Febrile neutropenia in chemotherapy treated small-cell lung cancer patients
Background: Chemotherapy with platinum agent and etoposide for small cell lung cancer (SCLC) is supposed to be associated with intermediate risk (10-20%) of febrile neutropenia (FN). Primary prophylaxis with granulocyte colony-stimulating factors (G-CSFs) is not routinely recommended by the treatment guidelines. However, in clinical practice FN is often observed with standard etoposide/platinum regimen. The aim of this analysis was to evaluate the frequency of severe (grade 3/4) neutropenia and febrile neutropenia (FN) and to explore the association between severe neutropenia and etoposide peak plasma levels in the first cycle of etoposide/platinum chemotherapy for advanced small cell lung cancer (SCLC).
Methods: The case series based analysis of 17 patients with advanced SCLC treated with platinum/etoposide chemotherapy without concurrent irradiation in the frame of a prospective etoposide pharmacokinetics study was performed. Grade 3/4 neutropenia and FN, observed after the first cycle are reported. The neutrophil counts were determined on day one of the second cycle unless symptoms potentially related to neutropenia occurred. Adverse events were classified according to Common Toxicity Criteria 4.0. Etoposide plasma concentrations were measured in the scope of pharmacokinetic study.
Results: Two out of 17 patients received primary GCS-F prophylaxis. In 15 patient without primary prophylaxis the rates of both grade 3/4 neutropenia and FN were high (8/15 (53.3%) and 2/15 (13.3%), respectively), already in the first cycle of chemotherapy. One patient died due to febrile neutropenia related pneumonia. Neutropenic events are assumed to be related to increased etoposide plasma concentrations after a standard etoposide and cisplatin dose. While the mean etoposide peak plasma concentration in the first cycle of chemotherapy was 17.6 mg/l, the highest levels of 27.07 and 27.49 mg/l were determined in two patients with FN.
Conclusions: Our study indicates that there is a need to reduce the risk of neutropenic events in chemotherapy treated advanced SCLC, starting in the first cycle. Mandatory use of primary G-CSF prophylaxis might be considered. Alternatively, use of improved risk models for identification of patients with increased risk for neutropenia and individualization of primary prophylaxis based on not only clinical characteristics but also on etoposide plasma concentration measurement, could be a new, promising options that deserves further evaluation.