Mg Dose Of Pegfilgrastim Research Articles

Reduced dose pegfilgrastim is associated with less bone pain without increased neutropenia: a retrospective study.

Chemotherapy for breast cancer is associated with a high risk of neutropenia. Pegfilgrastim reduces the risk of neutropenic fever but commonly causes bone pain. Evaluate whether a reduced dose of pegfilgrastim (3mg) reduced the frequency of bone pain without compromising efficacy. Records reviewed from breast cancer patients who received at least one 3mg dose of pegfilgrastim, white blood count (WBC), and absolute granulocyte counts (AGC) were collected. Musculoskeletal pain scale was collected at each visit. 265 treatments from 36 women were analyzed. There was no difference in post-treatment AGC between 3 versus 6mg. Leukocytosis (WBC > 20,000 cells/cu mm) was more likely for those treated with 6mg (chi-square 5.265, p = 0.0215). There was higher change in bone pain in patients who received 6mg doses compared to none or 3mg. In this retrospective, non-randomized study, we found the majority of patients received the reduced 3mg dose after intolerance to the 6mg dose. It is unknown if smaller or larger doses than 3mg would achieve similar results or whether 3mg dose would be effective as an initial therapy or for patients receiving different chemotherapy regimens. Pain is observed despite premedication with naproxen and/or loratidine. Reduced dose of pegfilgrastim 3mg was less likely to cause bone pain. The reduced dose was not associated with a significant difference in post-treatment AGC or rate of serious infection.

1574P - Efficacy and safety of RGB-02, a proposed biosimilar pegfilgrastim to prevent chemotherapy-induced neutropenia: Results of a randomized, double-blind, phase III clinical study vs. reference pegfilgrastim in patients with breast cancer receiving docetaxel/doxorubicin

Background: Treatment with recombinant human granulocyte-colony stimulating factor (G-CSF) is accepted standard for prevention of chemotherapy-induced neutropenia. RGB-02, a pegylated G-CSF (pegfilgrastim) developed by Gedeon Richter is a proposed biosimilar to the reference pegfilgrastim product Neulasta®. Here we are presenting the results of a randomized, comparative, double-blind, multicenter study to evaluate efficacy and safety of RGB-02 in breast cancer patients receiving cytotoxic regimen (EudraCT nr: 2013-003166-14). Methods: 239 women presenting with breast cancer were randomized to RGB-02 (n = 121) and to the reference pegfilgrastim, Neulasta® (n = 118). All patients received up to 6 cycles of docetaxel/doxorubicin and a once-per-cycle injection of a fixed 6 mg dose of pegfilgrastim. Primary endpoint was the duration of severe neutropenia (ANC < 0.5 x109/L) in Cycle 1 (2-sided CI interval 95%). Secondary endpoints included incidence and duration of severe neutropenia, incidence of febrile neutropenia, time to ANC recovery, depth of ANC nadir, and safety outcomes. Results: The mean duration of severe neutropenia in Cycle 1 was 1.7 (RGB-02) and 1.6 days (reference), with a difference (LS Mean) of 0.1 days (95% CI -0.2, 0.4). Therapeutic equivalence could be established as the CI for the difference in LS Mean lay entirely within the pre-defined range of ± 1 day. The incidence of severe neutropenia decreased from cycle 1 to 2 in both groups with no statistical significant differences, for RGB-02 from 84.6% (99 patients) to 54.1% (60 patients) and from 77.0% (87 patients) to 43.7% (45 patients) in the comparator group. Both groups were similar regarding mean time to ANC recovery with 3.4 ± 1.84 days (RGB-02) and 3.7 ± 1.88 days (reference) during Cycle 1. Safety profiles were comparable between groups. Conclusions: Therapeutic equivalence and similar safety profiles between RGB-02 and Neulasta® as once-per-cycle administration could be demonstrated. RGB-02 can provide a biosimilar alternative for the prevention of neutropenia. Clinical trial identification: EudraCT nr: 2013-003166-14 Legal entity responsible for the study: Gedeon Richter Plc. Funding: Gedeon Richter Plc. Disclosure: K. Horvat-Karajz, A. Illes: Employee of Gedeon Richter Plc. All other authors have declared no conflicts of interest.

To analyze efficacy and safety of pegfilgrastim versus filgrastim in patients with breast cancer

e20587 Background: We evaluated the safety and 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. Methods: Patients with carcinoma of breast, less than 65 yrs with ECOG performance status 0 or 1 treated at our institution 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 adjuvant or neoadjuvant chemotherapy with doxorubicin, cyclophosphamide and docetaxel (60 mg/m, 600 mg/m2 and 75 mg/m2, respectively)q3 wk. Duration of grade 4 neutropenia (DSN), incidence of febrile neutropenia (FN), grade 4 neutropenia (SN), IV anti-infective use (IV), hospitalization and adverse events like bony pain (BP), anemia &amp; thrombocytopenias were assessed as safety endpoints. Results: 71 patients were analyzed from Aug 2007 to Dec 2008. The median age in pegfilgrastim group is 58 years and filgrastim is 57 years respectively. Results are shown ( Table ). The mean duration of grade 4 neutropenia (DSN) in cycle 1 was 2.0 and 1.7 days for the pegfilgrastim and filgrastim groups, respectively. Results for all efficacy end points in cycles 2–6 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 (10.7% versus 18.6%, respectively). Conclusions: A single fixed dose of pegfilgrastim administered once per cycle of chemotherapy was comparable to multiple daily injections of filgrastim. [Table: see text] No significant financial relationships to disclose.

Pegfilgrastim compared with filgrastim after high‐dose melphalan and autologous hematopoietic peripheral blood stem cell transplantation in multiple myeloma patients

We undertook a comparative study of Pegfilgrastim vs. Filgrastim after high-dose melphalan and autologous peripheral blood stem cell transplantation (APBSCT) in multiple myeloma (MM) patients. Thirty-seven consecutive patients were randomly assigned to receive a single 6 mg dose of Pegfilgrastim on day 1 post-transplant (n = 18 patients) vs. daily subcutaneous injections of Filgrastim 5 microg/kg (n = 19 patients) starting on day 5 post-transplant. The median duration of grade 4 neutropenia in the Pegfilgrastim and Filgrastim groups was 5 and 6 d, respectively (P = ns). The results for the two groups were also not significantly different for time to neutrophil and platelet recovery, but incidence of febrile neutropenia (61.1% vs. 100%, P = 0.003) and duration of febrile neutropenia (1.5 d vs. 4 d, P = 0.005), were lower in the Pegfilgrastim arm. After initial haematopoietic reconstitution, we observed significantly higher value of leukocytes x 10(9) L on day 15 (6.0 vs. 2.7, P = 0.004), in the Pegfilgrastim group compared with the Filgrastim group. This study shows that a single injection Pegfilgrastim can be used with safety and efficacy similar to those provided by daily injections of Filgrastim and it is associated with a decrease incidence of infectious events after APBSCT in MM patients.

Efficacy of single dose pegfilgrastim in enhancing the mobilization of CD34+ peripheral blood stem cells in aggressive lymphoma patients treated with cisplatin-aracytin-containing regimens

Systematic data on the ability of pegfilgrastim to mobilize stem cells after chemotherapy are scarce. We evaluated the efficacy of a single 6 mg dose of pegfilgrastim for mobilizing peripheral blood stem cells (PBSC) in aggressive lymphoma patients. Between July 2004 and October 2005, 17 aggressive non-Hodgkin's lymphoma and 11 poor-risk Hodgkin's lymphoma were treated with cycles containing cisplatin-aracytin. At the end of chemotherapy, the patients received 6 mg of pegfilgrastim. Duration of grade 4 neutropenia, adverse events, time to neutrophil recovery, peak and harvest of CD34+ cells were recorded. Twenty-seven out of 28 patients harvested a median of 17.3 x 10(6)/CD34+ cells (range 2.5-28.9) after a median of 9 days (range 8-12 days), with a single apheresis procedure in 25 cases. All patients had grade 3-4 neutropenia, median duration 3 days. The only adverse event was mild bone pain. To date, 13 patients have been autografted with a median of 15.4 x 10(6) CD34+ pegfilgrastim-mobilized cells per kg (range 2.5-28.9) with rapid and sustained engraftment. Mobilization, harvesting and autografting of pegfilgrastim-mobilized PBC can be successfully achieved in pretreated patients with aggressive lymphoma.

Good Efficacy of Single Dose PEG-Filgrastim in Enhancing the Mobilization of CD34+ Peripheral Blood Stem Cells (PBSC) in Aggressive Lymphoma Patients Treated with Cisplatin-Containing Regimens.

Background. Pegfilgrastim is a polyethylene glycol (PEG)-conjugated form of G-CSF in which filgrastim is bound covalently to a 20kDa PEG molecule; this formulation increases serum half-life of G-CSF due to decreased renal elimination. Following the subcutaneous injection of a 6 mg single dose of pegfilgrastim, serum levels of G-CSF are maintained over a period of 2 weeks. In patients with lymphoma, pegfilgrastim is as effective as filgrastim in shortening the time of neutropenia after cytotoxic chemotherapy; however, the ability of pegfilgrastim to mobilize stem cells after chemotherapy is poorly understood and the optimal mobilization strategy remains controversial.Aims. We evaluate the efficacy of a single fixed 6 mg dose of pegfilgrastim after salvage therapy with cisplatin-containing chemotherapy regimens in mobilizing peripheral blood stem cells in aggressive lymphoma patients. Moreover the possibility of a sufficient collection of CD34+ PBSC (cell dose > 2,5 x106/Kg) in a single procedure was tested.Methods. Between July 2004 and July 2005 twenty two pretreated patients with aggressive lymphoma (8 Hodgkin's lymphoma, 11 diffuse large B cell lymphoma, 3 anaplastic lymphoma) received salvage chemotherapy with cisplatin-based regimens: (R)-DHAP, dexametasone, cisplatin, cytarabine, or (R)-IPAD idarubicin, dexametasone, cisplatin, cytarabine, with or without Rituximab. A 6 mg single dose of pegfilgrastim was given from day +1 or +2 after chemotherapy completion. Duration of grade 4 neutropenia, adverse events, time to neutrophil and CD34+ cell recovery were recorded. Stem cell collection was started when the absolute number of CD34+ was not less than 20/μL. Leukapheresis was daily performed until the minimum target cell dose of 2.5 x 10 6 CD34+ cells /kg was reached.Results. Following the administration of either (R)-DHAP or (R)-IPAD regimens, 21/ 22 pts (95%) were able to harvest a median of 14,2 x 10 6/Kg CD34+ cell (range 2,4– 45,8), after a median of 9 days from stimulation (range 8–12). A single apheresis procedure was sufficient to obtain a median of 14,8 x 10 6/kg CD34+ cell (range 5,2–45,8) in 18/21 pts (86%) Grade 4 neutropenia was present in all pts with a median duration of 3 days (range 1–7). Pegfilgrastim determined mild bone pain as only adverse event. Seven patients underwent autologous bone marrow transplantation and all of them showed a rapid and sustained engraftment after high-dose chemotherapy.Conclusions. In aggressive lymphoma patients a single dose of pegfilgrastim following chemotherapy completion was safe and highly effective in enhancing the mobilization of CD34+ PBSC. Stem cell collection was performed in a single procedure in most of patients (86%) obtaining a stem cell harvest of a median of 14,8 x 106/Kg CD34+ cells. In 7 autologous bone marrow transplanted patients these results determined early engraftment and sustained hematological reconstitution.

Pegfilgrastrim Compared with Filgrastim after Autologous Hematopoietic Peripheral Blood Stem Cell Transplantation.

In order to assess the effect of Pegfilgrastim on the duration of neutropenia and clinical outcome of patients after autologous peripheral blood stem cell transplantation (PBSCT), we compared 20 consecutive patients with lymphoma or multiple myeloma receiving a single 6 mg dose of Pegfilgrastim on day 1 posttransplant to a historical control group of 60 patients receiving daily Filgrastim 5 μg/kg starting on day 1 posttransplant. There were 54 M and 26 F, 30 patients with lymphoma and 50 with myeloma, 26 in CR and 54 not in CR. Mean age was 55±10 yrs and 25 had already received a previous autologous transplant. The two groups were matched for disease and disease status, transplant number, age and sex. Cell dose infused tended to be higher in the Pegfilgrastim group (7.16±3.82 vs 10.03±6.25 x106 CD34+ cells/kg, p=0.0575). There were no differences (p>0.05) in time to 0.5 (8 vs 9 days) or 1 (9 vs 9 days) x109/L neutrophils; to 1 % reticulocytes (13 vs 15 days) or 9 (12 vs 14 days) or 10 (30 vs 25 days) g/dL Hb; to 20 (9 vs 9 days) or 100 (20 vs 31 days) x 109/L platelets. The number of days with fever (2.7±2.3 vs 2.3±2.4 days), incidence of infections (all infections; bacteremia; bacterial, fungal or viral infections; FUO), duration of antibiotic therapy (8.7±5.9 vs 8.4±5.9 days), RBC (1.1±1.6 vs 0.9±1.6) and platelet (1.0±1.7 vs 1.2±1.8) transfusions, and time to hospital discharge (14.5±5.3 vs 15.4±5.8 days) were similar in the Pegfilgrastim compared to the Filgrastim group. However, after initial hematopoietic recovery, several differences between the groups became apparent, with the group always showing higher counts compared to the Filgrastim group (p values <0.05 to <0.001). Neutrophils remained significantly higher in the Pegfilgrastim group between days 14–30, lymphocytes between days 56–90, monocytes between days 21–24, reticulocytes between days 17–42 and platelets between days 35–90, respectively. These differences had no impact on clinical outcome after day 30 due to the low incidence of infectious events after engraftment. We conclude that Pegfilgrastim administrated on day 1 posttransplant facilitates early hematopoietic reconstitution comparable to daily Filgrastim. However, despite a trend towards fewer CD34+ cells transplanted, the Pegfilgrastim group enjoyed higher trilineage cell counts for some time after initial engraftment. This should be further tested in prospective randomized trials.

Peg-Filgrastim after High Dose Chemotherapy and Autologous Peripheral Blood Stem Cell Transplantation for Hematological Malignancies: A Matched-Pair Analysis.

G-CSF is used to enhance neutrophil recovery after autologous peripheral blood stem cell transplantation (aPBSCT), even if the optimal timing and dose of G-CSF has not been established. Recently Peg-Filgrastim has been approved for clinical use. The clearance of Peg-Filgrastim is neutrophil-mediated with a sustained duration of action with prolonged serum concentration during neutropenia. In order to verify the efficacy and feasibility of use of Peg-Filgrastim, we administered to 10 patients (A Group, 3F, 7M, median age 46y) submitted to aPBSCT for haematological malignancies (6 NHL, 3 MM, 1 HD) a single 6 mg dose of Peg-Filgrastim subcutaneously on day +1 and we compared the engraftment of these patients to data of a group of 30 patients (B group 9F, 21M, median age 46y, 18 NHL, 6 MM, 2 POEMS syndrome, 1 Plasmacell leukemia, 3 HD) submitted to aPBSCT not receiving G-CSF. Patients were matched for sex, age, disease, disease status at transplant, conditioning regimen, transplant procedure and they received comparable CD34+ cell dose. We evaluated haematological engraftment, and other clinical outcomes, all results are expressed as a median value in the table. Peg-Filgrastim was well tolerated in all but 1 patient reporting bone pain. Neutrophil engrafment was significantly faster (72 hours) in the Peg-Filgrastim group: days +10 and +12 (500 and 1000 cells/μL) vs days +13 and +15.5 of control group; faster neutrophil engraftment was also clear analyzing number of days with absolute neutrophil count (ANC) <100 cells/μL: 4 days vs 6 days. We did not observe statistically significant differences in erythroid and platelet recovery, time to discharge, bloodstream infections, days of fever, days of non prophylactic antibiotic therapy. Otherwise, transfusional requirements were significantly higher in patients receiving Peg-Filgrastim; these results are consistent with observed delay, although not statistically significant, in platelet and erythroid recovery. In conclusion, Peg-Filgrastim is safe, efficacious and improves neutrophil recovery, after aPBSCT; our data suggest a possible detrimental effect on erythroid and platelets recovery but larger trials are needed to confirm it and, particularly, to assess whole clinical benefits of such approach to justify its economical impact.ResultsA GroupB GroupStatistical analysisDays to ANC > 500/μL10 (7–11)13 (7–18)p<0.0001Days to ANC > 1000/μL12 (7–15)15.5 (10–38)p<0.0001Days of ANC < 100/μL4 (3–5)6 (3–12)p=0.0078Days to Plts > 20 x 10³/μL11 (8–24)12 (9–18)p=0.4Days to Plts > 50 x 10³/μL24 (12–39)14 (10–60)p=0.39Days to Plts > 100 x 10³/μL40 (14–120)18 (12–210)p=0.06Days to Reticulocytes >1%15 (11–16)13.5 (10–30)p=0.59Days to Hgb >10 g/dl33 (10–84)21 (10–210)p=0.48Days of fever5 (2–10)5 (2–13)p=0.92Days of antibiotic therapy7 (5–20)9.5 (5–18)p=0.72Bloodstream infections4/106/30p=0.2Number of pRBCu1 (0–2)0 (0–2)p=0.02Number of SDu1.5 (1–3)1 (0–2)p=0.022Days of hospitalization25 (19–30)23 (20–34)p=0.89

Pegylated Recombinant Human Granulocyte Colony Stimulating Factor (pegfilgrastim) Reduces Hematological Toxicity in Dose-Adjusted (DA) R-EPOCH in the treatment of Diffuse Large B Cell Lymphoma.

Hematological toxicity is a significant dose limiting side effect in the aggressive treatment of Diffuse Large B Cell Lymphoma (DLBCL). In the current study, pegfilgrastim was given to patients following each cycle of DA R-EPOCH. ANC and platelet nadirs were then compared to a previous report utilizing filgrastim. Pegfilgrastim is a covalent conjugate form of filgrastim, whereby a molecule is covalently bonded to the N terminal of filgastrim, allowing the molecule to be cleared slower than filgastrim. The prolonged effect on the promotion of granulocyte proliferation allows for pegfilgrastim to be given once every 2 weeks in comparison to filgrastim which is injected daily. In this study, records of 5 patients treated with DA R-EPOCH for DLBCL were examined. There were a total of 20 cycles with 15 cycles qualifying for analysis in regards to hematological toxicity. To qualify each cycle met the following criteria: i) treatment with R-EPOCH at starting dose or dose-escalation; ii) pegfilgrastim was administered 24 to 48 hours after completion of chemotherapy at the standard dose of 6mg sc; iii) follow-up of at least two weeks following each cycle; iv) CBC monitored at least once weekly. Of the cycles excluded, 3 cycle did not have at least 2 weeks of follow-up, 1 cycle was followed by filgrastim and 1 cycle was treated with R-CHO. Nadir was defined as lowest value obtained from initiation of one cycle to initiation of next cycle or to two weeks from last day of all chemotherapy. Hematological toxicities were graded according to WHO criteria. Grade 4 neutropenia (ANC less than 0.5 x 109/L) occurred in 13% (2/15) of cycles. There was no Grade 3 neutropenia (ANC 0.5 – 1.0 x 109/L). Range of ANC nadir was 0.02 – 4.4 x 109/L with mean of 2.4 x 109/L. There was no Grade 3 thrombocytopenia (Platelet 25 – 50 25 x 109/L) nor Grade 4 thrombocytopenia (Platelet < 25 x 109/L). Range of platelet nadir was 53 – 230 x 109/L with mean of 130. Examining treatment records, 13 cycles of 20 were candidates for dose escalation. Each cycle was included if it followed a cycle of R-EPOCH and the patient had received pegfilgrastim for neutropenic support. Excluded cycles included 5 cycles at starting doses, 1 cycle in which filgrastim was administered prior, and 1 cycle in which the R-CHO was given prior. Following the criteria for allowable DA EPOCH according to the paradigm published in Blood Apr 15, 2002, Vo 99, No 8 pp 2685– 2693, dose escalation was allowed for ANC of at least 0.5 x 109/L and platelets of at least 25 x 109/L. 11 of 13 (85%) cycles in this study were eligible for dose escalation based on the above mentioned paradigm. In the previous mentioned publication filgrastim was given after completion of each cycle of EPOCH with 49% of cycles complicated by Grade 4 neutropenia and 7% complicated by Grade 4 thrombocytopenia. 58% of the cycles were dose escalated in the previous study. In conclusion this study indicates that pegfilgrastim results in less hematological toxcity in DA R-EPOCH. This allows for DA in a higher percentage of treatment cycles. In addition, examination of the cost reveals the average whole sale price of a single 6 mg dose of pegfilgrastim is $3127, while the average whole sale price of a daily dose of 480 mcg of filgrastim for 10 days is $3500.

Is pegfilgrastim appropriate for the treatment of established febrile neutropenia?

Objective. To report a case where both pegfilgrastim and filgrastim were considered in the treatment of febrile neutropenia in a hospitalized patient and assess the most cost-effective option. Case summary. A 77-year-old white female was diagnosed with squamous cell carcinoma of the anus and adjuvant chemotherapy was ordered. She subsequently developed Grade 4 neutropenia, a wound infection and her Eastern Cooperative Oncology Group (ECOG) performance status declined to 4. Antibiotics were started and growth factor therapy was considered as part of her treatment. Filgrastim 480 g subcutaneously every day was chosen and her absolute neutrophil count (ANC) recovered after seven days of therapy. Discussion. This case illustrates the potential cost benefits of using filgrastim over pegfilgrastim in hospitalized patients. The choice of filgrastim in our patient resulted in only seven days of filgrastim therapy at a cost of $2205.70. A 6 mg dose of pegfilgrastim is priced similarly to 10 days of filgrastim 480 g, therefore a cost savings of $744.01 was realized in our patient. Conclusions. Filgrastim is the most appropriate growth factor for the treatment of established high-risk febrile neutropenia given that the ANC can be monitored on a daily basis and therapy can be discontinued upon recovery.

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

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 (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. 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. 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.