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PubMed1998

Randomized multicentre trial of filgrastim as an adjunct to combination chemotherapy for Hodgkin's disease. West of Scotland Lymphoma Group.

This study was intended to ascertain whether the adjunctive administration of filgrastim (r metHuG-CSF, Amgen) would influence the dose intensity of chemotherapy or the morbidity of myelosuppression in patients receiving MOPP or MOPP/EVAP hybrid chemotherapy for Hodgkin's disease. In a prospective randomized trial, two regimens for the treatment of Hodgkin's disease were compared. The substudy described here randomized patients receiving either regimen to receive filgrastim on the days when chemotherapy was not administered. During chemotherapy, parameters of myelosuppression were documented, including dose delays, the severity and duration of neutrophil and platelet nadirs, infective episodes, and resulting hospital admissions. In the MOPP arm, 13/25 eligible patients, and, in the MOPP/EVAP arm, 12/22 eligible patients, received filgrastim. The use of filgrastim made no statistically significant difference to the administered dose intensity for either MOPP (P = 0.57, 95% confidence interval (CI) 15-point increase to 8-point reduction) or MOPP/EVAP (P = 0.53; 95% CI 7-point increase to 11-point reduction). In patients receiving MOPP, filgrastim reduced the median duration of leucopenia (P = 0.007) and the severity of the white blood cell nadir (P = 0.036); however, no statistically significant effect (at the 5% level) was seen in platelet or haemoglobin nadirs, the number of days of in-patient hospitalization, the number of admissions for infective complications, the incidence, grade or duration of infections, or the incidence of febrile neutropenia. In patients receiving MOPP/EVAP, filgrastim had no significant effect on the duration or depth of leucopenia but was associated with a reduction in the median haemoglobin (P = 0.002) and platelet nadirs (P = 0.015). No effect on the above listed sequelae of myelosuppression was influenced by the administration of filgrastim. This study, although small, suggests that the routine use of filgrastim, aimed at influencing the administered dose intensity of conventional dose chemotherapy in Hodgkin's disease, is not warranted.

Adolescent↗
PubMed1998

A randomised, blinded, placebo-controlled, dose escalation study of the tolerability and efficacy of filgrastim for haemopoietic stem cell mobilisation in patients with severe active rheumatoid arthritis.

Autologous haemopoietic stem cell transplantation (HSCT) represents a potential therapy for severe rheumatoid arthritis (RA). As a prelude to clinical trails, the safety and efficacy of haemopoietic stem cell (HSC) mobilisation required investigation as colony-stimulating factors (CSFs) have been reported to flare RA. A double-blind, randomised placebo-controlled dose escalation study was performed. Two cohorts of eight patients fulfilling strict eligibility criteria for severe active RA (age median 40 years, range 24-60 years; median disease duration 10.5 years, range 2-18 years) received filgrastim (r-Hu-methionyl granulocyte(G)-CSF) at 5 and 10 microg/kg/day, randomised in a 5:3 ratio with placebo. Patients were unblinded on the fifth day of treatment and those randomised to filgrastim underwent cell harvesting (leukapheresis) daily until 2 x 10(6)/kg CD34+ cells (haemopoietic stem and progenitor cells) were obtained. Patients were assessed by clinical and laboratory parameters before, during and after filgrastim administration. RA flare was defined as an increase of 30% or more in two of the following parameters: tender joint count, swollen joint count or pain score. Efficacy was assessed by quantitation of CD34+ cells and CFU-GM. One patient in the 5 microg/kg/day group and two patients in the 10 microg/kg/day group fulfilled criteria for RA flare, although this did not preclude successful stem cell collection. Median changes in swollen and tender joint counts were not supportive of filgrastim consistently causing exacerbation of disease, but administration of filgrastim at 10 microg/kg/day was associated with rises in median C-reactive protein and median rheumatoid factor compared with placebo. Other adverse events were well recognised for filgrastim and included bone pain (80%) and increases in alkaline phosphatase (four-fold) and lactate dehydrogenase (two-fold). With respect to efficacy, filgrastim at 10 microg/kg/day was more efficient with all patients (n = 5) achieving target CD34+ cell counts with a single leukapheresis (median = 2.8, range = 2.3-4.8 x 10(6)/kg, median CFU-GM = 22.1, range = 4.2-102.9 x 10(4)/kg), whereas 1-3 leukaphereses were necessary to achieve the target yield using 5 microg/kg/day. We conclude that filgrastim may be administered to patients with severe active RA for effective stem cell mobilisation. Flare of RA occurs in a minority of patients and is more likely with 10 than 5 microg/kg/day. However, on balance, 10 microg/kg/day remains the dose of choice in view of more efficient CD34+ cell mobilisation.

Adult↗
PubMed2003

Open-label, randomized study of pegfilgrastim vs. daily filgrastim as an adjunct to chemotherapy in elderly patients with non-Hodgkin's lymphoma.

Pegfilgrastim is composed of the protein filgrastim to which a 20-kDa polyethylene glycol (PEG) is covalently bound at the N-terminal residue resulting in decreased renal clearance and increased plasma half-life compared with filgrastim. This open-label, randomized, phase 2 study compared two doses of single administration pegfilgrastim (60 and 100 microg/kg) with daily doses of filgrastim (5 microg/kg/day) or no cytokine treatment after standard CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) chemotherapy for non-Hodgkin's lymphoma in 50 elderly patients. The primary endpoint was the duration of grade 4 (severe) neutropenia (absolute neutrophil count < 0.5 x 10(9)/l) in cycle 1. Duration of grade 4 neutropenia in cycle 1 was 2.2 (SD 1.2), 1.5 (SD 1.1), 0.8 (1.2) and 5.0 (2.0) days for patients who received pegfilgrastim 60 microg/kg, pegfilgrastim 100 microg/kg, filgrastim 5 microg/kg and no cytokine, respectively. The baseline characteristics of the pegfilgrastim and filgrastim groups were imbalanced with increased bone-marrow involvement and prior therapy in the former. When the treatment groups were balanced for these risk factors, duration of grade 4 neutropenia was comparable with 2.0 and 3.0 vs. 0.6 and 0.5 days for pegfilgrastim 100 microg/kg and filgrastim patients with and without these risk factors, respectively. The incidence of febrile neutropenia (defined as ANC < 0.5 x 10(9)/l and temperature > 38.2degrees C) was low (10% of patients). Pegfilgrastim was well tolerated with a safety profile similar to daily filgrastim. Once per chemotherapy cycle administration of pegfilgrastim was comparable to filgrastim in this clinical setting.

Aged↗
PubMed2003

A randomized double-blind multicenter phase III study of fixed-dose single-administration pegfilgrastim versus daily filgrastim in patients receiving myelosuppressive chemotherapy.

BACKGROUND: We evaluated the efficacy of a single fixed 6 mg dose of pegfilgrastim (a pegylated version of filgrastim) per cycle of chemotherapy, compared with daily administration of filgrastim, in the provision of neutrophil support. PATIENTS AND METHODS: Patients (n = 157) were randomized to receive either a single 6 mg subcutaneous (s.c.) injection of pegfilgrastim or daily 5 mg/kg s.c. injections of filgrastim, after doxorubicin and docetaxel chemotherapy (60 mg/m(2) and 75 mg/m(2), respectively). Duration of grade 4 neutropenia, depth of neutrophil nadir, incidence of febrile neutropenia, time to neutrophil recovery and safety information were recorded. RESULTS: A single 6 mg injection of pegfilgrastim was as effective as daily injections of filgrastim for all efficacy measures for all cycles. The mean duration of grade 4 neutropenia in cycle 1 was 1.8 and 1.6 days for the pegfilgrastim and filgrastim groups, respectively. Results for all efficacy end points in cycles 2-4 were consistent with the results from cycle 1. A trend towards a lower incidence of febrile neutropenia was noted across all cycles with pegfilgrastim compared with filgrastim (13% versus 20%, respectively). A single fixed dose of pegfilgrastim was as safe and well tolerated as standard daily filgrastim. CONCLUSIONS: A single fixed dose of pegfilgrastim administered once per cycle of chemotherapy was comparable to multiple daily injections of filgrastim in safely providing neutrophil support during myelosuppressive chemotherapy. Pegfilgrastim may have utility in other clinical settings of neutropenia.

Adult↗
PubMed2000

Filgrastim as an alternative to donor leukocyte infusion for relapse after allogeneic stem-cell transplantation.

PURPOSE: Donor leukocyte infusion (DLI) effectively treats relapse after allogeneic stem-cell transplantation (alloSCT), but the response may require several months and may be associated with significant toxicity. Filgrastim has also been observed to effectively treat leukemic relapse after alloSCT. A retrospective analysis was performed to determine the effectiveness of filgrastim in treating relapses after alloSCT. PATIENTS AND METHODS: Fourteen patients with hematologic malignancies were treated with filgrastim at relapse after alloSCT. Filgrastim was given at 5 mcg/kg/d subcutaneously for 21 consecutive days. Response was evaluated at 7 days after completion of filgrastim. Immunosuppressants, if present, were rapidly tapered to complete discontinuation at the time of relapse. RESULTS: Three patients were not assessable for response because additional therapy was necessary before completion of filgrastim. Six patients (43%) achieved a complete response on an intent-to-treat basis. When response was evaluated based on relapse type, three of four cytogenetic relapses, two of three morphologic relapses, and one of four hematologic relapses achieved a complete remission. Two responses were observed in patients who were completely off of any immunosuppression at the time of relapse. Six patients developed chronic graft-versus-host disease. The event-free and overall survival rates for all 14 patients are 43% and 73%, respectively. CONCLUSION: The use of filgrastim with rapid discontinuation of immunosuppression results in response rates that are similar to results using DLI. Filgrastim could be considered as an alternative or an adjunct to DLI for relapses after alloSCT.

Adult↗
PubMed2002

Blinded, randomized, multicenter study to evaluate single administration pegfilgrastim once per cycle versus daily filgrastim as an adjunct to chemotherapy in patients with high-risk stage II or stage III/IV breast cancer.

PURPOSE: This multicenter, randomized, double-blind, active-control study was designed to determine whether a single subcutaneous injection of pegfilgrastim (SD/01, sustained-duration filgrastim; 100 microg/kg) is as safe and effective as daily filgrastim (5 microg/kg/d) for reducing neutropenia in patients who received four cycles of myelosuppressive chemotherapy. PATIENTS AND METHODS: Sixty-two centers enrolled 310 patients who received chemotherapy with docetaxel 75 mg/m(2) and doxorubicin 60 mg/m(2) on day 1 of each cycle for a maximum of four cycles. Patients were randomized to receive on day 2 either a single subcutaneous injection of pegfilgrastim 100 microg/kg per chemotherapy cycle (154 patients) or daily subcutaneous injections of filgrastim 5 microg/kg/d (156 patients). Absolute neutrophil count (ANC), duration of grade 4 neutropenia, and safety parameters were monitored. RESULTS: One dose of pegfilgrastim per chemotherapy cycle was comparable to daily subcutaneous injections of filgrastim with regard to all efficacy end points, including the duration of severe neutropenia and the depth of ANC nadir in all cycles. Febrile neutropenia across all cycles occurred less often in patients who received pegfilgrastim. The difference in the mean duration of severe neutropenia between the pegfilgrastim and filgrastim treatment groups was less than 1 day. Pegfilgrastim was safe and well tolerated, and it was similar to filgrastim. Adverse event profiles in the pegfilgrastim and filgrastim groups were similar. CONCLUSION: A single injection of pegfilgrastim 100 microg/kg per cycle was as safe and effective as daily injections of filgrastim 5 microg/kg/d in reducing neutropenia and its complications in patients who received four cycles of doxorubicin 60 mg/m(2) and docetaxel 75 mg/m(2).

Aged↗
PubMed2006

Are shorter courses of filgrastim prophylaxis associated with increased risk of hospitalization?

BACKGROUND: In clinical trials in patients receiving myelosuppressive chemotherapy, 10-11 days of prophylaxis with filgrastim has been found to reduce the incidence of febrile neutropenia. In clinical practice, however, many patients receive shorter courses of therapy, even though the effectiveness of this regimen is unknown. OBJECTIVE: To examine the relationship between duration of filgrastim prophylaxis and risk of hospitalization in patients receiving chemotherapy for non-Hodgkin's lymphoma (NHL), breast cancer, or lung cancer. METHODS: Using a large, automated, US healthcare claims database, we identified all adults who received chemotherapy for NHL, breast cancer, or lung cancer between 1998 and 2002. For these patients, we identified their first course of chemotherapy and each unique cycle within that course. We then focused attention on all patient cycles in which filgrastim was administered on or before cycle day 5 (filgrastim prophylaxis). Pooling all such cycles, we examined the relationship between duration of filgrastim prophylaxis and risk of hospitalization for neutropenia or infection and risk of hospitalization for any reason, using generalized estimating equations. RESULTS: Mean +/- SD duration of filgrastim prophylaxis was 6.5 +/- 3.1 days across 332 cycles for 133 NHL patients, 6.1 +/- 2.9 days across 482 cycles for 205 breast cancer patients, and 4.3 +/- 3.1 days across 522 cycles for 260 lung cancer patients. In multivariate analyses, risk of hospitalization for neutropenia or infection was found to decline with each additional day of filgrastim prophylaxis for patients with NHL (OR 0.81; p = 0.003), breast cancer (OR 0.77; p = 0.001), and lung cancer (OR 0.91; p = 0.084). Risk reductions with each additional day of prophylaxis ranged from 15% to 19% for patients with NHL, 17% to 23% for those with breast cancer, and 8% to 9% for those with lung cancer. Similar reductions in risk were noted for all-cause hospitalization. CONCLUSIONS: Among patients with NHL, breast cancer, or lung cancer, shorter courses of filgrastim prophylaxis may increase the risk of hospitalization.

Aged↗
PubMedDate not supplied

Days of prophylactic filgrastim use to reduce febrile neutropenia in patients with non-Hodgkin's lymphoma treated with chemotherapy.

BACKGROUND: Filgrastim prophylaxis lessens the occurrence of febrile neutropenia in patients with non-Hodgkin.s lymphoma (NHL) treated with chemotherapy, but differences in days of therapy and mode (primary or secondary) of prophylaxis may affect clinical outcomes. OBJECTIVE: To describe the patterns of use of filgrastim prophylaxis, especially days of therapy and mode, and the possible associated incidence of febrile neutropenia in patients treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy. METHODS: Using medical records from the Oncology Practice Pattern Study in patients treated between 1991 and 1999 at 12 sites in the United States, we studied patients with intermediate-grade NHL treated with first-line CHOP chemotherapy and prophylactic filgrastim. The number of days of prophylactic filgrastim use, mode of prophylaxis, and incidence of febrile neutropenia were evaluated. The cycles were stratified into 2 groups based on days of filgrastim prophylaxis (<7 days [Group 1] and > or = 7 days [Group 2]). RESULTS: One hundred seventy patients were treated with 652 cycles of CHOP chemotherapy with filgrastim prophylaxis. The mean days of filgrastim prophylaxis was 9.5 days (95% confidence interval [CI], 9.3-9.7 days) across all cycles, 4.7 days (95% CI, 4.5-5.0 days) across Group 1 cycles (n=73), and 10.1 days (95% CI, 9.9-10.3 days) across Group 2 cycles (n=579). Thirty-seven percent of patients were treated with primary prophylaxis; 94% of these patients. cycles were Group 2 cycles. The incidence of febrile neutropenia was 3.6% and 7.7% across cycles in patients receiving primary versus secondary prophylaxis, respectively. In patients treated with secondary prophylaxis, the incidence was 16.7% and 6.1% in Group 1 and Group 2 cycles, respectively. Multiple logistic regression modeling indicated that a lower risk of febrile neutropenia was associated with primary prophylaxis (mainly Group 2) (odds ratio [OR] 0.3; 95% CI, 0.1-0.6) and secondary prophylaxis in Group 2 (OR 0.4; 95% CI, 0.2-0.8), and lower body surface area was associated with a greater risk of febrile neutropenia (OR 1.8; 95% CI, 1.1-3.0). CONCLUSION: Primary prophylaxis with filgrastim (mainly Group 2) and secondary prophylaxis in Group 2 (mean 10.1 days) may be associated with a lower incidence of febrile neutropenia than secondary prophylaxis in Group 1.

Aged↗
PubMed1994

Filgrastim. A review of its pharmacological properties and therapeutic efficacy in neutropenia.

Filgrastim, a recombinant human granulocyte colony-stimulating factor (G-CSF), has identical biological activity to that of endogenous human G-CSF, but differs in that it contains an N-terminal methionine residue and is not glycosylated. It principally stimulates activation, proliferation and differentiation of neutrophil progenitor cells and has been evaluated in the treatment of patients with various neutropenic conditions, both iatrogenic and disease-related. Two comparative studies have demonstrated that prophylactic administration of filgrastim 230 micrograms/m2/day significantly reduces the incidence, duration and severity of neutropenia in patients with previously untreated small-cell lung cancer receiving standard-dose chemotherapy with CDE (cyclophosphamide, doxorubicin plus etoposide). Concomitant with the amelioration of neutropenia, the incidence of febrile neutropenia was significantly reduced by 50% and there were 35 and 50% decreases in hospitalisation rates and intravenous antibiotic requirements. Since not all patients receiving standard-dose chemotherapy are at risk of infectious complications, prophylactic filgrastim use may be reserved for those patients who have developed febrile neutropenia during a previous cycle of the same regimen. This strategy may prove less costly, although potential savings must be weighed against a greater risk of patient morbidity and reduced quality of life. When combined with standard intravenous antibiotic therapy, filgrastim further decreases morbidity in patients with established febrile neutropenia and may have a positive impact on overall treatment costs by shortening the length of hospitalisation. Attention is focused on the use of haematopoietic growth factors to support dose-intensification of chemotherapy with a view to improving treatment outcomes in patients with chemo-responsive tumours. Filgrastim, used alone, permits modest increases in dose-intensity and/or dose-escalation of some standard-dose chemotherapy regimens. Moreover, the drug has proven useful as an adjunct to myeloablative chemotherapy followed by stem cell rescue with autologous bone marrow transplantation and/or peripheral blood progenitor cells. However, the impact of these dose-intensification approaches on survival remains to be determined in well-controlled clinical studies. Filgrastim is effective in increasing the neutrophil count and decreasing morbidity in patients with severe chronic neutropenia, including Kostmann's syndrome, and in idiopathic and cyclic neutropenia. In addition, filgrastim has accelerated neutrophil recovery in patients with idiosyncratic drug-induced agranulocytosis. Available data indicate that filgrastim is generally well tolerated. The most frequent adverse reaction is mild to moderate medullary bone pain, reported by approximately 20% of patients, although this can generally be controlled using simple analgesics without the need to discontinue treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1999

A randomized phase 3 study of peripheral blood progenitor cell mobilization with stem cell factor and filgrastim in high-risk breast cancer patients.

This randomized study compared the number of leukaphereses required to collect an optimal target yield of 5 x 10(6) CD34(+) peripheral blood progenitor cells/kg, using either stem cell factor (SCF) at 20 micrograms/kg/d in combination with Filgrastim at 10 micrograms/kg/d or Filgrastim alone at 10 micrograms/kg/d, from 203 patients with high-risk stage II, III, or IV breast cancer. Leukapheresis began on day 5 of cytokine administration and continued daily until the target yield of CD34(+) cells had been reached or a maximum of 5 leukaphereses performed. By day 5 of leukapheresis, 63% of the patients treated with SCF plus Filgrastim (n = 100) compared with 47% of those receiving Filgrastim alone (n = 103) reached the CD34(+) cell target yield. There was a clinically and statistically significant reduction (P <.05) in the number of leukaphereses required to reach the target yield for the patients receiving SCF plus Filgrastim (median, 4 leukaphereses) compared with patients receiving Filgrastim alone (median, 6 or more leukapherses; ie, <50% of patients reached the target in 5 leukaphereses). All patients receiving SCF were premedicated with antihistamines, albuterol, and pseudoephedrine. Treatment was safe, generally well tolerated, and not associated with life-threatening or fatal toxicity. In conclusion, SCF plus Filgrastim is a more effective peripheral blood progenitor cell (PBPC)-mobilization regimen than Filgrastim alone. In addition to the potential for reduced leukapheresis-related morbidity and costs, SCF offers additional options for obtaining cells for further graft manipulation.

Adult↗
PubMedDate not supplied

Clinical trial of weekly intensive therapy with 5-fluorouracil on two different schedules combined with interferon alpha-2a and filgrastim in patients with advanced solid tumors: Eastern Cooperative Oncology Group Study P-Z991.

PURPOSE: The hematopoietic growth factor filgrastim has been shown to reduce both chemotherapy-induced myelosuppression and mucosal toxicities. The aim of this study was to conduct four separate pilot trials to determine the maximum-tolerated doses at which interferon alpha (IFN alpha) followed by 5-fluorouracil (5-FU) could be administered in combination with filgrastim support. PATIENTS AND METHODS: Patients were required to have a histologically documented solid tumor with either measurable or evaluable lesions. All patients were fully ambulatory; had adequate bone marrow, renal, and hepatic function; had recovered from surgery; and gave informed consent. Trials were conducted sequentially. In parts A and B, patients received 5-FU as a continuous intravenous infusion daily for 5 days, followed by weekly bolus therapy at the same dose. In parts C and D, patients received 5-FU as a weekly high-dose, 24-hour infusion. Interferon was administered immediately before the 5-FU three times a week. Filgrastim was administered at 5 micrograms/kg subcutaneously either four (parts A, B) or five (parts C, D) times a week. In part A, the starting doses were as follows: 5-FU, 750 mg/m2, and IFN alpha, 3 MU subcutaneously, and the IFN alpha was escalated between patient cohorts to a maximum of 9 MU. Part B used the dose of IFN alpha established from part A, and the 5-FU was escalated to the maximum-tolerated dose between patient cohorts. In part C, the starting dose of IFN alpha was 3 MU subcutaneously, and that of 5-FU, 2.6 g/m2, and the dose of IFN alpha was escalated to a maximum of 9 MU. In part D, the dose of IFN alpha was determined from part C, and the dose of 5-FU was escalated. The maximum tolerated dose was the highest dose at which three of three or five of six patients were able to tolerate therapy. RESULTS: There were 71 patients entered into the four parts of this trial. In part A (12 patients), the dose of IFN alpha, was escalated to 9 MU subcutaneously three times a week with only one patient experiencing dose-limiting toxicity. In part B (13 patients), the dose of 5-FU could not be escalated beyond 750 mg/m2 because of sepsis (one patient) and gastrointestinal hemorrhage (one patient). The predominant toxicities were diarrhea (46%), vomiting (23%), and mucositis (31%). In part C (24 patients), two patients experienced dose-limiting toxicities (staphylococcal sepsis [one patient] and neuropsychiatric [one patient]). The dose of IFN alpha was escalated to 9 MU. In part D (21 patients), the dose of 5-FU was escalated to 3.4 g/m2 administered weekly. No patients at this dose level experienced serious toxicities. At the next highest dose level, 3.6 g/m2, one patient each experienced gastrointestinal hemorrhage and diarrhea. There were no additive constitutional symptoms resulting from the combination of IFN alpha and filgrastim. In parts C and D, filgrastim could be administered 6 hours after the end of the 5-FU infusion without excessive myelosuppression. CONCLUSIONS: The addition of filgrastim allowed escalation of the dose of 5-FU on the weekly, high-dose schedule, but not on the weekly bolus schedule. IFN alpha and filgrastim can be administered without additive toxicities. Filgrastim can be safely administered < 24 hours after completion of the weekly, high dose 5-FU infusion.

Adult↗
PubMed1999

Two different schedules for integrating filgrastim as adjuvant therapy in the treatment of patients with advanced stage Hodgkin's lymphoma receiving MOPP/ABV hybrid chemotherapy.

PURPOSE: Management of advanced-stage Hodgkin's disease with a MOPP/ABV hybrid regimen (mechlorethamine, vincristine, procarbazine, prednisone, Adriamycin, bleomycin and vinblastine) has yielded a high complete response rate (75-85%). However, myelosuppression can limit delivery of treatment. Filgrastim has been shown to reduce chemotherapy-related neutropenia and allow for on-time administration of planned doses of chemotherapeutic agents. The objective of this study was to find the best way to integrate filgrastim with the MOPP/ABV hybrid regimen. METHODS: Enrolled in this study were 24 patients (aged 18-52 years) with newly diagnosed, histologically documented Hodgkin's disease. In schedule I, patients received filgrastim (5 microg/kg s.c. daily) beginning on day 9, 24 h after administration of ABV. In schedule II, patients received filgrastim concomitantly with procarbazine on days 2-7 (starting 24 h after day-1 MOPP administration and stopping 24 h before ABV administration) as well as after ABV beginning on day 9. Filgrastim after ABV administration was administered until two consecutive ANC readings of 10 x 10(9)/l were achieved. RESULTS: All patients were able to complete all six cycles of therapy. There was a trend to fewer dose reductions in schedule II (0.76%) as compared to schedule I (4.2%) with a P-value of 0.077 (chi-squared test). Specifically, 11.6% of MOPP courses and 5.5% of ABV courses were dose-reduced in schedule I versus 1.7% and 1.4%, respectively, in schedule II. CONCLUSION: In conclusion, filgrastim was effective in supporting the delivery of the MOPP/ABV chemotherapy. Concomitant administration of filgrastim with procarbazine (days 2-7) appears to be safe and allows the maximum dose intensity of this therapy.

Adolescent↗
PubMed2006

Long-term survival data from a phase 3 study of Filgrastim as an adjunct to chemotherapy in adults with de novo acute myeloid leukemia.

We previously reported the results of a double-blind, placebo-controlled study of Filgrastim in patients with de novo AML undergoing induction and consolidation chemotherapy. The study demonstrated that Filgrastim was effective and well tolerated and had no impact on complete remission or survival. We now report follow-up data on these patients, assessing long-term effects with emphasis on prognostic indicators. After a median follow-up of 7 years, 434 (83%) patients were dead, 73 (14%) were alive, and 14 (3%) were lost to follow-up. The proportions of deaths were similar in the Filgrastim (83%) and placebo (84%) groups. No differences in median time to death (1.04 years Filgrastim, 1.13 years placebo; P = 0.97) or median disease-free survival (0.86 years Filgrastim, 0.79 years placebo; P = 0.52) were evident. Proportional hazard modeling identified age, performance status, and French-American-British subtype as independent predictors for survival (P < 0.001, P = 0.005, and P = 0.036, respectively), whereas cytogenetic status was not (P = 0.118). Filgrastim had no effect on overall survival in any of these subgroup analyses as none of the treatment comparisons were statistically significant. These findings indicate that Filgrastim can be effectively used to support patients with AML undergoing induction and consolidation chemotherapy without worsening long-term disease outcome.

Acute Disease↗
PubMed2004

Increased replication of HIV-1 minor variants during hematopoietic stem-cell mobilization with filgrastim.

The hypothesis that filgrastim (r-met-huG-CSF) activates replication of minor variants of human inmmunodeficiency virus type 1 (HIV-1) was tested by analysis of plasma quasi-species composition in 7 subjects in whom plasma HIV-1 RNA had increased during filgrastim treatment. Inferred phylogenetic trees of env sequences from 3 subjects during filgrastim treatment contained unique intrasubject subclusters that shared a most recent common ancestor with the baseline HIV-1 quasi species. Genotypes in the unique subclusters were not detected before filgrastim treatment, yet they composed 40%-70% of the plasma quasi species during treatment. The minority variants that appeared in 1 subject were more distantly related to plasma quasi species present 5 years before filgrastim treatment than were the majority of the pretreatment plasma quasi species. These findings provide evidence that increased HIV-1 replication during filgrastim treatment was associated with activation of HIV-1 variants that, before filgrastim treatment, were minor components of the plasma quasi species.

Amino Acid Sequence↗
PubMed2002

Comparable efficacy and safety profiles of once-per-cycle pegfilgrastim and daily injection filgrastim in chemotherapy-induced neutropenia: a multicenter dose-finding study in women with breast cancer.

BACKGROUND: Neutropenia is common in patients receiving myelotoxic chemotherapy. Pegfilgrastim, a sustained-duration filgrastim is a once-per-cycle therapy for prophylactic neutrophil support. PATIENTS AND METHODS: Women, treated with four cycles of doxorubicin/docetaxel chemotherapy every 21 days, received pegfilgrastim or filgrastim 24 h after chemotherapy as a single subcutaneous injection per chemotherapy cycle (pegfilgrastim 30, 60 or 100 microg/kg) or daily subcutaneous injections (filgrastim 5 microg/kg/day). Safety, efficacy and pharmacokinetics were analyzed. RESULTS: The incidence of grade 4 neutropenia in cycle 1 was 95, 90 and 74%, in patients who received pegfilgrastim 30, 60 and 100 microg/kg, respectively, and 76% in patients who received filgrastim. Mean duration of grade 4 neutropenia in cycle 1 was 2.7,2 and 1.3 days for doses of pegfilgrastim, and 1.6 days for filgrastim. The pharmacokinetics of pegfilgrastim were non-linear and dependent on both dose and neutrophil count. Pegfilgrastim serum concentration was sustained until the neutrophil nadir occurred then declined rapidly as neutrophils started to recover, consistent with a self-regulating neutrophil-mediated clearance mechanism. The safety profiles of pegfilgrastim and filgrastim were similar. CONCLUSIONS: A single subcutaneous injection of pegfilgrastim 100 microg/kg provided neutrophil support and a safety profile comparable to daily subcutaneous injections of filgrastim during multiple chemotherapy cycles.

Adult↗
PubMed2000

Safety of granulocyte colony-stimulating factor (filgrastim) in intubated patients in the intensive care unit: interim analysis of a prospective, placebo-controlled, double-blind study.

OBJECTIVE: To investigate the safety of the granulocyte colony-stimulating factor filgrastim in the prevention of nosocomial infections in intubated patients in the intensive care unit (ICU), with special emphasis on the possible deleterious effect on acute respiratory distress syndrome (ARDS) and the development of multiple organ dysfunction (MOD). DESIGN: Predetermined, interim analysis of a prospective, randomized, placebo-controlled, double-blind trial. SETTING: University hospital medical-surgical ICU. PATIENTS: A total of 59 consecutive ICU patients, aged >18 yrs, admitted to the ICU no more than 12 hrs before the study, intubated because of ventilatory insufficiency no more than 48 hrs before the study, expected to stay in the ICU for >48 hrs, and had informed consent from the next relative. INTERVENTIONS: Patients were randomized to receive either placebo or 300 microg of filgrastim subcutaneously once daily for 7 days. MEASUREMENTS AND MAIN RESULTS: No significant differences were found in the number of patients developing ARDS (2 of 20 in the placebo group vs. 0 of 22 in the filgrastim group), disseminated intravascular coagulation (3 of 27 vs. 3 of 29), acute renal failure (1 of 27 vs. 1 of 23), or change in MOD. Data analysis showed nosocomial infections in 11 of 29 patients in the placebo group and in 7 of 30 patients in the filgrastim group (p = .266). The median (range) length of ICU stay was 8 (1-34) days in the placebo group and 6 days (1-28) in the filgrastim group. The day 28 mortality rate was 17% (5 of 29) in the placebo group and 13% (4 of 30) in the filgrastim group. No drug-related adverse events occurred. CONCLUSION: Filgrastim is safe in intubated ICU patients, with no excess risk for development of ARDS or MOD.

Adult↗
PubMed1999

A phase I study of paclitaxel and epirubicin, without and with filgrastim, for the treatment of platinum-resistant advanced ovarian cancer.

The aim of the study was to determine the maximum tolerated dose (MTD) of epirubicin combined with a fixed dose of paclitaxel, without and with support of filgrastim, in patients with platinum resistant or refractory ovarian cancer. Paclitaxel (150 mg/m2) and epirubicin (starting dose 90 mg/m2, 15 mg/m2 escalation per level) were given on day 1, every 28 days for 4-6 cycles. Filgrastim (F) (5 microg/kg/die) was given in case of grade 4 leukopenia (levels without support) or from day 4 up to leukocyte count >10,000/mm3 after nadir (levels with support). Cohorts of 3 patients were enrolled at each level and further 3 patients were planned if 1 or 2 unacceptable toxic events (UTE) were registered. MTD was determined first without and then with filgrastim. Four levels were studied (90, 90+F, 105+F, 120+F) with 4, 6, 5 and 4 patients enrolled, respectively. UTE (grade 4 neutropenia) were observed in 3 patients at level 1. Thus, 90 mg/m2 was the MTD for epirubicin without filgrastim. MTD of epirubicin with filgrastim was not reached at 120 mg/m2. Hematological toxicity was mild. Grade 3 mucositis was reported in 1 patient. Among the 14 patients with measurable or evaluable disease, 3 objective responses were observed (1 complete and 2 partial) for an overall response rate of 21.4%. The combination of paclitaxel 150 mg/m2 and epirubicin at 120 mg/m2 with filgrastim is a feasible therapy. Grade 4 leukopenia is the dose limiting toxicity using epirubicin at 90 mg/m2 without filgrastim.

Adult↗
PubMed1996

Sterility of filgrastim (G-CSF) in syringes.

OBJECTIVE: To determine if the sterility of filgrastim (G-CSF) is maintained for up to 7 days when aseptically transferred from the vial to tuberculin syringes in a laminar air flow environment. DESIGN: The study was conducted in two phases: a validation and an experimental phase. The method was validated by inoculating samples of sterile filgrastim solution with common bacterial and fungal skin contaminants. Samples were aseptically drawn into syringes in a class 100 horizontal laminar air flow hood and refrigerated. The samples were equally divided and transferred to microbiology culture media at times 0, 24 hours, 48 hours, and 7 days; incubated; and the organisms identified and quantitated. In the experimental phase, samples of filgrastim were aseptically drawn into syringes, separated into three groups, and refrigerated. At 24 hours, 48 hours, and 7 days, the samples were transferred to broth, incubated, and observed for the development of turbidity. SETTING: A class 100 laminar air flow hood in a pediatric hospital pharmacy and a home-infusion pharmacy class 100,000 clean room. MAIN OUTCOME MEASURES: The sterility of filgrastim in syringes was determined by comparing experimental broth culture tubes to a control tube and observing for the development of turbidity. RESULTS: Filgrastim demonstrated the ability to support the growth of intentionally inoculated skin contaminants, both qualitatively and quantitatively. However, when aseptically transferred to syringes and refrigerated, all tested filgrastim samples remained sterile for at least 7 days. CONCLUSIONS: Syringes of filgrastim remain sterile for 7 days when prepared in a class 100 laminar air flow hood, using aseptic technique, and stored under refrigeration. This change in practice can result in significant cost savings.

Drug Contamination↗