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