Zoledronic Acid ( Zometa ), an intravenous bisphosphonate, was shown to inhibit aromatase inhibitor-induced bone loss in postmenopausal women treated with Letrozole ( Femara ) in the adjuvant breast cancer setting.

Final data of the primary endpoint of 12-month bone mineral density ( BMD ) demonstrate a significant increase in BMD for those breast cancer patients treated with Femara and upfront Zometa compared with those who received Femara and delayed Zometa.

Several studies have shown that women treated with hormonal therapy in the adjuvant breast cancer setting are at risk of bone loss.
New data from the Z- FAST ( Zometa-Femara Adjuvant Synergy Trial ) study offer evidence that Zometa may prevent bone loss in these patients.
These data are particularly important given that aromatase inhibitors are a widely prescribed hormonal therapy for newly diagnosed breast cancer.

The Z-FAST study showed that at the 12-month follow-up, the group of patients receiving upfront Zometa had a mean increase of lumbar spine BMD of 1.9% vs. a decrease of 2.4% in the group of patients who received delayed Zometa ( p<0.0001 ).
This represents a 4% relative difference in lumbar spine BMD in favor of the upfront Zometa group.
Total hip BMD was also significantly higher in the upfront group, compared to the delayed group.
Significantly, 8% of patients in the delayed group had decreases in BMD at the 12-month follow-up, which required initiation of Zometa.

Zometa is generally well tolerated in non-metastatic cancer patients.
The following adverse events occurred in more than 5% of patients in the Z-FAST study: arthralgia ( 30% in upfront group, 29% in delayed group ); hot flashes ( 25.3%, 25.7% ); fatigue ( 17.3%, 15.3% ); myalgia ( 12.7%, 9.7% ); bone pain ( 11.3%, 4% ); headache ( 9%, 7.3% ); nausea ( 8%, 5.7% ); pain in extremities ( 8%, 4.3% ); insomnia ( 7%, 5.3% ); depression ( 5.7%, 9% ) back pain ( 6%, 5.7% ).

The Z-FAST study is part of a wider clinical program that includes the international sister trial Zo-FAST.
Zo-FAST, which will include more than 900 patients in 30 countries outside the U.S., is investigating the same primary and secondary endpoints and will add to this body of clinical evidence.

Zometa was granted marketing authorization by the FDA in February 2002 for the treatment of bone complications in patients with advanced malignancies involving bone.
Zometa is indicated for the treatment of patients with multiple myeloma and patients with documented bone metastases from solid tumors, in conjunction with standard antineoplastic therapy.
In prostate cancer, patients should have progressed after treatment with at least one hormonal therapy.
The solid tumors studied included, among others, prostate, breast, lung, renal and colon. Zometa also is indicated for the treatment of hypercalcemia of malignancy ( HCM ), the most common life-threatening metabolic complication of cancer.

Zometa has been associated with reports of renal insufficiency. Patients should have serum creatinine assessed prior to receiving each dose of Zometa.
Caution is advised when Zometa is used in Aspirin sensitive patients, or with aminoglycosides, loop diuretics, and other potentially nephrotoxic drugs.
Due to the risk of clinically significant deterioration in renal function, single doses of Zometa should not exceed 4 mg and the duration of infusion should be no less than 15 minutes in 100 ml of diluent.

In clinical trials in patients with bone metastases and hypercalcemia of malignancy ( HCM ), Zometa had a safety profile similar to other intravenous bisphosphonates.
The most commonly reported adverse events included flu-like syndrome ( fever, arthralgias, myalgias, skeletal pain ), fatigue, gastrointestinal reactions, anemia, weakness, cough, dyspnea and edema.

Zometa should not be used during pregnancy.

Zometa is contraindicated in patients with clinically significant hypersensitivity to Zoledronic Acid or other bisphosphonates, or any of the excipients in the formulation of Zometa.

Osteonecrosis of the Jaw ( ONJ ) has been reported in patients with cancer receiving treatment including bisphosphonates, chemotherapy, and/or corticosteroids.
The majority of reported cases have been associated with dental procedures such as tooth extraction.
A dental examination with appropriate preventive dentistry should be considered prior to treatment with bisphosphonates in patients with concomitant risk factors.
While on treatment, these patients should avoid invasive dental procedures if possible.
No data are available as to whether discontinuation of bisphosphonate therapy reduces the risk of ONJ in patients requiring dental procedures.

Source: 41st Annual Meeting of the American Society of Clinical Oncology ( ASCO ), 2005


XagenaMedicine2005