The risk of febrile neutropenia in breast cancer patients following adjuvant chemotherapy is predicted by the time-course of IL-6 and CRP by modelling

Summary

Aims

Early identification of patients with febrile neutropenia (FN) is desirable for initiation of preventive treatment, e.g. antibiotics. In this study, the time-courses of two inflammation biomarkers, IL-6 and CRP, following adjuvant chemotherapy of breast cancer, were characterised. The potential to predict development of FN by IL-6 and CRP, and other model-derived and clinical variables, was explored.

Methods

The IL-6 and CRP time-courses in cycles 1 and 4 of breast cancer treatment were described by turnover models where the probability for an elevated production following initiation of chemotherapy was estimated. Parametric time-to-event models were developed to describe FN occurrence to assess 1) predictors available before chemotherapy is initiated, 2) predictors available before FN occurs and 3) predictors available when FN occurs.

Results

The IL-6 and CRP time-courses were successfully characterised with peak IL-6 typically occurring two days prior to CRP peak. Of all evaluated variables the CRP time-course was most closely associated with the occurrence of FN. Since the CRP peak typically occurred at the time of FN diagnosis it will however have limited value for identifying the need of preventive treatment. The time-course of IL-6 was the predictor that could best forecast FN events. Of the variables available at baseline, age was the best, although in comparison, a relatively weak predictor.

Conclusions

The developed models add quantitative knowledge about IL-6 and CRP and their relationship to the development of FN. The study suggests that IL-6 may have potential as a clinical predictor of FN if monitored during myelosuppressive chemotherapy.

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