The American Society of Clinical Oncology (ASCO) has developed updated guideline recommendations on the use of bisphosphonates, medications that help strengthen the bone, in people with multiple myeloma. The new guideline will be published in the June 10 issue of the Journal of Clinical Oncology.

The key recommendations in the guideline address:

В· Therapy duration, dosage and monitoring
В· Osteonecrosis of the jaw
В· Previous recommendations for solitary plasmacytoma, indolent myeloma, smoldering myeloma, monoclonal gammopathy and biochemical markers

Myeloma is a cancer caused by abnormal plasma cells that form tumors in the bone marrow. Myeloma can cause organ damage and increased breakdown and loss of bone, which can lead to pain, loss of bone structure, fractures and hypercalcemia. Over ninety percent of people with myeloma have more than one tumor, so the disease is often called multiple myeloma.

Patients who receive bisphosphonates when being treated for multiple myeloma may experience less bone pain, fewer fractures and slower loss of bone mass. Risks of bisphosphonate use include reduced kidney function, acute kidney failure and osteonecrosis of the jaw. The U.S. Food and Drug Administration (FDA) has approved two intravenous bisphosphonates for treating bone loss from multiple myeloma: pamidronate (Aredia) and zoledronic acid (Zometa).

Therapy Duration, Dosage and Monitoring

The guideline recommends that bisphosphonates be given to patients monthly for two years. At two years, the physician should consider stopping the use of bisphosphonates if the patient has responded to therapy. Physicians should re-start bisphosphonate therapy if a patient’s myeloma returns and new bone problems develop.

The guideline recommends that people with multiple myeloma who experience bone loss or fracture of the spine from osteopenia receive either 90 mg of pamidronate over two hours or 4 mg of zoledronic acid over at least 15 minutes, every three to four weeks.

The guideline recommends monitoring multiple myeloma patients receiving bisphosphonate therapy every three to six months for albuminuria-high levels of the protein albumin in the urine might indicate damage to the kidneys. According to FDA-approved labels of pamidronate and zoledronic acid, the physician also should monitor levels of creatinine, a chemical in the body used to measure kidney function, before providing a dose of either drug.

Physicians should stop administering pamidronate and zoledronic acid to patients who develop kidney problems while on either bisphosphonate,” said Kenneth C. Anderson, MD, co-lead author of the guideline and director of the Jerome Lipper Multiple Myeloma Center at the Dana-Farber Cancer Institute in Boston. “Treatment may be resumed once the exact kidney problem is identified and resolved.”

For multiple myeloma patients with existing kidney problems and extensive bone disease, the guideline does not recommend use of zoledronic acid. For these patients, the guideline recommends a longer infusion of four to six hours of pamidronate, instead of a two-hour infusion.

The guideline also recommends lowering the dose of pamidronate in multiple myeloma patients with pre-existing mild to moderate kidney disease. The manufacturer of Zometa previously recommended lowering the treatment dose for these patients as well.

Osteonecrosis of the jaw

The guideline includes new recommendations for patients with osteonecrosis of the jaw, or bone loss or deterioration of the jaw that occurs in some patients using bisphosphonates. Symptoms include infection of the jaw, pain, swelling, loose teeth and exposed bone.

The guideline recommends that all multiple myeloma patients receive a comprehensive dental examination and appropriate preventive dentistry prior to starting bisphosphonate therapy. All oral infections and areas in the mouth at high risk for infection should be treated,” said Robert A. Kyle, MD, co-lead author of the guideline and a hematologist at the Mayo Clinic in Rochester, Minn. Patients should maintain excellent oral hygiene and avoid invasive dental procedures, if possible, while receiving bisphosphonate therapy.”

Previous recommendations

The guideline update does not recommend use of bisphosphonates for myeloma patients with the following conditions:

В· One bone tumor (solitary plasmacytoma)
В· A slower growing form of myeloma (smoldering or indolent myeloma)
В· Conditions of abnormal plasma cells that are not myeloma but may eventually develop into myeloma (Monoclonal gammopathy of undetermined significance)

Additionally, the guideline does not suggest use of the biochemical markers to monitor bisphosphonate treatment for routine care of multiple myeloma patients.
Along with the new guideline, ASCO also has released a corresponding patient guide available on ASCO’s patient Web site, People Living With Cancer, at
“American Society Of Clinical Oncology 2007 Clinical Practice Guideline Update On The Role Of Bisphosphonates In Multiple Myeloma” by Robert A. Kyle, et al., Mayo Clinic, Rochester, Minn.

This guideline is being published in the June 10 print issue of the Journal of Clinical Oncology (JCO), the semi-monthly peer-reviewed journal of the American Society of Clinical Oncology (ASCO), the world’s leading professional society representing physicians who treat people with cancer.

For a copy of the guideline and available supplemental materials, visit www.asco/guidelines

The American Society of Clinical Oncology (ASCO) is the world’s leading professional organization representing physicians of all oncology subspecialties who care for people with cancer. ASCO’s nearly 25,000 members from the United States and abroad set the standard for patient care and lead the efforts to discover more effective cancer treatments, increase funding for clinical and translational research, and, ultimately, improve cancer care for the estimated 10 million people diagnosed with cancer worldwide each year. ASCO publishes the Journal of Clinical Oncology (JCO), the preeminent, peer-reviewed, medical journal on clinical cancer research, and produces People Living With Cancer (www.PLWC), a comprehensive consumer Web site providing oncologist-vetted cancer information to help patients and families make informed health-care decisions.

www.asco

View drug information on Aredia; Zometa.