Purpose: Neutropenia is one of the most frequent causes for dose limiting toxicities of cancer chemotherapy. Febrile neutropenia (FN) is a common complication of neutropenia and is usually treated with immediate hospitalization, intra-venous anti-infective drugs and may result in chemotherapy dose reductions and mortality. Prophylactic use of granulocyte colony stimulating factors (rG-CSF; filgrastim) administered daily, is proven in randomized controlled trials (RCT) as capable of reducing the risk and severity of FN, and length of hospitalization (LOS). Recent RCTs demonstrate that Pegfilgrastim, a new, long-acting pegylated form of filgrastim administered once per cycle is at least as safe and as effective as filgrastim. While current clinical guidelines recommending the use of G-CSF with chemotherapy regimens associated with FN risk>40% are undergoing revision, our analysis is designed to determine whether the additional cost of pegfilgrastim is offset by the cost savings associated with a lower incidence of FN, and establish an economic threshold for its use.

Methods: A cost-minimization decision model was developed, incorporating hospitalization, outpatient treatment and medical staff costs. Probabilities are based on published RCTs of pegfilgrastim. Direct medical cost estimates (US $2004) were based on discharge summaries from 115 US academic hospitals (University HealthSystem Consortium) and claims data from MarketScan (maintained by Medstat). Drug costs were based on published average wholesale price. FN risk threshold was calculated, and univariate, multivariate and Monte-Carlo simulation were performed to assess model robustness.

Results: Mean cost/day was $1900 for surviving patients, and $3000 for dying patients. Under baseline conditions (risk of FN=20%, relative risk reduction (RRR) with pegfilgrastim= 0.9) total net savings with pegfilgrastim are $-802 per chemotherapy cycle and cost neutral threshold for FN risk is 15.2%. Sensitivity analyses demonstrate robustness of the model for values of RRR> 0.61, cost/day for surviving patients> $1340, and cost of pegfilgrastim<$3300. Distribution of incremental costs (savings) estimated from Monte Carlo simulation indicated mean savings of $-809 (STD=$1181) per cycle, with pegfilgrastim being the preferred strategy in 74% of iterations.

Conclusions: Incorporating data from different sources into a clinical decision model demonstrates that prophylactic pegfilgrastim is cost-saving at levels of FN< 20%, which are substantially lower than current guideline recommendations. In addition to compelling evidence for clinical benefit, primary prophylaxis with pegfilgrastim should be considered on the basis of cost.