in the present study, where the incidence of SREs in the ZOL treatment cohort was 20.40 events per 100 person years. In contrast, the ZOL registration trial, in which 1,648 patients with bone lesions from MM or breast cancer were treated with an intravenous bisphosphonate for 24 months, reported a higher incidence of SREs . Overall, patients treated with ZOL experienced 1.0 Bosutinib event per year, and patients treated with PAM experienced 1.4 events per year. Because the present study focused only on patients with MM receiving ZOL, it is difficult to directly compare these studies. Moreover, the previous studies have not reported the risk of SREs by duration of bisphosphonate treatment. However, in the MRC Myeloma IX trial, the annual rates were 0.4 SREs/ patient for ZOL versus 0.
8 SREs/patient for clodronate, and between group differences in SRE rates were significant in each of Vinorelbine 71486-22-1 the first 6 years of the study . Survival improvement in patients with MM receiving ZOL has been reported in some previous studies, although the patient populations in those studies were exclusively untreated or newly diagnosed. In the MRC Myeloma IX trial, patients in the ZOL group had a 5.5 month longer median survival compared with the clodronate group , after a median follow up of 3.7 years . Furthermore, ZOL reduced the proportion of patients with SRE independently of the survival benefit, suggesting antimyeloma activity.
A randomized clinical study in 94 patients with untreated MM who received standard chemotherapy and were randomized to receive either concurrent ZOL or no ZOL demonstrated buy Cilostazol purchase Benazepril that both overall survival and event free survival were significantly higher among patients who received ZOL compared with patients who did not receive ZOL after a median follow up of 49.6 months . Whether the improved survival during ZOL treatment is a result of direct antimyeloma activity or a secondary effect through the bone microenvironment has not been determined. Preclinical research has demonstrated that ZOL may have direct anticancer activity . Moreover, subgroups of patients with MM may be more likely to derive benefit from ZOL versus other bisphosphonates based on gene expression profiles or specific myeloma–bone interactions . There are limitations that should be considered when interpreting the results of the present study.
First, the follow up time periods were different among the patient cohorts, neural plate which was not possible to completely control for in the analyses. Second, the small number of patients in the longer persistency categories may have reduced the power to identify a statistically significant risk reduction among the patients receiving long term ZOL. However, it is also possible that patients in the longer persistency categories had baseline clinical and demographic characteristics that placed them at lower risk for SREs and fractures and led to longer survival. In addition, front line treatments such as bortezomib, which may improve bone anabolism in MM, could influence outcomes during subsequent bisphosphonate treatment. In this study, a larger proportion of patients in the ZOL cohort received bortezomib than did patients in the No Bisphosphonate cohort. Finally, causality cannot be confirmed for the relationship between persistency and SRE rates. Patients were not randomly assigned to persistency cohorts, and it is likely that many patients’ shorter persistency was caused by their short survival or treatment discontinuation because of SREs.