wherein patients with DTC positive bone marrow had an approximately twofold increased risk of death versus DTC negative patients . Similarly, a recent study showed Erlotinib that detection of DTCs in patients with early breast cancer correlated with reduced distant metastasis free survival and reduced overall survival . Furthermore, at a median follow up of 56 months in these patients, DTC status was the only significant prognostic factor for locoregional Ofloxacin 82419-36-1 recurrence free survival in a multivariate analysis . These data suggest that DTC status in EBC correlates with risk of distant metastasis, locoregional recurrence, and death . Moreover, in a recent study , chemotherapy did not effectively eradicate DTCs in EBC patients . Bone marrow DTCs persisted in 36% of patients despite complete response to primary therapy .
buy glucitol Therefore, alternative therapeutic options that improve elimination of DTCs may reduce the risk of recurrence and improve survival in EBC. Recently, zoledronic acid significantly prolonged disease free survival and relapse free survival versus no ZOL or delayed use of ZOL in EBC patients undergoing adjuvant hormonal therapy in ABCSG 12 and ZO FAST . A possible underlying mechanism of action is that ZOL reduced disease recurrence by suppressing/eliminating DTCs. Indeed, Aft demonstrated that DTC free BC patients treated with ZOL were more likely to remain DTC free at 3 months and that the subset of patients with estrogen receptor negative and epidermal growth factor receptor 2 negative disease were more likely to have pathologic complete response with ZOL versus no ZOL.
In small studies, ZOL increased the proportion of DTC free patients who remained DTC free at 6 months versus no ZOL and significantly decreased DTC levels versus baseline at 12 and 24 months in DTC positive BC patients. purchase Fesoterodine Therefore, it is reasonable to hypothesize that ZOL may delay disease recurrence. However, the effects of ZOL on DTCs had not been evaluated in a randomized controlled study. Bone marrow aspirates for DTC assessment were obtained at baseline, 12 months, and 24 months after initiating study. After baseline and treatment initiation visits, eight additional study visits at 3 month intervals were planned. Clinical assessments at each visit included serum biochemistry, hematology, Eastern Cooperative Oncology Group performance status, and physical examination.
There was continuous adverse event monitoring and follow up scans for skeletal and nonskeletal lesions as clinically indicated. Patients were assessed using X rays, magnetic resonance imaging, or computed tomography scans for suspected bone metastases. Serum creatinine red blood cells was monitored before each ZOL infusion. Assessments of DTCs were conducted as previously described . For the quantitation of DTCs, 2 · 106 cells were analyzed on two slides per patient. Slides were automatically scanned using the ACIS imaging system , as described elsewhere . Criteria for detection of DTCs were based on European ISHAGE Working Group recommendations . Slides were centrally evaluated by two independent blinded observers. Nonconcordant results were evaluated by a third investigator.No formal hypothesis was tested for statistical significance; thus, the sample size of this trial was determined by feasibility considerations. The safety population included all patients who received at least one dose of study medication and all patients in the control group. Efficacy analysis was performed on the modified.