Medical Oncology submission:
Attitudes of physicians towards assessing risk and using granulocyte-colony stimulating factor as primary prophylaxis in patients receiving chemotherapy associated with an intermediate risk of febrile neutropenia –Freyer, G et al. 2015
Supplementary Table 1Permitted chemotherapy regimens
Regimen / Drugs and dosageBreast cancer
TC (cyclophosphamide–docetaxel)[1] / Docetaxel 75 mg/m2 on day 1
Cyclophosphamide 600 mg/m2 on day 1
Repeat every 21 days for four cycles
TCH (carboplatin–docetaxel–trastuzumab)[2] / Docetaxel 75 mg/m2 on day 1
Carboplatin AUC 5–7 on day 1
Repeat every 21 days for six cycles with
trastuzumab4 mg/kg in week 1, followed by
trastuzumab2 mg/kg weekly for 17 weeks, followed bytrastuzumab6 mg/kg every 3weeks to complete 1 year of therapy
EPac (epirubicin–paclitaxel)[3] / Epirubicin 60 mg/m2 on day 1
Paclitaxel 175 mg/m2 on day 1
Repeat every 21 days
Docetaxel 100 mg/m2[4] / Docetaxel 100 mg/m2 on day 1
Repeat every 21 days for four cycles
FE100C (fluorouracil–epirubicin–cyclophosphamide)[5] / Fluorouracil 500 mg/m2
Epirubicin 100 mg/m2
Cyclophosphamide 500 mg/m2 on day 1
Repeat every 21 days for six cycles
FE90C (fluorouracil–epirubicin–cyclophosphamide)[6] / Fluorouracil 600 mg/m2
Epirubicin 90 mg/m2
Cyclophosphamide 600 mg/m2 on day 1
Repeat every 21 days for six cycles
DocPLD (docetaxel–pegylated liposomal doxorubicin)[7] / Docetaxel 60 mg/m2 on day 1
Pegylated liposomal doxorubicin 30 mg/m2
Repeat every 3 weeks for up to eight cycles
Non-small-cell lung cancer
Cisplatin–paclitaxel[8] / Paclitaxel 135 mg/m2 over 24 hours on day 1
Cisplatin 75 mg/m2 on day 2
Repeat every 21 days
Cisplatin–docetaxel[8] / Cisplatin 75 mg/m2 on day 1
Docetaxel 75 mg/m2 on day 1
Repeat every 21 days for up to six cycles
Cisplatin–etoposide[9-11] / Cisplatin 100 mg/m2 on day 1 or cisplatin 35mg/m2 on days 1–3
Etoposide 100 mg/m2 or 200 mg/m2 on days1–3
Repeat every 28 days (for cisplatin 35mg/m2, repeat every 21 days)
Cisplatin–vinorelbine[12-17] / Cisplatin 80–100 mg/m2 on day 1
Vinorelbine 25–30 mg/m2 on days 1, 8, (15) and (21)
Repeat every28 (21) days for four to six cycles
Carboplatin–paclitaxel ± bevacizumab[18] / Carboplatin AUC 5–7 on day 1
Paclitaxel 200 mg/m2 on day 1
Bevacizumab 15 mg/kg IV on day 1
Repeat every 21 days
Carboplatin–vinorelbine[19-21] / Carboplatin 300 mg/m2 (AUC 5) on day 1
Vinorelbine 30 mg/m2 (or 25 mg/m2) on days 1, 8 and (15)
Repeat every 21 or 28 days for six cycles
Carboplatin–docetaxel[13] / Docetaxel 75 mg/m2 on day 1
Carboplatin AUC 5–7 on day 1
Repeat every 21 days
Docetaxel monotherapy[22, 23] / Docetaxel 75 mg/m2 on day 1
Repeat every 21 days
Small-cell lung cancer
CAV (cyclophosphamide–doxorubicin–vincristine)[24-26] / Cyclophosphamide 800 mg/m2 on day 1 (other references: 750–1000 mg/m2)
Doxorubicin 50 mg/m2 on day 1
Vincristine 1.4 mg/m2 (maximum 2 mg/m2) on day 1 (other references: 1–2 mg/m2)
Repeat every 21 (28) days
Etoposide–carboplatin[27-29] / Etoposide 80–100 mg/m2 on days 1–3
Carboplatin AUC 5 on day 1
Repeat every 21–28 days for six cycles
Carboplatin–docetaxel[13] / Carboplatin AUC 5–7 on day 1
Docetaxel 75 mg/m2 on day 1
Repeat every 21 days
Carboplatin–vinorelbine[14, 30] / Carboplatin 300 (AUC 5)
Vinorelbine 25 (30) mg/m2 on days 1 and 8
Repeat every 4 weeks for six cycles
Cisplatin–etoposide[31, 32] / Cisplatin 100 (80) mg/m2 on days 1–3
Etoposide 100 (80) mg/m2 on days 1–3
Repeat every 21 or 28 days for six cycles
Docetaxel monotherapy[33] / Docetaxel 75 mg/m2 on day 1
Repeat every 21 days
Non-Hodgkin lymphoma
CHOP-21 (cyclophosphamide–doxorubicin–vincristine–prednisolone)[34-39] / Cyclophosphamide 750 mg/m2 on day 1
Doxorubicin 50 mg/m2 on day 1
Vincristine 1.4 mg/m2 (maximum 2 mg/m2) on day 1
Prednisolone 40–100 mg/m2 on days 1–5
Repeat every 21 days
R-CHOP-21 (cyclophosphamide–doxorubicin–vincristine–prednisolone–rituximab)[35, 40] / Rituximab 375 mg/m2 IV on day 1
Cyclophosphamide 750 mg/m2 on day 2
Doxorubicin 50 mg/m2 on day 2
Vincristine 1.4 mg/m2 (maximum 2 mg/m2) on day 2
Prednisolone 40–100 mg/m2 on days 2–6
Repeat every 21 days
AUCarea under the curve,IVintravenous
Supplementary Table 2Categorization of risk factors considered to be important when assessing FN risk
Factor / Single-level / Super-category / Sub-categoryTumor type
NHL / X / X
Lung / X
Breast / X
Other / X
Tumor stage
Metastatic versus nonmetastatic / X / X
Advancedstage versus
early stage / X
Chemotherapeutic agents in the backbone
Anthracyclinesa / X / X
Platinum-basedb / X
Taxanesc / X
Alkylating agentsd / X
Topoisomerase II inhibitorse / X
Gemcitabine / X
Topoisomerase I inhibitorsf / X
Vinorelbine / X
Other (please specify by
INN name) / X
Personal experience of FN risk of the chemotherapy regimen / X
Guidelines / X
EORTC, NCCN or ASCO / X
National/local / X
Medications taken / X
Immunosuppressives / X
Anti-infective prophylaxis / X
Other disease-/treatment-related / X
Previous chemotherapy / X
Previous radiotherapy involving
bone marrow / X
History of previous FN / X
Concurrent radiotherapy / X
Planned RDI (≥85% versus <85%) / X
Age (≥65 years versus <65 years) / X
ECOG/Karnofsky performance status / X
Baseline laboratory values/blood counts before start of chemotherapy / X
Elevated AST / X
Low WBC count or ANC / X
Anemia, low Hb / X
Lymphopenia / X
Elevated ALP / X
Low GFR / X
Elevated serum bilirubin / X
Low serum albumin / X
Nutritional statusg / X
Documented bone marrow involvement / X
Comorbidities / X
Liver disease / X
Cardiovascular disease / X
Renal disease/impaired
renal clearance / X
Female sex / X
Current infection / X
Open wounds / X
Treatment intent (curative/prolong life versus palliative) / X
Other patient-related / X
aFor e.g. doxorubicin and epirubicin;be.g.cisplatin and carboplatin;ce.g. paclitaxel and docetaxel;de.g. cyclophosphamide andifosfamide;ee.g. etoposide and mitoxantrone;fe.g. irinotecan and topotecan;ge.g. weight loss, low BMI
ALP alkaline phosphatase,ANC absolute neutrophil count,ASCO American Society of Clinical Oncology,AST aspartate aminotransferase,BMI body mass index,ECOGEastern Cooperative Oncology Group,EORTC European Organisation for Research and Treatment of Cancer,FN febrile neutropenia,GFR glomerular filtration rate,Hb hemoglobin,INN international non-proprietary name,NCCN National Comprehensive Cancer Network,NHLnonHodgkin lymphoma,RDI relative dose intensity,WBC white blood cell
Supplementary Table 3Categorization of risk factors considered important when decidingwhether to use G-CSF PP
Factor / Single-level / Super-category / Sub-categoryAge / X
Medications taken / X
Immunosuppressives / X
Antiinfective prophylaxis / X
ECOG/Karnofsky performance status / X
Baseline laboratory values/blood counts before start of chemotherapy / X
Patient lives far from the clinic/
healthcare resources / X
Retired versus employed/
active status of the patient / X
Private health insurance
of the patient / X
Outcome of the overall FN
risk assessment / X
FN risk ofchemotherapy only / X
Estimated overall FN
risk score including patientrelated risk factors / X
Treatment intent / X
Curative/prolong life / X
Palliative / X
Planned RDI (≥85% vs <85%) / X
Guidelines / X
EORTC, NCCN or ASCO / X
National/local / X
Safety risk of intensive chemotherapya / X
Safety risk of G-CSFs in generalb / X
Length of chemotherapy cyclec / X
Outpatient care of the patient / X
Hospitalized patient / X
Estimated compliance of the patient or caregiver with the treatment plan / X
Family/caregiver/nurse support to the patient / X
Local access to reimbursed
G-CSF PP / X
Regulations at hospital level / X
Regulations at regional level / X
Regulations at national level / X
Wait-and-see approach / X
Other / X
aRisk of secondary malignancies such as AML/MDS;be.g.the listed undesirable effects of the G-CSF in the respective SmPCs;cweekly, every 2 weeks, every 3 or 4 weeks etc
AML acute myeloid leukemia,ASCO American Society of Clinical Oncology,ECOG Eastern Cooperative Oncology Group,EORTC European Organisation for Research and Treatment of Cancer,FN febrile neutropenia,G-CSF granulocyte-colony stimulating factor,MDS myelodysplastic syndrome,NCCN National Comprehensive Cancer Network, PPprimary prophylaxis,RDI relative dose intensity,SmPC summary of product characteristics
Supplementary Table 4Overlap between FN risk factors in the baseline investigator and patientassessments(N=944)
Risk factor / Overlap / Investigator only / Patient onlyChemotherapy agents in the backbone / 725 (76.8) / 111 (11.8) / 63 (6.7)
Guidelines / 455 (48.2) / 218 (23.1) / 89 (9.4)
Tumor type / 452 (47.9) / 175 (18.5) / 150 (15.9)
Tumor stage / 355 (37.6) / 252 (26.7) / 78 (8.3)
Age / 327 (34.6) / 345 (36.5) / 53 (5.6)
ECOG/Karnofsky performance status / 256 (27.1) / 380 (40.3) / 64 (6.8)
Treatment intent / 202 (21.4) / 297 (31.5) / 116 (12.3)
Baseline laboratory values / 148 (15.7) / 568 (60.2) / 19 (2.0)
Comorbidities / 135 (14.3) / 497 (52.6) / 31 (3.3)
Female sex / 128 (13.6) / 144 (15.3) / 94 (10.0)
Personal experience of FN risk of the chemotherapy regimen / 123 (13.0) / 258 (27.3) / 84 (8.9)
Previous chemotherapy / 123 (13.0) / 573 (60.7) / 31 (3.3)
Nutritional status / 78 (8.3) / 416 (44.1) / 23 (2.4)
Planned RDI / 64 (6.8) / 203 (21.5) / 51 (5.4)
History of FN / 47 (5.0) / 711 (75.3) / 6 (0.6)
Documented bone marrow involvement / 41 (4.3) / 575 (60.9) / 8 (0.8)
Medications taken / 35 (3.7) / 449 (47.6) / 20 (2.1)
Previous radiotherapy involving bone marrow / 34 (3.6) / 602 (63.8) / 8 (0.8)
Current infection / 32 (3.4) / 418 (44.3) / 10 (1.1)
Open wounds / 23 (2.4) / 373 (39.5) / 8 (0.8)
Concurrent radiotherapy / 19 (2.0) / 403 (42.7) / 11 (1.2)
Other patient-related / 5 (0.5) / 19 (2.0) / 23 (2.4)
Other disease-/treatment-related / 4 (0.4) / 56 (5.9) / 7 (0.7)
Data are presented as number (%), unless otherwise stated
ECOG Eastern Cooperative Oncology Group,FN febrile neutropenia,RDIrelative dose intensity
Supplementary Table 5Overlap between GCSF PP decision factors in the baseline investigator and patientassessments (N=944)
Risk factor / Overlap / Investigator only / Patient onlyOutcome of the overall FN risk assessment / 583 (61.8) / 238 (25.2) / 62 (6.6)
Guidelines / 477 (50.5) / 187 (19.8) / 68 (7.2)
Treatment intent / 472 (50.0) / 180 (19.1) / 98 (10.4)
Age / 413 (43.8) / 311 (32.9) / 38 (4.0)
ECOG/Karnofsky performance status / 272 (28.8) / 319 (33.8) / 97 (10.3)
Baseline laboratory values / 191 (20.2) / 505 (53.5) / 14 (1.5)
Length of chemotherapy cycle / 166 (17.6) / 306 (32.4) / 24 (2.5)
Planned RDI / 100 (10.6) / 195 (20.7) / 37 (3.9)
Local access to reimbursed GCSF PP / 91 (9.6) / 160 (16.9) / 13 (1.4)
Patient lives far from the clinic/
healthcare resource / 65 (6.9) / 290 (30.7) / 36 (3.8)
Medications taken / 63 (6.7) / 461 (48.8) / 20 (2.1)
Outpatient care of the patient / 45 (4.8) / 138 (14.6) / 92 (9.7)
Estimated compliance of the patient or caregiver with the treatment plan / 41 (4.3) / 189 (20.0) / 28 (3.0)
Safety risk of GCSFs in general / 24 (2.5) / 162 (17.2) / 25 (2.6)
Family/caregiver/nurse support to the patient / 18 (1.9) / 108 (11.4) / 21 (2.2)
Safety risk of intensive chemotherapy / 15 (1.6) / 274 (29.0) / 11 (1.2)
Hospitalized patient / 12 (1.3) / 145 (15.4) / 24 (2.5)
Wait-and-see approach / 12 (1.3) / 82 (8.7) / 18 (1.9)
Retired versus employed/active status of the patient / 4 (0.4) / 100 (10.6) / 32 (3.4)
Private health insurance of the patient / 2 (0.2) / 60 (6.4) / 12 (1.3)
Other / 0 (0.0) / 5 (0.5) / 6 (0.6)
Data shown are patient number (%), unless otherwise stated
ECOG Eastern Cooperative Oncology Group,FN febrile neutropenia, G-CSF granulocyte-colony stimulating factor,PP primary prophylaxis,RDIrelative dose intensity
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