The Mayo Clinic guidelines also recommend less frequent administration of bisphosphonates as maintenance in patients who after 2 years still have active myeloma or osteolytic bone disease. This recommendation, in part, reflects the sustained bone protection provided by bisphosphonates, Afatinib in contrast with more transient antiresorptive effects with other classes of bone targeted therapies . The National Comprehensive Cancer Network recommends the use of bisphosphonates in all patients with symptomatic disease receiving primary therapy and prefers ZOL for the treatment of hypercalcemia in this patient population . Recent advances in the management of cancer induced bone disease include the development of denosumab, a human IgG2 monoclonal antibody that binds to human RANKL .
In a Phase III, head to head trial comparing monthly denosumab versus ZOL Vincristine 2068-78-2 for a median of 7 months in patients with advanced solid tumors or MM , the time to first on study SRE in patients with MM was similar in each treatment group at 34 months . Denosumab did demonstrate a higher mortality rate compared with ZOL in patients with MM and is not currently approved for prevention of SREs in this patient population, although overall survival was similar between the two treatment groups for the total patient population . In this retrospective database analysis, the majority of patients received continuous ZOL treatment for <1 year. Patients with longer ZOL treatment durations consistently achieved better outcomes in terms of overall SREs and fractures.
Moreover, patients treated with ZOL had longer survival overall compared with the no bisphosphonate cohort. Among all patients included in the study, those who received ZOL for at least 1.5 years had the lowest risk of SREs and fracture. As expected, patients treated with ZOL had a significant reduction in the risk of SREs and death compared buy Fesoterodine with patients who did not receive therapy with an intravenous bisphosphonate . These results are consistent with recent analyses from the MRC Myeloma IX trial showing ongoing reductions in SREs and improved overall survival with ZOL versus clodronate during the course of treatment and maintenance therapy . In this trial, 1960 patients were randomized to intensive versus nonintensive treatment and further randomized within each treatment group to clodronate or ZOL with and without thalidomide until disease progression .
Overall, the risk of SREs purchase Bortezomib was reduced by 26% in the ZOL group versus the clodronate group . The reductions in SRE risk were shown regardless of bone lesions at baseline and within the first year of treatment. Furthermore, SREs continued to be decreased in the ZOL group neural plate versus the clodronate group after completing 2 years of treatment . The clinical benefit of uninterrupted treatment with ZOL in patients with MM is evident from these data. Prior to the current analysis and the recent reports from the MRC Myeloma IX trial, clinical evidence supporting the continued SRE reduction from long term bisphosphonate use in patients with MM was limited. A retrospective study involving 57 patients with either solid tumors or MM and treated with PAM and/or ZOL for a median duration of 34 months reported an overall low incidence of SREs; 26 patients experienced an SRE after starting bisphosphonate treatment, and the overall skeletal morbidity rate was 0.20 SREs per year .