men with prostate cancer. The 20 breast cancer patients who received the higher dose survived, on average, one year longer than the 16 breast cancer patients who received the lower dose. No similar survival difference was seen among the prostate cancer patients.
[For more information on Quadramet, contact: Bill Goeckeler, PhD, director of pharmaceutical development, Cytogen Corp., 600 College Road East CN 5308, Princeton, NJ 08540-5308. Telephone: (609) 987-8200. For product information, contact Dupont Merck at (800) 635-2683.]
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