title: Predictive modeling of the outcomes of chemotherapy-induced (febrile) neutropenia prophylaxis with biosimilar filgrastim (MONITOR-GCSF study).
abstract: Risk models of chemotherapy-induced (CIN) and febrile neutropenia (FN) have to date focused on determinants measured at the start of chemotherapy. We extended this static approach with a dynamic approach of CIN/FN risk modeling at the start of each cycle.
  
  
  
  We applied predictive modeling using multivariate logistic regression to identify determinants of CIN/FN episodes and related hospitalizations and chemotherapy disturbances (CIN/FN consequences) in analyses at the patient ('ever' during the whole period of chemotherapy) and cycle-level (during a given chemotherapy cycle). Statistical dependence of cycle data being 'nested' under patients was managed using generalized estimation equations. Predictive performance of each model was evaluated using bootstrapped c concordance statistics.
  
  
  
  Static patient-level risk models of 'ever' experiencing CIN/FN adverse events and consequences during a planned chemotherapy regimen included predictors related to history, risk factors, and prophylaxis initiation and intensity. Dynamic cycle-level risk models of experiencing CIN/FN adverse events and consequences in an upcoming cycle included predictors related to history, risk factors, and prophylaxis initiation and intensity; as well as prophylaxis duration, CIN/FN in prior cycle, and treatment center characteristics.
  
  
  
  These 'real-world evidence' models provide clinicians with the ability to anticipate CIN/FN adverse events and their consequences at the start of a chemotherapy line (static models); and, innovatively, to assess risk of CIN/FN adverse events and their consequences at the start of each cycle (dynamic models). This enables individualized patient treatment and is consistent with the EORTC recommendation to re-appraise CIN/FN risk at the start of each cycle. Prophylaxis intensity (under-, correctly-, or over-prophylacted relative to current EORTC guidelines) is a major determinant. Under-prophylaxis is clinically unsafe. Over-prophylaxis of patients administered chemotherapy with intermediate or low myelotoxicity levels may be beneficial, both in patients with and without risk factors, and must be validated in future studies.
authors: Institut Multidisciplinaire d'Oncologie, Clinique de Genolier, Genolier, Switzerland maapro@genolier.net.
authors: M
authors: M
authors: Aapro
authors: Medizinische Abteilung I-Oncology and Hematology, Wilhelminenspital, Wien, Austria.
authors: H
authors: H
authors: Ludwig
authors: Department of Oncology, Universitaetsklinikum Hamburg Eppendorf, Hamburg, Germany.
authors: C
authors: C
authors: Bokemeyer
authors: Division of Medical Oncology, Department of Hematology-Oncology, Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Spain.
authors: P
authors: P
authors: Gascón
authors: Department of Oncology and Hematology, Azienda Ospedaliero Universitaria S. Giovanni Battista di Torino, Torino, Italy.
authors: M
authors: M
authors: Boccadoro
authors: Matrix45, Tucson, AZ, USA.|Department of Statistics, Universitaet Basel, Basel, Switzerland.
authors: K
authors: K
authors: Denhaerynck
authors: Hexal AG, Holzkirchen, Germany.
authors: A
authors: A
authors: Krendyukov
authors: Hexal AG, Holzkirchen, Germany.
authors: M
authors: M
authors: Gorray
authors: Matrix45, Tucson, AZ, USA.
authors: K
authors: K
authors: MacDonald
authors: Matrix45, Tucson, AZ, USA.|Center for Health Outcomes and PharmacoEconomic Research, University of Arizona, Tucson, AZ, USA.
authors: I
authors: I
authors: Abraham
mesh_terms: D000328:Adult; D000368:Aged; D059451:Biosimilar Pharmaceuticals / Q000008:administration & dosage / Q000009:adverse effects*; D064420:Drug-Related Side Effects and Adverse Reactions / Q000473:pathology*; D064147:Febrile Neutropenia / Q000139:chemically induced / Q000473:pathology*; D005260:Female; D000069585:Filgrastim / Q000008:administration & dosage* / Q000009:adverse effects; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D012307:Risk Factors
chemical_list: D059451:Biosimilar Pharmaceuticals; D016179:Granulocyte Colony-Stimulating Factor; D000069585:Filgrastim
keywords: biosimilar; chemotherapy-induced neutropenia; febrile neutropenia; filgrastim; granulocyte colony-stimulating factor; modeling