To evaluate the dose-response effect of an adjuvant anthracycline-based non-taxane chemotherapy in early breast cancer patients. This was a retrospective database analysis. Selection criteria included patients treated for early breast cancer from years 1980 to 2000 with an adjuvant anthracycline-based non-taxane chemotherapy. The delivery of chemotherapy was assessed through the number of delayed cycles, the number of delayed days and the relative dose intensity (RDI) administered (C85%, \85%). Seven hundred and ninety-three breast cancer patients were included. The Kaplan-Meier disease-free survival (DFS) was affected by the number of delayed cycles (P \ 0.0001), the number of delayed days (P \ 0.0001) and the RDI (P = 0.0029). The KaplanMeier overall survival (OS) was also affected by the number of delayed cycles (P = 0.0008) and days (P = 0.0115), as well as the RDI (P = 0.0055). The Cox regression models showed that, when the number of nodes affected and the hormonal receptor status were controlled, all the study variables maintained their significance on DFS, but not on OS. The dose-response effect is a crucial factor in the administration of anthracycline-based nontaxane schedules for the adjuvant treatment of early breast cancer. Delays and/or reductions of chemotherapy should be avoided if possible to achieve the maximal benefit.
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Background
Antiviral prophylaxis is recommended in cytomegalovirus (CMV)-seropositive kidney transplant (KT) recipients receiving antithymocyte globulin (ATG) as induction. An alternative strategy of premature discontinuation of prophylaxis after CMV-specific cell-mediated immunity (CMV-CMI) recovery (immunoguided prevention) has not been studied. The aim of this study was to evaluate whether it is effective and safe to discontinue prophylaxis when CMV-CMI is detected and to continue with preemptive therapy.
Methods
In this open-label, non-inferiority clinical trial, patients were randomized 1:1 to follow immunoguided strategy, receiving prophylaxis (valganciclovir 900 mg daily) until CMV-CMI recovery or to receive fixed-duration prophylaxis until day +90. After prophylaxis, preemptive therapy (valganciclovir 900 mg twice daily) was indicated in both arms until month 6. The primary and secondary outcomes were incidence of CMV disease and replication, respectively, within the first 12 months. Desirability of outcome ranking (DOOR) assessed two deleterious events (CMV disease/replication and neutropenia).
Results
A total of 150 CMV-seropositive KT recipients were randomly assigned. There was no difference in the incidence of CMV disease (0% vs. 2.7%; P = 0.149) and replication (17.1% vs. 13.5%; log-rank test, P = 0.422) between both arms. Incidence of neutropenia was lower in the immunoguided arm (9.2% vs. 37.8%; OR, 6.0; P < 0.001). A total of 66.1% of patients in the immunoguided arm showed a better DOOR, indicating a greater likelihood of a better outcome.
Conclusions
Prophylaxis can be prematurely discontinued in CMV-seropositive KT patients receiving ATG when CMV-CMI is recovered since no significant increase in the incidence of CMV replication or disease is observed.
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