Febrile neutropenia in chemotherapy treated small-cell lung cancer patients

Abstract

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. Primary prophylaxis with granulocyte colony-stimulating factors (G-CSFs) is not routinely recommended by the treatment guidelines. However, in clinical practice febrile neutropenia is often observed with standard etoposide/platinum regimen. The aim of this analysis was to evaluate the frequency of neutropenia and febrile neutropenia in advanced SCLC patients in the first cycle of standard chemotherapy. Furthermore, we explored the association between severe neutropenia and etoposide peak plasma levels in the same patients.Methods.The case series based analysis of 17 patients with advanced SCLC treated with standard platinum/etoposide chemotherapy, already included in the pharmacokinetics study with etoposide, was performed. Grade 3/4 neutropenia and febrile neutropenia, 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. Additionally, association between severe neutropenia and etoposide peak plasma concentrations, which were measured in the scope of pharmacokinetic study, was explored.Results.Two out of 17 patients received primary GCS-F prophylaxis. In 15 patient who did not receive primary prophylaxis the rates of both grade 3/4 neutropenia and febrile neutropenia 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 febrile neutropenia.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.

Outcome of severe infections in afebrile neutropenic cancer patients

“…2,3 Fever remains the most prevalent and evident sign of infection in neutropenic cancer patients and early initiation of broad-spectrum antibiotic therapy significantly reduces mortality in these patients. 4–7 …”

Pharmacokinetic interaction between mitotane and etoposide in adrenal carcinoma: a pilot study

“…Kukec et al . showed that high plasma etoposide exposure was associated with both longer survival and increased severity of neutropenia in SCLC patients (4). Hence, the neutrophil blood count could be used as a surrogate of plasma drug exposure and therefore could be helpful to guide dosing optimization.…”

“…However, overall response rate (23%) and progression-free survival (5 months) remain disappointing. Furthermore, lower rates of severe hematological toxicities are observed with EDP-mitotane regimen than with platinum-etoposide in small-cell lung cancer (SCLC) patients (11 vs 53% of grade 3–4 neutropenia) (4). Since neutropenia is commonly associated with etoposide AUC (5), this may indicate a lower plasma etoposide exposure in ACC patients treated with mitotane.…”

Hematopoietic growth factors in lung cancer

“…Generally, the higher risk of febrile neutropenia with common regimens for SCLC compared with NSCLC makes the addition of G-CSFs appealing. Retrospective data from SCLC patients receiving standard treatment with cisplatin-etoposide suggest that, although the risk for febrile neutropenia is considered intermediate, it is still relevant and susceptible of significant benefit with primary prophylaxis [30]. Most clinical trials involving SCLC employed dose-dense or dose-intense regimens, and in general schedules characterized by high risk of febrile neutropenia, such as cyclophosphamidedoxorubicin-etoposide, cyclophosphamide-epirubicin-etoposide or vincristine-ifosfamide-carboplatinetoposide.…”