Among the most common AEs associated with ZOL were arthralgia, myalgia, and pyrexia, reflecting the known flu like acute phase reaction that can occur, typically after the first infusion. Fatigue and neutropenia were most common in the control group . Most AEs in the ZOL group were grade 1 or 2. The most frequent grade 3 events were hematologic: grade 3 neutropenia Decitabine and grade 3 leukopenia . Only two patients in the ZOL arm and three patients in the control arm discontinued treatment because of an AE. There was one case of ONJ in a patient with completely normal dental health prior to developing ONJ 576 days after the start of study medication and lasting 207 days, necessitating prolonged hospitalization, the administration of concomitant medication, and nondrug therapy.
This patient also developed moderate osteomyelitis posaconazole 171228-49-2 lasting 27 days, which started 756 days after initiating study medication.generally well tolerated, and there were few treatment discontinuations because of AEs . The detection of DTCs correlates significantly with increased risks of visceral and bone metastasis, locoregional recurrence, and death in BC patients . Therefore, treatments that eliminate or reduce DTCs in bone marrow may potentially decrease risk of recurrent or metastatic disease and improve survival. Indeed, reduced risks of recurrent disease were reported in clinical trials exploring ZOL as adjuvant therapy in EBC patients. In ABCSG 12, the addition of ZOL to endocrine therapy for 3 years in younger women with early EBC and treatment induced menopause significantly improved DFS by 36% and recurrence free survival by 35% relative to no ZOL .
At a median follow up of 48 months, ZOL also produced a trend toward a 40% lower risk of death versus no ZOL . Moreover, ZOL treated patients had numerically fewer locoregional and distant recurrences and contralateral disease events versus hormonal therapy alone. Furthermore, at the buy Irinotecan 36 month analysis of ZO FAST in postmenopausal women receiving letrozole as adjuvant therapy for EBC, upfront use of ZOL significantly improved DFS by 41% versus using ZOL only after clinically relevant bone loss was detected . purchase dimebon Consistent DFS benefits were reported in an integrated analysis of ZO FAST and a similarly designed trial . Consistent with ABCSG 12, the upfront ZOL group had reduced rates of disease recurrence at both local and distant sites .
However, because bone marrow biopsies were not obtained, the effects of ZOL on DTCs in these studies are unknown. Furthermore, multivariate analysis of data from the AZURE study showed that the addition of monthly ZOL in the subset of patients receiving neoadjuvant chemotherapy for stage II/III BC significantly reduced residual invasive red blood cells tumor size and nearly doubled the rate of pathologic complete responses . In the recently reported mature results of the AZURE trial, although no benefit was reported in the overall study population, subset analyses showed that ZOL treatment significantly reduced the absolute risk of recurrent invasive disease by 7% and improved the 5 year survival rate by 6% in patients who had undergone menopause at least 5 years before study entry . These data are consistent with the observation of DTC reduction in postmenopausal women compared with no apparent reduction in mean DTC numbers in premenopausal women in the current study. Thus, it is tempting to speculate that the potential anticancer benefit of ZOL may be mediated through.