Table 1 Literature search results – included studies
Study | Patients enrolled | Study design | Data source | Year | Location | Comparator | Cancer type | Chemotherapy regimen | Study objectives |
|---|---|---|---|---|---|---|---|---|---|
Balducci [19] | N = 199 | Retrospective analysis | Five Amgen-sponsored pegfilgrastim clinical trials: 1. NCT00117897 2. Amgen study number 20010203 3. Amgen study number 990118 4. NCT002771605. NCT00115193 | n/a (combined analyses) | n/a (combined analyses) | Q3W regimen | NHL | CHOP or R-CHOP | Examine the impact of pegfilgrastim as primary prophylaxis on maintaining RDI in patients with NHL treated with CHOP-based chemotherapy Evaluate the incidence of chemotherapy dose delays, dose reductions, treatment discontinuation, and AEs leading to dose alteration (i.e., dose reduction or dose delay) or treatment discontinuation |
Bozzoli [20] | N = 51 | Prospective, randomized study | n/a | Jan 2006–Sep 2011 | Europe (Italy) | Filgrastim | DLBCL | R-CHOP-14 | The dose intensity of chemotherapy during the first four R-CHOP-14 cycles Secondary endpoints: incidence of adverse reactions, FN, and hospitalization, and the response to chemotherapy |
Donkor [21] | N = 51 | Single-institution, retrospective cohort | Cancer center of a 900-bed academic medical center | Jun 2013–Dec 2015 | n/a | CSF or none | Colon, rectal, appendix, gastric, pancreatic, esophageal, small bowel | FOLFOX ± MAB, FOLFIRI ± MAB, FOLFIRINOX, or other 5-FU infusion-containing regimens ± MAB | Assess the number of chemotherapy cycles with neutropenia, FN, and/or hospitalizations in cycles in which pegfilgrastim was administered < 14 days from the next chemotherapy dose |
Dragnev [22] | N = 35 | Single-institution, open-label, dose-escalation, phase 1 trial | n/a | Apr 2000–Aug 2004 | USA | Filgrastim | Solid tumors with a preponderance of GI cancer and pancreaticobiliary tumors | Gemcitabine 3000 mg/m2 and increasing doses of docetaxel (55 mg/m2 in 10 mg/m2 increments) every 14 days | Establish the maximum tolerated dose of docetaxel given with gemcitabine 3000 mg/m2 on a Q2W schedule with growth factor support Determine the feasibility of using filgrastim or pegfilgrastim to increase the dose intensity of Q2W docetaxel and gemcitabine Secondary endpoints: safety of administration of pegfilgrastim with a Q2W chemotherapy regimen; exploratory comparison between the efficacy and safety of filgrastim and pegfilgrastim with docetaxel and gemcitabine every 14 days |
Hecht [23] | N = 252 | 1:1 randomized, double-blind, placebo-controlled, phase 2 trial | n/a | Feb 2003–Mar 2008 | USA | Placebo | CRC | Patients received one of the following three Q2W chemotherapy regimens: FOLFOX-4: oxaliplatin 85 mg/m2 on day 1, LV 200 mg/m2 IV on days 1 and 2, 5-FU 400 mg/m2 bolus, then 600 mg/m2 administered over 22 h on both days 1 and 2 FOLFIRI: irinotecan 180 mg/m2 on day 1, LV 200 mg/m2 IV on days 1 and 2, 5-FU 400 mg/m2 bolus, then 600 mg/m2 administered over 22 h on both days 1 and 2 FOIL: irinotecan 175 mg/m2 IV on day 1, oxaliplatin 100 mg/m2 IV on day 1, LV 200 mg/m2 IV on day 1, 5-FU 3.0 g/m2 IV administered over 48 h starting on day 1 | Incidence of grade 3/4 neutropenia (ANC < 1.0 × 10 × 9/L) during the first four cycles of chemotherapy Secondary endpoints: incidence of grade 3/4 FN, neutropenia-related hospitalization rate and related antibiotic use, incidence of chemotherapy dose delays and/or dose reductions because of a neutropenic event, ORR, and incidence of AEs |
Hendler [24] | N = 231 | Prospective, non-randomized trial | CALGB study | Jun 2003–Jan 2009 | n/a | Filgrastim | Breast cancer | Four cycles of doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2; AC) once Q2W for four cycles, followed by weekly paclitaxel (80 mg/m2) for 12 weeks | Evaluate the four different schedules of growth factor support administration with regard to the occurrence of FN, hospitalization events, treatment delays, and other hematological toxicities |
Kourlaba [25] | N = 1058 | Retrospective cohort | Two randomized trials (HE10/00 and HE10/05) and an observational study (HE10/08) | n/a | Data analyzed in Greece | Filgrastim | Breast cancer | For HE10/00: patients randomized to receive either epirubicin (E, 110 mg/m2) Q2W for three cycles, followed by three cycles of paclitaxel (T, 250 mg/m2) Q2W, followed by three cycles of CMF (cyclophosphamide 840 mg/m2, methotrexate 57 mg/m2 and 5-FU 840 mg/m2) Q2W (E-T-CMF) for group A or E (83/m2) in combination with T (187/m2) Q3W for four cycles, followed by CMF as above Q2W for three cycles (ET-CMF) for group B For HE10/05: patients were randomized to receive E-T-CMF as in group A of protocol HE10/00 for group A or E (110 mg/m2) Q2W for three cycles, followed by three cycles of CMF (cyclophosphamide 840 mg/m2, methotrexate 57 mg/m2 and 5-FU 840 mg/m2) Q2W followed 3 weeks later by nine weekly cycles of docetaxel 35 mg/m2 (E-CMF-DOC) for group B or E-CMF (as previously described in group B) followed 3 weeks later by nine weekly cycles of paclitaxel 80 mg/m2 for group For HE10/08: 110 mg/m2 Q2W for three cycles, followed by three cycles of paclitaxel (T, 200 mg/m2) Q2W followed by three cycles of CMF (cyclophosphamide 600 mg/m2, methotrexate 45 mg/m2 and 5-FU 600 mg/m2) Q2W (E-T-CMF) | Primary endpoints were FN, severe (grade 3, 4) neutropenia, dose reduction (>  10% reduction of the dose planned), and treatment delay (dose given > 2 days later) |
Kurbacher [26] | N = 53 | Retrospective analysis | Not reported | n/a | n/a | Lipegfilgrastim | Breast or gynecologic cancer | 1–4 ddCtx | Use of the long-acting G-CSFs as FN primary prophylaxis in the clinical routine |
Lane [27] | N = 81 | Multicenter, retrospective analysis | Audit from databases of Australian hospitalsa | Jan 1999–Jul 2005 | Australia | Filgrastim | ALL or NHL | Hyper-CVAD chemotherapy | Duration of grade 4 neutropenia (ANC < 500/μL) |
Lugtenburg [28] | N = 1113 | Multicenter, retrospective/prospective, observational study | IMPACT NHL study (NCT00903812) | Patients had to have started chemotherapy after Jan 1, 2005 | Europe and Australia | CHOP every 21 days | DLBCL | Rituximab (R-CHOP) every 14 days or every 21 days | Evaluate the impact of age group (younger, <  65 years old; older, ≥ 65 years old) on the assessment of FN risk, G-CSF use patterns, incidence of FN, and chemotherapy delivery in patients with DLBCL receiving an R-CHOP regimen Outcome measures: the proportion of patients in whom investigators assessed risk of FN at ≥20% and who received primary prophylaxis with G-CSF, as well as type of G-CSF, rate of FN, chemotherapy relative dose intensity ≥90%, chemotherapy dose delays, and chemotherapy dose reductions |
Ng [29] | N = 132 | Single-center, observational, retrospective cohort | National Cancer Centre Singapore, patients identified through the Singapore Lymphoma Registry | Jan 2007–May 2009 | Singapore | CHOP every 21 days | NHL | CHOP every 21 days (standard dose regimen, designated as CHOP-21) or every 14 days (dose-dense regimen designated as CHOP-14) | Identify clinical characteristics of patients on CHOP-based chemotherapy that would predispose them to develop breakthrough FN and provide descriptive data on the incidence of breakthrough FN among patients with lymphoma |
Pinter [30] | N = 845 | Phase 3, double-blind randomized trial | Pegfilgrastim and Anti-VEGF Evaluation Study (PAVES) | Nov 2009–Jan 2012 | North America and rest of worldb | Placebo | Locally advanced or metastatic adenocarcinoma of the colon or rectum | Physicians predetermined the chemotherapy regimen that was included with bevacizumab (5 mg/kg intravenous infusion on day 1 of each 14-day cycle), either FOLFOX (FOLFOX4, FOLFOX6 or modified mFOLFOX6) or FOLFIRI (FOLFIRI [Douillard] or FOLFIRI) | The incidence of grade 3/4 FN during the first four cycles Other endpoints: the incidence of grade 4 FN, grade 3/4 neutropenia, grade 4 neutropenia, CSF use, RDI, dose delays, and dose reductions during the four treatment cycles and ORR, OS, and PFS during the LTFU period |
Skarlos [31] | N = 214 | Retrospective (non-randomized), matched case-control study | Two randomized trials (HE10/00 and HE10/05) from the Hellenic Cooperative Oncology Group | Not reported | Data analyzed in Greece | Filgrastim on day 2–10 following chemotherapy | Histologically confirmed epithelial breast cancer | ET-CMF: Epirubicin (E) every 2 weeks for 3 cycles followed by 3 cycles of Paclitaxel (T) every 2 weeks, followed by 3 cycles of CMF (cyclophosphamide, methotrexate, and 5-Fluorouracil) every 2 weeks | Proportion of patients with early breast cancer who developed FN among those who received filgrastim or pegfilgrastim support during adjuvant treatment with dose-dense sequential therapy Secondary endpoints: the incidence of severe (grade 3, 4) neutropenia and the ability to receive chemotherapy as planned (≤ 90% of the dose planned and no dose given > 2 days later) |