The bisphosphonate zoledronic acid (Zometa) offers significant benefit in lowering the skeletal-related events rate in patients with bony metastatic bladder cancer, according to results of a prospective, randomized, placebo-controlled study.
Chicago-The bisphosphonate zoledronic acid (Zometa) offers significant benefit in lowering the skeletal-related events rate (SRE) in patients with bony metastatic bladder cancer, according to results of a prospective, randomized, placebo-controlled study.
In the study, by researchers from the National Cancer Institute and University of Cairo, Egypt, 40 patients were treated with palliative radiotherapy and randomized 1 week later to receive an IV infusion of zoledronic acid, 4 mg, dissolved in 250 mL of normal saline or the same volume of normal saline monthly for 6 months. The majority of patients had transitional cell carcinoma, and there were no significant differences in baseline features between the two treatment groups.
Analyses of results based on a median follow-up of 183 days (range, 58 to 756 days) showed statistically significant benefits of zoledronic acid treatment for decreasing the number of SREs, delaying their onset, and reducing SRE-related pain, as reported at the American Society of Clinical Oncology annual meeting. In addition, a trend was noted for treatment with zoledronic acid to improve 1-year overall survival, reported study co-author Rimoun Boutrus, MD, who was an attending physician at the National Cancer Institute in Cairo working with Mohamed S. Zaghloul, MD, when the study was conducted.
Skeletal events cut in half
In the randomized study, the mean number of SREs was reduced by more than half in patients treated with zoledronic acid compared with the control arm (0.9 vs. 2.05, respectively), and in a multiple event analysis, zoledronic acid significantly reduced the hazard of an SRE by 58%.
In addition, treatment with the bisphosphonate significantly delayed time to onset of the first SRE by twofold. The median time to the first SRE was 56 days in the control arm and 115 days in patients treated with zoledronic acid. Treatment with zoledronic acid was also associated with a significant reduction in mean pain score compared with the control group (2.95 vs. 4.37, respectively).
Based on Kaplan-Meier techniques, the 1-year overall survival rate was 30% among patients treated with zoledronic acid and 5% among controls. The difference between groups showed a trend toward statistical significance.
"At the time of initiation of the study, it was not powered to detect a difference in overall survival. However, we did observe a trend for improvement, which we believe is probably due to improvement in quality of life with zoledronic acid treatment," Dr. Boutrus told Urology Times.
"Zoledronic acid may have direct antitumor effects secondary to its pro-apoptotic activity. However, we believe the primary mechanism for any survival benefit associated with zoledronic acid relates to its effects on quality of life, considering the findings of a study reported in the Journal of Clinical Oncology [2003; 21:673-8], showing that improved quality of life was associated with improved overall survival in metastatic bladder cancer patients."
There were no significant differences between study groups in distant metastasis to nonskeletal sites, and the zoledronic acid infusion was generally safe and well tolerated. No patients developed generalized bony pain, gastrointestinal tract-related events, eye symptoms, or local reactions at the infusion site. Hypocalcemia developed in three patients in the zoledronic acid arm, and elevations in serum creatinine occurred in five zoledronic acid patients and in seven placebo patients.
David I. Quinn, MD, PhD, who discussed the research at the ASCO meeting, observed that the small study has limited power, but that the overwhelmingly positive results provide some basis for moving forward, and the researchers deserve international recognition for providing the best information available to date on outcomes of zoledronic acid treatment in patients with bony metastatic bladder cancer.
"The benefits observed in this study are consistent with those found in other cancer populations and in a small study from Germany reported last year," said Dr. Quinn, chief of genitourinary medical oncology at the University of Southern California, Los Angeles.
"Even though the Egyptian study was underpowered, it appears zoledronic acid probably has a place in the treatment of patients with urothelial cancer and bone metastases. However, there is some potential toxicity associated with zoledronic acid, particularly in patients with renal impairment, and so it is important to proceed with caution."