Between 20% and 40% of lung cancer patients will have bone metastases, Dr. Nikos K. Karamanos, from the University of Patras, and colleagues note. Recent experimental evidence suggests that third generation bisphosphonates can block proliferation and induce apoptosis in a wide range of cancer cells, including those from both small and non-small-cell lung cancers.
The current study, reported in the International Journal of Cancer for October 1, featured 144 patients with stage IV lung cancer and evidence of metastases on bone scan. Of these patients, 87 had bone pain and received zoledronic acid, 4 mg IV every 21 days, while the remaining 57 did not receive the drug. All of the subjects were treated with docetaxel and carboplatin.
The median survival period for zoledronic acid users was 578 days, significantly longer than the 384 days achieved in the comparison group (p < 0.001). The corresponding median times to disease progression were 265 and 150 days (p < 0.001).
The researchers also found that as the number of zoledronic acid treatment cycles increased, so did the survival period and the time to disease progression (p < 0.01 for both).
By contrast, zoledronic acid use appeared to have no significant effect on bone pain, the report indicates.
Zoledronic acid use was also associated with a drop in urine levels of N-telo-peptide of type I collagen (NTx), an indicator of bone breakdown. However, this was only seen in patients who had levels no greater than 29 nM BCE/mM creatinine at baseline.
“The addition of bisphosphonates seems to increase overall survival in lung cancer patients with bone metastases, and the prolongation of (bisphosphonate) administration is correlated with longer survival and time to progression,” the authors conclude.
“Furthermore, initial NTx to creatinine ratios seem to have a negative correlation with time to progression and patient survival, whereas response to chemotherapy and survival is correlated with lower NTx to creatinine ratio levels.”
Int J Cancer 2009;125:1705-1709.