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Table 1 Description of trials of primary G-CSFs (vs. no primary G-CSF, or vs. each other)

From: Granulocyte colony-stimulating factors for febrile neutropenia prophylaxis following chemotherapy: systematic review and meta-analysis

Trial Study design Cancer type Cancer stage Patient age Chemotherapy regimen N cycles (max) Cycle length Arm 1 G-CSF strategy b Arm 1: N analysed Arm 1: days primary
G-CSF
Arm 2 G-CSF strategy b Arm 2: N analysed Arm 2: days primary
G-CSF
FN definition
Pegfilgrastim
vs. no primary
G-CSF
              
a Romieu 2007[23] RCT, phase II, OL Breast cancer Stage II-III, node-positive Age ≥ 65. Median 68, range 65-77 FEC-100 6 (FN reported cycle 1 only) 3 weeks Pegfilgrastim primary: 6 mg day 2 30 1 No primary G-CSF, pegfilgrastim secondary (following FN or neutropenia) 29 0 Fever + ANC < 1 × 109/l
Vogel 2005[21] RCT, phase III, DB Breast cancer 62% stage IV, 38% other stages Mean age 52, range 21-88 Docetaxel 100 mg/m2 4 3 weeks Pegfilgrastim primary: 6 mg day 2 463 1 Placebo primary, pegfilgrastim secondary (following FN) 465 0 Fever + ANC < 0.5 × 109/l
a Hecht 2009[24] RCT, phase II Colorectal cancer NR NR FOLFOX (49%), FOLFIRI (26%) or FOIL (25%) 4 2 weeks Pegfilgrastim primary: 6 mg day 4 123 1 Placebo primary 118 0 Grade 3-4 FN (assumed fever + ANC < 1 × 109/l)
a Balducci 2007: NHL[22] RCT, OL NHL 38% stage I-II, 62% stage III-IV Age ≥ 65. Median 72, range 65-88 CHOP or R-CHOP 6 3 weeks Pegfilgrastim primary: 6 mg day 2 73 1 No primary G-CSF, pegfilgrastim secondary (at physician's discretion) 73 0 Fever + ANC < 1 × 109/l
a Balducci 2007: solid tumour[22] RCT, OL Solid tumour (lung, ovarian, breast) 31% stage I-II, 69% stage III-IV Age ≥ 65. Median 72, range 65-88 One of 15 regimens with mild-to-moderate risk of neutropenia 6 3 weeks Pegfilgrastim primary: 6 mg day 2 343 1 No primary G-CSF, pegfilgrastim secondary (at physician's discretion) 343 0 Fever + ANC < 1 × 109/l
Filgrastim vs. no primary
G-CSF
              
a del Giglio 2008[33] RCT, DB Breast cancer 21% high-risk stage II,
53% stage III,
25% stage IV
Mean age 51, range 25-75 Doxorubicin 60 mg/m2/docetaxel 75 mg/m2 4 (FN reported cycle 1 only) 3 weeks Filgrastim primary (Neupogen or XM02): 5 ug/kg/d from day 2 up to 14d or to ANC = 10 × 109/l 276 5 to 14 (median 9-10) Placebo in cycle 1; filgrastim (XM02) in subsequent cycles 72 0 (cycle 1) Fever + ANC < 0.5 × 109/l
Timmer-Bonte 2005[29] RCT, phase III, OL SCLC 69% extensive, 31% limited Age range 36-81 CDE 5 3 weeks Filgrastim primary: 300/450 ug/d from day 4; prophylactic antibiotics 90 10 No primary G-CSF; prophylactic antibiotics 85 0 Fever + ANC < 0.5 × 109/l
Trillet-Lenoir 1993[30] RCT, DB SCLC 64% extensive, 36% limited Median 59 CDE 6 3 weeks Filgrastim primary: 230 ug/m2/d from day 4 up to 14d or until ANC = 10 × 109/l 65 9 to 14 Placebo primary 64 0 Fever + ANC < 1 × 109/l
Crawford 1991[31] RCT, DB SCLC 72% extensive, 28% limited Age range 31-80 CDE 6 3 weeks Filgrastim primary: 230 ug/m2/d from day 4 up to 14d or until ANC = 10 × 109/l 95 9 to 14 Placebo primary; secondary G-CSF 104 0 Fever + ANC < 1 × 109/l
Doorduijn 2003[25] RCT, OL Aggressive NHL Stage II-IV Age ≥ 65. Median 72, range 65-90 CHOP 6 to 8 3 weeks Filgrastim primary: 300 ug/d from day 2 for 10d 197 10 No primary G-CSF 192 0 FN not defined in terms of ANC
Osby 2003 (CHOP)[26] RCT, OL Aggressive NHL Stage II-IV Age ≥ 60. Median 71, range 60-86 CHOP 4 to 8 (most 8) 3 weeks Filgrastim primary: 5 ug/kg/d from day 2 up to 14d or until ANC = 10 × 109/l 101 10 to 14 No primary G-CSF 104 0 Fever + ANC < 0.5 × 109/l
Osby 2003 (CNOP)[26] RCT, OL Aggressive NHL Stage II-IV Age ≥ 60. Median 71, range 60-86 CNOP 4 to 8 (most 8) 3 weeks Filgrastim primary: 5 ug/kg/d from day 2 up to 14d or until ANC = 10 × 109/l 125 10 to 14 No primary G-CSF 125 0 Fever + ANC < 0.5 × 109/l
Zinzani 1997[27] RCT, OL Aggressive NHL Stage II-IV Age ≥ 60. Age range 60-82 VNCOP-B 8 1 week (differs alternate weeks) Filgrastim primary: 5 ug/kg/d from day 3; prophylactic antibiotics 77 5 No primary G-CSF; prophylactic antibiotics 72 0 FN not defined in terms of ANC
Pettengell 1992[28] RCT, OL Aggressive NHL Any stage Age range 16-71 VAPEC-B 11 1 week (differs alternate weeks) Filgrastim primary: 230 ug/m2/d from day 2 up to 14d or until ANC = 10 × 109/l; prophylactic antibiotics 41 12 No primary G-CSF; prophylactic antibiotics 39 0 Fever + ANC < 1 × 109/l
Fossa 1998[32] RCT, phase III, OL Germ cell cancer Metastatic, poor-prognosis Age range 15-65 BEP/EP or BOP/VIP-B 6 3 weeks or 10 d Filgrastim primary: 5 ug/kg/d from day 3 or 6 129 7 or 14 No primary G-CSF 130 0 FN not defined in terms of ANC
Lenograstim vs. no primary G-CSF               
Chevallier 1995[9] RCT, DB Breast cancer, inflammatory Non-metastatic Age range 23-65 FEC-high-dose 4 3 weeks Lenograstim primary: 5 ug/kg/d from day 6 61 10 Placebo primary 59 0 Fever + ANC < 1 × 109/l
Gisselbrecht 1997[34] RCT, DB Aggressive NHL Any stage Age range 15-55 LNH-87 (LNH-84 + randomization to anthracyclines) 4 2 weeks Lenograstim primary: 5 ug/kg/d from day 6 82 8 Placebo primary 80 0 Fever + ANC < 1 × 109/l
Bui 1995[10] RCT, DB Soft tissue sarcoma Metastatic or locally advanced Age range 21-69 MAID 6 (FN reported cycle 1 only) 3 weeks Lenograstim primary: 5 ug/kg/d from day 4 up to 14d or until ANC = 30 × 109/l 22 10 to 14 Placebo primary; secondary G-CSF 26 0 Fever + ANC < 1 × 109/l
Gebbia 1994[35] RCT, DB Various Advanced Age range 40-75 Various Various Various Lenograstim primary: 5 ug/kg/d 23 ≥ 7d Placebo primary 28 0 Fever + ANC < 1 × 109/l
Gebbia 1993[36] RCT, DB Various Advanced Age range 38-66 Various Various Various Lenograstim primary: 5 ug/kg/d 43 7 to 10 Placebo primary 43 0 Fever + ANC < 1 × 109/l
Pegfilgrastim vs. 10- or 11-day filgrastim               
Green 2003[7] RCT, phase III, DB Breast cancer 28% stage II, 27% stage III, 45% stage IV Mean age 52, range 30-75 Doxorubicin 60 mg/m2/docetaxel 75 mg/m2 4 3 weeks Pegfilgrastim primary: 6 mg day 2; then placebo up to 14d 77 1 Filgrastim primary: 5 ug/kg, from day 2 up to 14d or until ANC = 10 × 109/l 75 11 (median) Fever + ANC < 0.5 × 109/l
Holmes 2002: phase III[8] RCT, phase III, DB Breast cancer High-risk stage II, III or IV. 37% stage IV Mean age 51 Doxorubicin 60 mg/m2/docetaxel 75 mg/m2 4 3 weeks Pegfilgrastim primary: 100 ug/kg day 2; then placebo up to 14d 149 1 Filgrastim primary: 5 ug/kg, from day 2 up to 14d or until ANC = 10 × 109/l 147 11 (mean) Fever + ANC < 0.5 × 109/l
Holmes 2002: phase II[37] RCT, phase II, DF Breast cancer High-risk stage II, III or IV. 30% stage IV Mean age 49 Doxorubicin 60 mg/m2/docetaxel 75 mg/m2 4 3 weeks Pegfilgrastim primary: 100 ug/kg day 2 (other dose groups not included here) 46 1 Filgrastim primary: 5 ug/kg, from day 2 up to 14d or until ANC = 10 × 109/l 25 10.6; 10.2; 10.4; 11.0 (mean in cycles 1-4) Fever + ANC < 0.5 × 109/l
Grigg 2003[38] RCT, phase II, OL, DF NHL Any stage Age ≥ 60. Mean 68, range 60-82 CHOP 6 3 weeks Pegfilgrastim primary: 100 ug/kg day 2 (other dose groups not included here) 14 1 Filgrastim primary: 5 ug/kg, from day 2 up to 14d or until ANC = 10 × 109/l 13 10 (mean) Fever + ANC < 0.5 × 109/l
Vose 2003[39] RCT, phase II, OL NHL (n = 56) or HL (n = 4) Relapsed or refractory Mean age 49. 85% < 65 ESHAP 4 (FN reported cycles 1 & 2 only) 3 weeks Pegfilgrastim primary: 100 ug/kg day 2 29 1 Filgrastim primary: 5 ug/kg, from day 2 up to 12d or until ANC = 10 × 109/l 31 11 (median) Fever + ANC < 0.5 × 109/l
  1. a Studies added as a result of updated search. b G-CSF strategy: Primary prophylaxis is in all cycles. Secondary prophylaxis is in all cycles following FN, or following FN or neutropenia, or at physician's discretion (as noted for individual studies). ANC = absolute neutrophil count; DB = double-blind; DF = dose-finding; HL = Hodgkin's lymphoma; NHL = non-Hodgkin's lymphoma; OL = open-label; SCLC = small-cell lung cancer. Chemotherapy regimens used: BEP/EP = etoposide 100 mg/m2, cisplatin 20 mg/m2, plus or minus bleomycin 30 U. BOP/VIP-B = bleomycin 30 U, vincristine 2 mg, cisplatin 20-50 mg/m2/etoposide 100 mg/m2, ifosfamide 1000 mg/m2. CDE = cyclophosphamide 1 g/m2, doxorubicin 45-50 mg/m2, etoposide 100-120 mg/m2. CHOP = cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, vincristine 1.4 mg/m2, prednisolone 100 mg days 1-5. CNOP = cyclophosphamide 750 mg/m2, mitoxantrone 10 mg/m2, vincristine 1.4 mg/m2, prednisolone 50 mg/m2 days 1-5. ESHAP = etoposide 40 mg/m2, methylprednisolone 500 mg, cisplatin 25 mg/m2/d, cytarabine 2000 mg/m2. FEC-100 = 5-fluorouracil 500 mg/m2, epirubicin 100 mg/m2, cyclophosphamide 500 mg/m2. FEC-high-dose = 5-fluorouracil 750 mg/m2, epirubicin 35 mg/m2, cyclophosphamide 400 mg/m2. FOIL = 5-FU, oxaliplatin, irinotecan, leucovorin. FOLFIRI = 5-FU, irinotecan, leucovorin. FOLFOX = 5-FU, oxaliplatin, leucovorin. LNH-87 = cyclophosphamide 1200 mg/m2 day 1, vindesine 2 mg/m2 days 1 & 5, bleomycin 10 mg days 1 & 5, prednisolone 60 mg/m2 days 1-5, methotrexate 15 mg, with either doxorubicin 75 mg/m2 or mitoxantrone 12 mg/m2 day 1. MAID = mesna, doxorubicin, ifosfamide, dacarbazine. R-CHOP = CHOP plus rituximab. TAC = doxorubicin 50 mg/m2, cyclophosphamide 500 mg/m2, docetaxel 75 mg/m2. VAPEC-B = vincristine 1.4 mg/m2, doxorubicin 35 mg/m2 prednisolone 50 mg/d (then tapered), etoposide 100 mg/m2, cyclophosphamide 350 mg/m2, bleomycin 10 mg/m2. VNCOP-B = vincristine 2 mg, mitoxantrone 10 mg/m2, cyclophosphamide 300 mg/m2, etoposide 150 mg/m2, prednisone 40 mg, bleomycin 10 mg/m2.