Background: Z prevents skeletal-related events (SREs) in pts with bone metastases or multiple myeloma. However, secondary hyperparathyroidism and increased PTH may stimulate osteoclast activity and tumor growth, thus potentially limiting the efficacy of Z. Methods: Serum PTH was assessed at baseline and every 3 months in 1,068 pts enrolled in 3 randomized trials: 547 received Z, and 521 received placebo or pamidronate. Results: 213 (20%) pts had elevated PTH at baseline, and 105 of 547 (19%) pts had elevated PTH during Z treatment. In patients with normal baseline PTH, Z significantly reduced the incidence of SREs and delayed time to first SRE compared with control, whereas the risk of SREs was not reduced in patients with elevated baseline PTH. In prostate cancer patients, Z significantly decreased the risk of death compared with placebo in pts with normal baseline PTH (relative risk [RR] = 0.72; 95% confidence interval [CI]: 0.55, 0.94; P = .015). No survival advantage was observed in this subpopulation among pts with lung cancer or other solid tumors. In the small subset of pts with elevated PTH during Z treatment, there was an increased risk of death (for breast cancer pts, RR = 1.68 [95% CI: 1.10, 2.56]; P = .016; for prostate cancer pts, RR = 2.92 [95% CI: 1.83, 4.67]; P < .001). Additionally, elevated PTH during Z treatment in prostate cancer pts also significantly correlated with an increased risk of bone lesion progression (RR = 1.54 [95% CI: 1.09, 2.17]; P = .015). Elevated PTH during treatment did not affect the incidence or time to onset of SREs. Among pts with lung cancer or other solid tumors, elevated PTH during Z treatment did not provide any predictive or prognostic information. Conclusions: PTH levels either at baseline or during Z treatment appear to correlate with disease progression and the clinical benefit of Z in pts with bone metastases from certain types of cancer. This retrospective analysis suggests the importance of PTH status in patients undergoing Z treatment. Normalization of PTH levels may increase the benefit of Z.
Effect of zoledronic acid (Z) treatment based on serum parathyroid hormone (PTH) levels in patients (pts) with malignant bone disease.
BERRUTI, Alfredo;DOGLIOTTI, Luigi;TAMPELLINI, MARCO;
2006-01-01
Abstract
Background: Z prevents skeletal-related events (SREs) in pts with bone metastases or multiple myeloma. However, secondary hyperparathyroidism and increased PTH may stimulate osteoclast activity and tumor growth, thus potentially limiting the efficacy of Z. Methods: Serum PTH was assessed at baseline and every 3 months in 1,068 pts enrolled in 3 randomized trials: 547 received Z, and 521 received placebo or pamidronate. Results: 213 (20%) pts had elevated PTH at baseline, and 105 of 547 (19%) pts had elevated PTH during Z treatment. In patients with normal baseline PTH, Z significantly reduced the incidence of SREs and delayed time to first SRE compared with control, whereas the risk of SREs was not reduced in patients with elevated baseline PTH. In prostate cancer patients, Z significantly decreased the risk of death compared with placebo in pts with normal baseline PTH (relative risk [RR] = 0.72; 95% confidence interval [CI]: 0.55, 0.94; P = .015). No survival advantage was observed in this subpopulation among pts with lung cancer or other solid tumors. In the small subset of pts with elevated PTH during Z treatment, there was an increased risk of death (for breast cancer pts, RR = 1.68 [95% CI: 1.10, 2.56]; P = .016; for prostate cancer pts, RR = 2.92 [95% CI: 1.83, 4.67]; P < .001). Additionally, elevated PTH during Z treatment in prostate cancer pts also significantly correlated with an increased risk of bone lesion progression (RR = 1.54 [95% CI: 1.09, 2.17]; P = .015). Elevated PTH during treatment did not affect the incidence or time to onset of SREs. Among pts with lung cancer or other solid tumors, elevated PTH during Z treatment did not provide any predictive or prognostic information. Conclusions: PTH levels either at baseline or during Z treatment appear to correlate with disease progression and the clinical benefit of Z in pts with bone metastases from certain types of cancer. This retrospective analysis suggests the importance of PTH status in patients undergoing Z treatment. Normalization of PTH levels may increase the benefit of Z.
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