Febrile neutropenia (FN) occurrence outside of clinical trials: occurrence and predictive factors in adult patients treated with chemotherapy and an expected moderate FN risk. Rationale and design of a real-world prospective, observational, multinational study

Bernardo Leon Rapoport,Teresa Smit,Andriy Krendyukov,Ronwyn Van Eeden,Jean Klastersky,Marianne Paesmans,Matti Aapro

doi:10.1186/s12885-018-4838-z

Abstract

BackgroundFebrile neutropenia (FN) is a common occurrence during chemotherapy. Granulocyte colony-stimulating factors (G-CSFs) can significantly reduce the risk of FN. International guidelines recommend G-CSF for patients receiving chemotherapy with FN risk of ≥20% or 10% to 20% with defined risk factors. Prophylaxis is not typically recommended for FN risk of < 10%; however, few studies have investigated FN incidence in lower-risk patients in real-world settings and tried to identify higher-risk subgroups.MethodsThis real-world prospective, observational, multinational study aims to estimate the rate of development of FN with a chemotherapy line expected to be associated with a 10% to 20% risk of FN. Eligible patients (> 18 years of age) will have a solid tumour or Hodgkin/non-Hodgkin lymphoma and a planned chemotherapy regimen with expected risk of FN of 10% to 20% (according to published guidelines). Patients will be observed for the duration of the chemotherapy line (first cycle administered without FN prophylaxis). Primary endpoint is incidence of FN after the first chemotherapy cycle. Secondary outcomes include: FN-associated morbidity and mortality; time to first FN occurrence; other FN risk factors and impact of FN on quality of life. A risk model using occurrence of FN as a binary outcome will be developed. Data will be stratified by age, comorbidities and other risk factors.DiscussionThis study will provide insight into the real FN risk for common chemotherapy regimens and predictive factors for FN, including patients generally excluded from randomised clinical trials, from which reported FN rates have been variable. This study builds on knowledge of predictive factors from other research and will provide information on patients with 10% to 20% FN risk.

Highlights

Febrile neutropenia (FN) is a common occurrence during chemotherapy
In a study of Granulocyte colony-stimulating factors (G-CSFs) in patients with early breast cancer treated with epirubicin-cyclophosphamide chemotherapy, the rate of FN was 1% in the G-CSF arms compared with 7% in the control arms (P = .004) [7]
This real-world study will include patients who are generally excluded from randomised controlled trials (RCTs) and analyses will be performed on data stratified by age to provide a greater understanding of FN risk in elderly patients receiving myelosuppressive chemotherapy regimens with an expected moderate (10% to 20%) FN risk

Summary

Methods

Aim The primary objective of this real-world study is to estimate the rate of patients who will develop at least one episode of FN when treated with a chemotherapy regimen (new chemotherapy line) expected to be associated with a moderate (10% to 20%) risk of FN, according to published guidelines. Quality of life assessment Assuming a mean overall Trial Outcome Index-Neutropenia Score of − 0.61 for patients with grade 3 to 4 neutropenia and an estimated 20% of patients expected to develop grade 3 to 4 neutropenia by day 8 of the first chemotherapy cycle, ~ 30 patients with grade 3 to 4 neutropenia should be recruited to detect this effect size (two-sided α = 5%, β = 10%); meaning ~ 150 patients with a QoL assessment should be recruited in total Based on this calculation, 2 to 3 sites are required to participate in the QoL sub-study. Interval between cycles: 3 weeks Cyclophosphamide: 1000 mg/m2 Doxorubicin: 45 mg/m2 Etoposide: 300 mg/m2

Discussion

Background

Findings