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Zoledronic Acid Slows Pain Progression, Reduces Bone Complications

CHICAGO, April 29 /PRNewswire-FirstCall/ -- ZOMETA® (zoledronic acid) Injection treatment of patients with prostate cancer that has spread to bone significantly lowers the risk of debilitating bone complications and delays their onset by a median time of more than five months. In addition, increases in pain scores were consistently lower for patients on ZOMETA than for those on placebo, according to data presented today during the annual meeting of the American Urological Association (AUA) in Chicago.

Research indicates that 65% to 75% of all patients with advanced prostate cancer develop bone metastasis, the spread of cancerous cells from the original tumor to bones. Often, bone is the only site of metastasis in these patients. Complications resulting from bone metastases include, among others, bone pain, pathologic fractures, a need for radiation or surgery to bone, spinal cord compression and hypercalcemia. These painful, debilitating complications can significantly impact the daily lives of patients and caregivers. A recently published analysis indicates that skeletal fractures in patients with prostate cancer can correlate with decreased survival. ZOMETA is the first and only bisphosphonate indicated for prostate-related bone metastases.

"The lives of patients with advanced prostate cancer and complications from bone metastases are often typified by severe pain and an inability to carry out daily activities," said Fred Saad, M.D., lead investigator and Associate Professor of Urology and Director of Urologic Oncology at the Montreal Cancer Institute, University of Montreal. "These findings demonstrate ZOMETA may reduce the risk of bone complications and their pain progression. The resulting improvement may reduce the stress and burden both patients and their caregivers experience on a daily basis."

Study Details Design

The multicenter, randomized, placebo-controlled trial was conducted in 643 patients with advanced prostate cancer and at least one site of bone metastasis. Of the 643 patients, 208 completed the 15-month core phase, and an additional 186 patients continued to receive double-blind study medication during an extension phase.

Bone Complications

After 24 months of treatment, only 38% of patients in the ZOMETA group had experienced a bone complication (also called a skeletal related event, or SRE). By contrast, 49% of patients in the placebo group (P=0.028) developed SREs.

In addition, when compared to placebo, ZOMETA significantly delayed the time to the first bone complication by more than five months (median, 488 days vs. 321 days for placebo, P=0.009) and time to the first pathologic fracture. ZOMETA also significantly reduced the skeletal morbidity rate (mean, 0.77 vs. 1.47 events/year for placebo, P=0.005). A skeletal morbidity rate is the ratio of the number of skeletal complications over a defined period time.

The study also included a multiple event analysis, which showed that ZOMETA reduced the overall risk of developing an SRE by 36% (hazard ratio= 0.64; 95% confidence interval [CI] 0.49; 0.85; P=0.002). This means that patients' risk of developing one or more complications, such as fractures, while on ZOMETA was significantly reduced.

Bone Pain

ZOMETA consistently reduced the rate of pain score increases over the entire 24 months that patients were in the study, as assessed by the Brief Pain Inventory (BPI) at baseline and at six-week intervals. This is the first demonstration of durable effect on bone pain achieved with bisphosphonate therapy in patients with prostate cancer metastatic to bone.

About ZOMETA

An intravenous bisphosphonate, ZOMETA is the first therapy of its kind to demonstrate efficacy in treating bone complications across a broad range of tumor types such as breast, prostate, lung and renal cell cancers. Prior to ZOMETA, bisphosphonates had only been used in multiple myeloma and breast cancer patients with bone metastasis. ZOMETA offers patients, nurses and clinicians a convenient 4 mg, 15-minute infusion time.

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 prostate, breast, lung, renal and colorectal cancer. ZOMETA also is indicated for the treatment of hypercalcemia of malignancy (HCM), the most common life-threatening metabolic complication of cancer.

Recently, Novartis submitted applications with the U.S. Food and Drug Administration (FDA) and the European Agency for Evaluation of Medicinal Products (EMEA) to include in its labeling data demonstrating the long-term benefit of ZOMETA for patients with bone metastases from advanced cancers. The filings report on approximately two years of treatment and safety data.

Contraindications and Adverse Events

In this study, the safety profile with ZOMETA was similar to that of other intravenous bisphosphonates. ZOMETA and other IV bisphosphonates have 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 dilutent.

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.

The foregoing release contains forward-looking statements that can be identified by terminology such as "reduces risk," "lowers risk," "delays onset," "will make," "reduces pain," or similar expressions, or by discussions regarding potential new indications for ZOMETA, or regarding potential future sales of ZOMETA. Such forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause actual results with ZOMETA to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that ZOMETA will be approved for any additional indications in any market. Neither can there be any guarantee regarding potential future sales of ZOMETA. In particular, management's ability to ensure satisfaction of the health authorities' further requirements is not guaranteed and management's expectations regarding commercialization of ZOMETA could be affected by, among other things, additional analysis of ZOMETA clinical data; new clinical data; unexpected clinical trial results; unexpected regulatory actions or delays or government regulation generally; the company's ability to obtain or maintain patent or other proprietary intellectual property protection; competition in general; and other risks and factors referred to in the company's current Form 20-F on file with the Securities and Exchange Commission of the United States. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those anticipated, believed, estimated or expected.

About Novartis

Novartis Oncology is a business unit within Novartis AG , a world leader in pharmaceuticals and consumer health. In 2002, the Group's businesses achieved sales of CHF 32.4 billion (USD 20.9 billion) and a net income of CHF 7.3 billion (USD 4.7 billion). The Group invested approximately CHF 4.3 billion (USD 2.8 billion) in R&D. Headquartered in Basel, Switzerland, Novartis Group companies employ about 72,900 people and operate in over 140 countries around the world. For further information please consult http://www.novartis.com.

Full prescribing information is available upon request.

Additional information can be found at http://www.us.zometa.com/, http://www.novartisoncology.com/ or http://www.novartisoncologyvpo.com/

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