Abstract
PurposeTo investigate whether a more frequent monitoring of the absolute neutrophil counts (ANC) during myelosuppressive chemotherapy, together with model-based predictions, can improve therapy management, compared to the limited clinical monitoring typically applied today.MethodsDaily ANC in chemotherapy-treated cancer patients were simulated from a previously published population model describing docetaxel-induced myelosuppression. The simulated values were used to generate predictions of the individual ANC time-courses, given the myelosuppression model. The accuracy of the predicted ANC was evaluated under a range of conditions with reduced amount of ANC measurements.ResultsThe predictions were most accurate when more data were available for generating the predictions and when making short forecasts. The inaccuracy of ANC predictions was highest around nadir, although a high sensitivity (≥90%) was demonstrated to forecast Grade 4 neutropenia before it occurred. The time for a patient to recover to baseline could be well forecasted 6 days (±1 day) before the typical value occurred on day 17.ConclusionsDaily monitoring of the ANC, together with model-based predictions, could improve anticancer drug treatment by identifying patients at risk for severe neutropenia and predicting when the next cycle could be initiated.
Highlights
The dose-limiting toxicity for most cytotoxic chemotherapeutic drugs in use today is bone-marrow toxicity [1]
Docetaxel is a commonly used anti-cancer agent [5,6,7] that possess pronounced myelosuppressive properties [8], which exposes the patient to a high risk for severe neutropenia and life-threatening conditions such as febrile neutropenia (FN)
absolute neutrophil count (ANC) values were simulated for 600 patients from the earlier described myelosuppression model [14, 16] where the time-course of docetaxel-induced neutropenia had been characterized
Summary
The dose-limiting toxicity for most cytotoxic chemotherapeutic drugs in use today is bone-marrow toxicity [1]. Docetaxel is a commonly used anti-cancer agent [5,6,7] that possess pronounced myelosuppressive properties [8], which exposes the patient to a high risk for severe neutropenia and life-threatening conditions such as febrile neutropenia (FN). Prior to each administration of cytotoxic drugs, the absolute neutrophil count (ANC) is measured to confirm adequate levels, i.e. ANC ≥ 1.5 × 109 cells/L for docetaxel (Taxotere® label). Potential limitations of a sparse ANC monitoring include (1) delay in identification of patients at high risk of experiencing life-threatening conditions, (2) inconvenience for the patient and the clinic if the cycle needs to be delayed due to low ANC [10, 11] the same day the patient is scheduled for the cycle, and (3) too cautious choice of dose and thereby suboptimal therapy
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