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Supportive Care
• Quadramet®
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Quadramet® (Samarium Sm-153 lexidronam, Cytogen) is a radiopharmaceutical used to manage pain in myeloma. It is currently approved in the US for relieving bone pain in patients who have confirmed metastatic bone lesions that are characterized by excessive bone formation and are visible on a bone scan, as is sometimes the case in myeloma. The scientific name of the drug is 153Sm-EDTMP.
Quadramet is different from other pain relievers. It pairs the targeting ability of a chemical that attaches to bone (EDTMP) with the therapeutic potential of radiation (radioactive samarium). This combination has a short radioactive half-life and targets areas of rapid bone turnover, such as those that occur in cancers that metastasize to the bone (ie, prostate, breast, and others) and in myeloma. The radiation selectively concentrates in these areas of the bone, reducing the exposure of normal organs and soft tissues outside the bone. Quadramet has been shown to relieve pain in patients with cancers that metastasize to the bone and may allow reduction or elimination of other pain medications.
Quadramet is administered intravenously over a 1-minute period, typically as an outpatient procedure. Pain relief may be apparent within 1 week but is maximal 3 to 4 weeks after injection and lasts 12 to 16 weeks. Patients usually benefit from a single injection, but they may receive additional doses of Quadramet if they begin to experience pain again.
The most common side effect seen with Quadramet therapy is myelosuppression (decrease in white blood cells and platelets), which is generally mild and transient, but may increase the risk of infectious and bleeding events. Some patients (about 5% to 10%) may experience a temporary increase in bone pain (pain flare) within a few days after beginning Quadramet therapy.
Patients should drink at least 2 cups of liquids before they will be receiving Quadramet to protect their bladder from the radioactive ingredient of the agent. The active ingredient in Quadramet is cleared from the body within about 12 hours. Therefore, patients must take some basic steps for 1 to 2 days afterward to protect themselves and others.
Quadramet is being further investigated alone and in combination with other therapies specifically in myeloma for its effects on pain relief and the disease process. Results of a small pilot study evaluating the combination of standard-dose Quadramet and the bisphosphonate zoledronic acid (Zometa®, Novartis) in elderly patients with symptomatic, chemotherapy-refractory myeloma were reported at the American Society of Clinical Oncology (ASCO) meeting in 2004. (Iuliano et al, J Clin Oncol. 2004;22(14S). Abstract 6737.) The combination provided significant pain relief in the 8 patients treated. Interestingly, levels of M-protein decreased more than 25% in half of the patients. Two patients experienced transient Grade 2 hematologic toxicity.
A Phase I/II trial is being conducted at the Mayo Clinic to confirm these results. The study will evaluate the use of Quadramet in combination with bisphosphonates for the treatment of pain associated with metastatic bone disease in patients with recurrent or refractory myeloma. The escalating dose clinical study will evaluate the drug's safety profile and effects on painful symptoms and analgesic use. In addition, preliminary information regarding the effect of Quadramet on the underlying disease will be determined by monitoring levels of M-protein, a marker for myeloma activity.
Quadramet is also being investigated at higher doses for use in conjunction with high-dose chemotherapy and stem cell transplantation to see if it can increase the efficacy of stem cell transplantation as a treatment for myeloma. In addition, it is being evaluated as part of combination therapy with Velcade® (bortezomib, Millennium) as a radiosensitizing agent in patients with relapsed or refractory myeloma.
Find out more about this investigational use of Quadramet in myeloma.
Quadramet is different from other pain relievers. It pairs the targeting ability of a chemical that attaches to bone (EDTMP) with the therapeutic potential of radiation (radioactive samarium). This combination has a short radioactive half-life and targets areas of rapid bone turnover, such as those that occur in cancers that metastasize to the bone (ie, prostate, breast, and others) and in myeloma. The radiation selectively concentrates in these areas of the bone, reducing the exposure of normal organs and soft tissues outside the bone. Quadramet has been shown to relieve pain in patients with cancers that metastasize to the bone and may allow reduction or elimination of other pain medications.
Quadramet is administered intravenously over a 1-minute period, typically as an outpatient procedure. Pain relief may be apparent within 1 week but is maximal 3 to 4 weeks after injection and lasts 12 to 16 weeks. Patients usually benefit from a single injection, but they may receive additional doses of Quadramet if they begin to experience pain again.
The most common side effect seen with Quadramet therapy is myelosuppression (decrease in white blood cells and platelets), which is generally mild and transient, but may increase the risk of infectious and bleeding events. Some patients (about 5% to 10%) may experience a temporary increase in bone pain (pain flare) within a few days after beginning Quadramet therapy.
Patients should drink at least 2 cups of liquids before they will be receiving Quadramet to protect their bladder from the radioactive ingredient of the agent. The active ingredient in Quadramet is cleared from the body within about 12 hours. Therefore, patients must take some basic steps for 1 to 2 days afterward to protect themselves and others.
Quadramet is being further investigated alone and in combination with other therapies specifically in myeloma for its effects on pain relief and the disease process. Results of a small pilot study evaluating the combination of standard-dose Quadramet and the bisphosphonate zoledronic acid (Zometa®, Novartis) in elderly patients with symptomatic, chemotherapy-refractory myeloma were reported at the American Society of Clinical Oncology (ASCO) meeting in 2004. (Iuliano et al, J Clin Oncol. 2004;22(14S). Abstract 6737.) The combination provided significant pain relief in the 8 patients treated. Interestingly, levels of M-protein decreased more than 25% in half of the patients. Two patients experienced transient Grade 2 hematologic toxicity.
A Phase I/II trial is being conducted at the Mayo Clinic to confirm these results. The study will evaluate the use of Quadramet in combination with bisphosphonates for the treatment of pain associated with metastatic bone disease in patients with recurrent or refractory myeloma. The escalating dose clinical study will evaluate the drug's safety profile and effects on painful symptoms and analgesic use. In addition, preliminary information regarding the effect of Quadramet on the underlying disease will be determined by monitoring levels of M-protein, a marker for myeloma activity.
Quadramet is also being investigated at higher doses for use in conjunction with high-dose chemotherapy and stem cell transplantation to see if it can increase the efficacy of stem cell transplantation as a treatment for myeloma. In addition, it is being evaluated as part of combination therapy with Velcade® (bortezomib, Millennium) as a radiosensitizing agent in patients with relapsed or refractory myeloma.
Find out more about this investigational use of Quadramet in myeloma.
Reviewed by:
William I. Bensinger, MD
Member, Fred Hutchinson Cancer Research Center
Professor of Medicine, University of Washington
10/24/06
William I. Bensinger, MD
Member, Fred Hutchinson Cancer Research Center
Professor of Medicine, University of Washington
10/24/06