Relationship between severity and duration of chemotherapy-induced neutropenia and risk of infection among patients with nonmyeloid malignancies.

PURPOSE: Chemotherapy-induced neutropenia (CIN) may increase infection risk for cancer patients; however, there is limited understanding on the quantitative relationships between severity and duration of CIN and infection risk. METHODS: This study combined individual data from adult cancer patients receiving no granulocyte colony-stimulating factor during the first chemotherapy cycle in six trials. We used area over the curve (AOC) of absolute neutrophil count (ANC) time-response curve (below different thresholds) to measure the combined effect of severity and duration of CIN. Time-dependent Cox proportional hazards models quantified the hazard of first infection associated with duration of grade 4 or grade 3/4 CIN and the hazard associated with AOC. RESULTS: We analyzed data from 271 patients who had small cell lung cancer, non-Hodgkin's lymphoma, head and neck cancer, or breast cancer; 63.8 % of the patients had advanced cancer, and 77.5 % received chemotherapy regimens with high risk of febrile neutropenia. In the first cycle, 18.8 % of the patients had infection-related hospitalizations. Each additional day patients had grade 3/4 or grade 4 CIN was associated with 28 % (95 % CI 7, 51 %) and 30 % (95 % CI 10, 54 %) increased risk of infection-related hospitalization, respectively. Each unit increase in AOC (day × 10(9)/L ANC), with threshold of ANC < 0.5 × 10(9)/L, was associated with a significantly increased risk of infection-related hospitalization (hazard ratio 1.98; 95 % CI 1.35, 2.90). CONCLUSIONS: Infection risk increases dramatically with each additional day of grade 3 or 4 CIN. Interventions limiting CIN severity and duration are of critical importance to reduce infection risk in cancer patients receiving chemotherapy.

Trajectory of absolute neutrophil counts in patients treated with pegfilgrastim on the day of chemotherapy versus the day after chemotherapy.

PURPOSE: Risk of infection increases with severity and duration of chemotherapy-induced neutropenia (CIN). Pegfilgrastim is approved for use on the day after chemotherapy to reduce incidence of infection, as manifested by febrile neutropenia (FN), in patients receiving myelosuppressive chemotherapy. In this study, we compared severity and duration of absolute neutrophil count (ANC) suppression in patients who received pegfilgrastim on the same day as chemotherapy versus the next day. METHODS: We combined individual patient data from four Amgen-sponsored clinical trials in which patients with cancer were randomized to receive pegfilgrastim either the same day as chemotherapy or the next day. Severity and duration of ANC suppression were calculated using area over the curve (AOC, the area over the ANC-time response curve and below a given clinical threshold). AOC of ANC and incidences of CIN and FN were compared by day of pegfilgrastim use. RESULTS: The analysis included 95 same-day patients and 97 next-day patients. Despite similar ANC at baseline, ANC at nadir was higher among next-day patients than same-day patients. Mean AOC of ANC (cutoff 0.5 × 10(9)/L) among next-day patients was lower by 0.30 (95 % confidence interval: 0.16, 0.43) 10(9)/L × day than same-day patients in cycle 1. Next-day patients had lower incidences of CIN than same-day patients, but there were no significant differences in incidences of FN. CONCLUSIONS: Patients who received pegfilgrastim the day after chemotherapy had less severe and shorter suppression of ANC than patients who received pegfilgrastim the same day as chemotherapy.