Febrile neutropenia and reduced dose intensity in patients with aggressive non-Hodgkin's lymphoma (NHL) treated with CHOP and CNOP

Abstract

6599 Background: Myelosuppression remains the major dose-limiting toxicity of systemic chemotherapy in patients with intermediate grade NHL. Recent studies support the importance of sustaining dose intensity in this setting. Methods: A survey of 1243 community oncology practices including nearly 5500 patients receiving chemotherapy for NHL was undertaken to evaluate the impact of demographic, clinical and treatment related factors on delivered dose intensity. Relative dose intensity (RDI) was estimated for each drug as the ratio of dose intensity received to standard dose intensity for each regimen. Results: This analysis is limited to 3536 patients with aggressive NHL (Working Formulation D-H) treated with CHOP (87%) or CNOP (13%) chemotherapy over a 10-year period from 1992 to 2001. Average age was 61 years with 45% ≥65 years and 54% male. Diffuse large cell histology was reported in 57%. Febrile neutropenia (FN) occurred one or more times in 21% of patients of which 76% required hospitalization. In multivariate analysis, significant risk factors for FN included age >65 (OR=1.8), female gender (OR=1.5), heart disease (OR=3.3), liver disease (OR=3.4) and ECOG performance status ≥2 (OR=2.1). Average RDI to reference standard was 84% with averaged planned and unplanned reductions in RDI of 4.5% and 11.5% respectively. Forty-five percent of patients received average RDI <85%. Risk factors for average RDI <85% included age ≥ 65 (53%), stage 4 (53%), ECOG performance status ≥ 2 (57%), female gender (48%), body mass index (BMI) ≥ 30 (50%) and hospitalization for FN (54%). Colony-stimulating factors were used in 41% of patients primarily in response to a previous episode of FN. In multivariate analysis, significant independent risk factors for average RDI <85% included age >65 (OR=1.8), female gender (OR=1.2), stage 4 (OR=1.6), CHOP (OR=1.3), BMI ≥30 (1.4) and previous FN hospitalization (1.4). Conclusions: Nearly one-half of patients with aggressive NHL histology treated with CHOP-like regimens experienced substantial dose reductions related to age, stage, gender, obesity, regimen and previous FN hospitalization. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen, Inc. Amgen, Inc. Amgen; Anormed