mained DTC-positive at 12 months. DTC, disseminated zoledronic acid. suggesting effective DTC elimination by ZOL, although 24-month data were limited. In the recent report by Aft , chemotherapy alone also was not as effective as chemotherapy with concomitant ZOL for maintaining DTC-negative status. Moreover, chemotherapy alone had no discernible effect Lenalidomide on DTC status in DTC-positive patients. The enhanced reduction of DTCs with ZOL may be the result of anticancer effects of ZOL or anticancer synergy between ZOL and agents used for adjuvant therapy. Indeed, preclinical and clinical data have provided evidence of antitumor synergy between chemotherapeutic agents and ZOL.
Regardless of the mechanistic basis for the reduction/elimination of DTCs, it may be speculated that the reduction of DTCs by ZOL treatment may, in part, contribute to the significant Piperine inhibitor improvements in DFS with ZOL Elvitegravir 697761-98-1 reported in adjuvant clinical trials in EBC. Overall, treatment with ZOL was 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 meta. 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.
Moreover, ZOL-treated patients had numerically fewer locoregional and distant versus hormonal therapy alone. Furthermore, buy JNJ 26854165 at the 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 . 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 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 social roles to speculate that the potential anticancer benefit of ZOL may be mediated through reduction/elimination of DTCs, and ZOL treatment in conjunction with primary therapy may improve clinical benefits. It should be noted, however, that because of the small number of patients in the current study, these data may be considered as hypothesis generating. In the current study, the decision to measure bone marrow DTCs instead of the more easily measured circulating tumor cells in blood was guided by data suggesting that DTCs correlate strongly with disease outcomes. However, the requirement for bone marrow biopsies in patients without clinical evidence of residual disease was a major reason for patient withdrawal. This resulted in major limitations for this study, including a high proportion of missing values for the primary variable, insufficient statistical power, and potentially compromised randomization because of attrition of accrued patients. Additionally, the ACIS automated method utilized in the current study may be less sensitive than the MDS1 or manual .