Rates of febrile neutropenia and its causes in the real world

Figures & data

Table 1. Characteristics of patient hospitalized for febrile neutropenia (patients baseline characteristics are reported per patients, while other characteristic such as ECOG or treatment intent, are reported per episode of febrile neutropenia, as they may evolve for patient presenting with multiple episodes of febrile neutropenia).

Median age (range)		58 (20–84) years
Sex	Female	43/99 (43%)
	Male	57/99 (57%)
Cancer type	Lymphomas	21/99 (21%)
	Lung	17/99 (17%)
	Breast	15/99 (15%)
	Upper GI	14/99 (14%)
	Head & neck	5/99 (5%)
	Lower GI	4/99 (4%)
	Gyn	4/99 (4%)
	Testis	4/99 (4%)
	CNS	4/99 (4%)
ECOG	0	52/109 (48%)
	1	33/109 (30%)
	2	15/109 (14%)
	3–4	9/109 (8%)
Treatment intent	Curative	48/109 (44%)
	Adjuvant	9/109 (8%)
	Neoadjuvant	11/109 (10%)
	Palliative	41/109 (38%)
Cycle with febrile neutropenia	1	60/109 (55%)
	2–3	26/109 (24%)
	≥4	23/109 (21%)
Comorbidities	Cardiovascular disease	18/99 (18%)
	Lung disease	9/99 (9%)
	Chronic kidney disease	6/99 (6%)
	Chronic liver disease	4/99 (4%)
	Other significant	6/99 (6%)
Other concomitant grade 3 to 5 chemotherapy related adverse events	Platelet count decreased	50/109 (46%)
	Anemia	37/109 (34%)
	Diarrhea	5/109 (5%)
	Acute kidney injury	4/109 (4%)
	Mucositis oral	3/109 (3%)
	Vomiting	2/109 (2%)
	Other (rash maculopapular, jejunal hemorrhage)	2/109 (2%)

ECOG: Eastern Cooperative Oncology Group; GI: Gastrointestinal.

Table 2. Most common regimens associated with febrile neutropenia at our institution.

Regimens	FN hospitalizations	Total patients	FN hospitalizations frequency (% of patient)	FN frequency in clinical trials	Regimen FN risk category
EC	8	116	6.89	<1%^23-5.4%^24	Low
Carboplatin etoposide	7	59	11.86	4.5%^25-13.2%^26	Intermediate
Cisplatin etoposide	5	14	35.71	4%^27- 9.9%^28 -12%^29	Intermediate
RTX – cisplatin	5	53	9.43	2%^30-6%^31	Low
FLOT	5	40	12.50	2%^32	Low
(R-)CHOP	7	59	11.86	17%^33	Intermediate
Carboplatin AUC5 paclitaxel q3W	4	60	6.7	<3%^34-9%^35	Low
Carboplatin AUC2 paclitaxel qW	2	86	2.32	3%^36	Low
R-DA-EPOCH^†	6	12	50	35%^33	High
FOLFIRI	3	27	11.11	7%^37	Low
BEP^†	3	40	7.50	15%^38–19.4%^39	Intermediate

Comparison of febrile neutropenia rate observed in the cohort with the literature.

† G-CSF is systematically prescribed as part of these protocols.

AUC: Area under the curve; BEP: Bleomycin 30 mg D1 D8 D15, etoposide 100 mg/m2 D1-D5, cisplatin 20 mg/m2 D1-D5, pegfilgrastim 6 mg D6, q3W; Carboplatin etoposide: Carboplatin AUC 5 D1, etoposide 100 mg/m2 D1-D3 q3w; Ciplatin etoposide: Cisplatin 100 mg/m2 D1, etoposide 100 mg/m2 D1-D3 q3w; EC: Cyclophosphamide 600 mg/m² D1, Epirubicin 90 mg/m² D1 q3w; FOLFIRI: 5-FU 400 mg/m2 D1, 5-FU 2400 mg/m2 over 44 h, leucovorin 30 mg D1, irinotecan 180 mg/m2 D1 q2w; FLOT: 5-FU 2000 mg/m² over 24 h, leucovorin 30 mg D1, Docetaxel 50 mg/m² D1, oxaliplatin 85 mg/m² D1 q2w; FN: Febrile neutropenia; R-CHOP: Rituximab 375 mg/m² D1, cyclophosphamide 750 mg/m² D1, doxorubicin 50 mg/m² D1, vincristine 1.4 mg/m² D1, prednisone 40 mg/m² D1-D5; R-DA-EPOCH: Rituximab 375 mg/m² D1, dose-adjusted etoposide 50–124 mg/m² (depending on dose level) D1-D5, prednisone 120 mg/m² D1-D5, vincristin 0.4 mg/m² D1-D4, cyclophosphamide 750–1866 mg/m² (depending on dose level) D5, doxorubicin 10–25 mg/m² (depending on dose level) D1-D4, filgrastim 0.5 mioU/kg starting from D6 until absolute neutrophile count >5000 cells/ul; q3w; RTX-cisplatin: Cisplatin 100 mg/m2 D1 q3w with concurrent radiotherapy.

Figure 1. Comparison of febrile neutropenia rates in the cohort with data from clinical trials.

AUC: Area under the curve; BEP: Bleomycin 30 mg D1 D8 D15, etoposide 100 mg/m2 D1-D5, cisplatin 20 mg/m2 D1-D5, pegfilgrastim 6 mg D6, q3W; Carboplatin etoposide: Carboplatin AUC 5 D1, etoposide 100 mg/m² D1-D3 q3w; Ciplatin etoposide: Cisplatin 100 mg/m² D1, etoposide 100 mg/m2 D1-D3 q3w; EC: Cyclophosphamide 600 mg/m² D1, Epirubicin 90 mg/m² D1 q3w; FLOT: 5-FU 2000 mg/m² over 24 h, leucovorin 30 mg D1, Docetaxel 50 mg/m² D1, oxaliplatin 85 mg/m² D1 q2w; R-CHOP: Rituximab 375 mg/m² D1, cyclophosphamide 750 mg/m² D1, doxorubicin 50 mg/m² D1, vincristine 1.4 mg/m² D1, prednisone 40 mg/m² D1-D5; R-DA-EPOCH: Rituximab 375 mg/m² D1, dose-adjusted etoposide 50–124 mg/m² (depending on dose level) D1-D5, prednisone 120 mg/m² D1-D5, vincristin 0.4 mg/m² D1-D4, cyclophosphamide 750–1866 mg/m² (depending on dose level) D5, doxorubicin 10–25 mg/m² (depending on dose level) D1-D4, filgrastim 0.5 mioU/kg starting from D6 until absolute neutrophile count >5000 cells/ul, q3w; RTX-cisplatin: Cisplatin 100 mg/m2 D1 q3w with concurrent radiotherapy.

Table 3. Among patients hospitalized for febrile neutropenia, potential drug interaction between chemotherapy and comedications: associations that are usually contra-indicated.

Chemotherapy regimen	Co-medications with major potential interaction	Number of cases
Methotrexate IV	Esomeprazole	2/109
Dacarbazine	Omeprazole	1/109
Docetaxel	Fluoxetine	1/109
Etoposide	Carvedilol	1/109
Cyclophosphamide	Allopurinol	1/109
Docetaxel	Darunavir/ritonavir	1/109
Methotrexate IV	Torasemide	1/109
Methotrexate IV	Trimethoprim-sulfamethoxazole	1/109
Methotrexate IV	Ibuprofen	1/109
Etoposide	Amiodarone	1/109
Methotrexate IV	Etoricoxib	1/109

Comedications: treatment taken at the time of chemotherapy administration.

Table 4. Patients hospitalized for febrile neutropenia who presented significant abnormal pre-treatment laboratory values, and the regimen they received, with dose-adjustment.

Patients	Laboratory abnormality	Chemotherapy regimen	Treatment intent	Dose reduction
Male, 52 y.o.	Kidney failure	5-FU irinotecan	Palliative	no (100%)
Female 47 y.o.	Neutrophil count decreased	Carboplatin gemcitabine	Palliative	80%
Female 67 y.o.	Abnormal liver test	Eribulin	Palliative	no (100%)
Male 69 y.o.	Neutrophil count decreased; kidney failure; platelets count decreased	Cyclophosphamide	Palliative	50%
Male 69 y.o.	Kidney failure	Cisplatin ifosfamide paclitaxel (TIP)	Curative	no (100%)
Female 60 y.o.	Severe anemia	Carboplatin irinotecan	Curative	no (100%)
Male 59 y.o.	Severe anemia	Capecitabine oxaliplatin	Palliative	no (100%)
Female 54 y.o.	Abnormal liver test	Carboplatin cyclophosphamide	Palliative	50%
Female 58 y.o.	Platelets count decreased	Carboplatin paclitaxel	Palliative	no (100%)
Male 59 y.o.	Platelets count decreased	Capecitabine temozolomide	Palliative	85%

y.o.: Years old.

Data availability statement

The datasets generated and analyzed during the current study are available from the corresponding author on reasonable request.