Filgrastim Arm Research Articles

A pilot study on intermittent every other days of 5-dose Filgrastim compared with single Pegfilgrastim in breast Cancer patients receiving adjuvant Docetaxel, doxorubicin, and cyclophosphamide (TAC) chemotherapy.

Aim To compare the efficacy and safety of intermittent every other days 5-dose filgrastim with single pegfilgrastim in patients with breast cancer receiving adjuvant docetaxel, doxorubicin, and cyclophosphamide (TAC) chemotherapy. Methods In this pilot study, Korean patients who had undergone complete resection for breast cancer and scheduled for adjuvant TAC chemotherapy were enrolled. Patients were randomized to receive either intermittent 5 doses of filgrastim (5 mcg/kg/day) or once-a-cycle pegfilgrastim (6mg) as primary prophylaxis during the first three cycles of the TAC chemotherapy. Absolute neutrophil count (ANC) was analyzed as well. Results A total of 22 patients were randomly and equally divided into filgrastim or pegfilgrastim arms. Febrile neutropenia (FN) occurred in 1 patient in the pegfilgrastim arm (1 of 33cycles) and none in the filgrastim arm. G3 neutropenia occurred in 1 patient (1 of 33cycles) in the filgrastim arm and 2 patients (4 of 33cycles) in the pegfilgrastim arm (P = 0.476). G4 neutropenia occurred in 11 patients (28 of 33cycles) in the filgrastim arm and 9 patients (18 of 33cycles) in the pegfilgrastim arm (P = 0.476). Except for on day 9 in cycle 3, there was no significant difference between the two groups in terms of ANC. Conclusion We observed no significant differences between the two methods of prophylaxis in terms of FN and G3/4 neutropenia incidence in patients receiving adjuvant TAC chemotherapy. Intermittent every other days 5-dose filgrastim may be available alternative to pegfilgrastim.

Results of a Prospective Randomized, Open-Label, Noninferiority Study of Tbo-Filgrastim (Granix) versus Filgrastim (Neupogen) in Combination with Plerixafor for Autologous Stem Cell Mobilization in Patients with Multiple Myeloma and Non-Hodgkin Lymphoma

Autologous hematopoietic stem cell transplantation (auto-HSCT) improves survival in patients with multiple myeloma (MM) and non-Hodgkin lymphoma (NHL). Traditionally, filgrastim (Neupogen; recombinant G-CSF) has been used in as a single agent or in combination with plerixafor for stem cell mobilization for auto-HSCT. In Europe, a biosimilar recombinant G-CSF (Tevagrastim) has been approved for various indications similar to those of reference filgrastim, including stem cell mobilization for auto-HSCT; however, in the United States, tbo-filgrastim (Granix) is registered under the original biological application and is not approved for stem cell mobilization. In retrospective studies, stem cell mobilization with tbo-filgrastim has shown similar efficacy and toxicity as filgrastim, but no prospective studies have been published to date. We have conducted the first prospective randomized trial comparing the safety and efficacy of tbo-filgrastim in combination with plerixafor with that of filgrastim in combination with plerixafor for stem cell mobilization in patients with MM and NHL. This is a phase 2 prospective randomized (1:1) open-label single-institution noninferiority study of tbo-filgrastim and filgrastim with plerixafor in patients with MM or NHL undergoing auto-HSCT. Here 10 µg/kg/day of tbo-filgrastim/filgrastim was administered s.c. for 5 days (days 1 to 5). On day 4 at approximately 1800 hours, 0.24 mg/kg of plerixafor was administered s.c. Apheresis was performed on day 5 with a target cumulative collection goal of at least 5.0 × 106 CD34+ cells/kg. The primary objective was to compare day 5 CD34+ cells/kg collected. Secondary objectives included other mobilization endpoints, safety, engraftment outcomes, and hospital readmission rate. A total of 97 evaluable patients were enrolled (tbo-filgrastim, n = 46; filgrastim, n = 51). Tbo-filgrastim was not inferior to filgrastim in terms of day 5 CD34+ cell collection (mean, 11.6 ± 6.7 CD34+ cells/kg versus 10.0 ± 6.8 CD34+ cells/kg. Multivariate analysis revealed a trend toward increased mobilization in the tbo-filgrastim arm, but this was not statistically significant. The tbo-filgrastim and filgrastim arms were similar in all secondary endpoints. Tbo-filgrastim is not inferior in efficacy and has similar safety compared to reference filgrastim when used for stem cell mobilization in patients with MM and NHL. Granix can be safely used instead of Neupogen for stem cell collection in patients undergoing auto-HSCT for MM or NHL.The study is registered at https://clinicaltrials.gov/ct2/show/NCT02098109.

A Randomized Trial of Tbo-Filgrastim Versus Filgrastim for Autologous Stem Cell Mobilization in Patients with Multiple Myeloma or Non-Hodgkin Lymphoma

Background: Tbo-filgrastim, biosimilar to filgrastim, was approved by the FDA in 2012 as a new drug due to the lack of a biosimilar approval pathway at time of submission. Like filgrastim, tbo-filgrastim is currently indicated for the treatment of neutropenia following chemotherapy; however, filgrastim is also indicated for mobilization of hematopoietic progenitor cells for autologous stem cell transplantation (ASCT) while tbo-filgrastim is not. In Europe, tbo-filgrastim carries all the indications that filgrastim does, however, no prospective studies have been completed comparing tbo-filgrastim and filgrastim for ASCT mobilization. Therefore, we conducted a single-institution randomized phase 2 trial.Objectives: 1) To compare peripheral blood (PB) CD34+ counts, CD34+ apheresis yield, toxicity, and post-ASCT engraftment in patients mobilized with tbo-filgrastim versus filgrastim.Methods: Participants were at least 18-years-old and had multiple myeloma (MM) or non-Hodgkin's Lymphoma (NHL). Those with impaired hematologic function and those who had undergone a previous ASCT mobilization were excluded. Participants were randomized (1:1) to tbo-filgrastim or filgrastim. Tbo-filgrastim/filgrastim (10mcg/kg) was administered daily for 5 days. On the evening of Day 4, plerixafor (0.24 mg/kg) was administered; apheresis (20L) was performed on Day 5. If a participant failed to achieve the target collection goal (5.0x106 cells/kg) on Day 5, he/she continued to receive daily tbo-filgrastim/filgrastim, plerixafor, and apheresis for a maximum of 3 additional days. Participants who subsequently underwent ASCT were followed for platelet and neutrophil engraftment.Statistics: PB CD34+ counts and CD34+ apheresis yields were compared using Mann-Whitney U, engraftment using log-rank.Results: At the time of abstract submission, corresponding with interim analysis 1, 51 participants were enrolled and 49 were evaluable for analysis; 24 received tbo-filgrastim, 25 filgrastim. The median age was 60 years (range 40-77); 63% (31) were male; 86% (42) had MM, 14% (7) NHL. Both treatment arms were similar in demographics and baseline blood counts.Post-mobilization PB CD34+ counts were similar between both arms. The median PB CD34+ count on day 4 (pre-plerixafor) was 20/mcL for tbo-filgrastim and 22/mcL for filgrastim (p=0.647); on Day 5 pre-apheresis it was for 94/mcL for tbo-filgrastim and 92/mcL for filgrastim (p=0.726). CD34+ apheresis yield was also similar; the median Day 5 CD34+/kg apheresis yield was 10.9x106 for tbo-filgrastim and 12.0x106 for filgrastim (p=0.889).Seventy-five percent of the tbo-filgrastim arm reached the collection goal after one day of apheresis, 76% of the filgrastim arm did (p=0.935). Ninety-six percent of patients on the tbo-filgrastim arm reached the goal in 4 or less days of apheresis, 92% of the filgrastim arm did (p=0.576). All patients treated collected > 2.0x106 cells/kg, the minimum required for ASCT, following < 2 days of apheresis. Both treatment arms had similar toxicity.Thirty-nine patients have subsequently undergone ASCT and evaluable for engraftment, 18 on the tbo-filgrastim arm and 21 on the filgrastim arm. The median interval of neutrophil engraftment for tbo-filgrastim was 12 days compared to 11 for filgrastim (p=0.178); the median interval of platelet engraftment was 17 days for both arms (p=0.238).Mobilization, collection, toxicity, and engraftment data are summarized in Table 1.Conclusion: Tbo-filgrastim appears to be similar to filgrastim for ASCT mobilization in patients with MM or NHL. Planned study enrollment is 100 evaluable patients; updated study results will be presented.Table 1Tbo-FilgrastimFilgrastimPB CD34+/mcl on Day 41(median & range)20 (4-68)22 (1-115)PB CD34+/mcl on Day 5 (median & range)94 (18-187)92 (11-314)CD34+/kg x106 yield on Day 5 (median & range)10.9 (1.4-21.2)12.0 (1.3-28.4)CD34+/kg yield >2.0 on Day 596%92%CD34+/kg yield >5.0 on Day 575%76%CD34+/kg yield >2.0 in < 4 days100%100%CD34+/kg Yield >5.0 in < 4 days96%92%Post-ASCT EngraftmentDays to Neutrophil Engraftment (median & range)12 (10-20)11 (10-13)Days to Platelet Engraftment (median & range)17 (13-23)17 (13-22)1-Prior to plerixafor dose DisclosuresVij:Celgene, Onyx, Takeda, Novartis, BMS, Sanofi, Janssen, Merck: Consultancy; Takeda, Onyx: Research Funding. Abboud:Teva Phamaceutical: Research Funding.

Cost Effectiveness of Pegfilgrastim Versus Filgrastim After High-Dose Chemotherapy and Autologous Stem Cell Transplantation in Patients with Lymphoma and Myeloma

Use of the recombinant human granulocyte colony-stimulating factor (rhG-CSF) filgrastim accelerates neutrophil recovery following myelosuppressive chemotherapy. Since filgrastim requires multiple daily administrations, forms of rhG-CSF with a longer half life, including pegfilgrastim, have been developed. Pegfilgrastim is safe and effective in supporting neutrophil recovery and reducing febrile neutropenia after conventional chemotherapy. Pegfilgrastim has also been successfully used to support patients undergoing peripheral blood stem cell (PBSC) transplantation for haematological malignancies. To our knowledge, no cost-effectiveness analysis (CEA) of pegfilgrastim in this setting has been published yet. We undertook a CEA to compare a single injection of pegfilgrastim versus repeated administrations of filgrastim in patients who had undergone PBSC transplantation for lymphoma or myeloma. The CEA was set in France and covered a period of 100±10days from transplant. The CEA was designed as part of an open-label, multicentre, randomized phase II trial. Costs were assessed from the hospital's point of view and are expressed in 2009euros. Costs computation focused on inpatient, outpatient, and home care. Costs in the two arms of the study were compared using the Mann-Whitney test. When differences were statistically significant, multiple regression analyses were performed in order to identify cost drivers. Incremental cost-effectiveness ratios (ICER) were calculated for the major endpoints of the trial; i.e., duration of febrile neutropenia (absolute neutrophil count [ANC] <0.5×10(9)/L and temperature ≥38°C), duration of neutropenia (ANC <1.0×10(9)/L and ANC <0.5×10(9)/L), duration of thrombopenia (platelets <50×10(9)/L and <20×10(9)/L), and days with a temperature ≥38°C). Uncertainty around the ICER was captured by a probabilistic analysis using a non-parametric bootstrap method. 151 patients were enrolled at ten French centres from October 2008 to September 2009. The mean total cost in the pegfilgrastim arm of the study (n=74) was <euro>25,024 (SD 9,945). That in the filgrastim arm (n=76) was <euro>28,700 (SD 20,597). Pegfilgrastim strictly dominated filgrastim for days of febrile neutropenia avoided, days of neutropenia (ANC <1.0×10(9)/L) avoided, days of thrombopenia (platelets <20×10(9)/L) avoided, and days with temperature ≥38°C) avoided. Pegfilgrastim was less costly and less effective than filgrastim for the number of days with ANC <0.5×10(9)/L avoided and the number of days with platelets <50.0×10(9)/L avoided. Taking uncertainty into account, the probabilities that pegfilgrastim strictly dominated filgrastim were 67% for febrile neutropenia, 86% for neutropenia (ANC <1.0×10(9)/L), 59% for thrombopenia (platelets <20×10(9)/L), 86% for temperature ≥38°C, 32% for neutropenia (ANC <0.5×10(9)/L), and 43% for thrombopenia (platelets <50×10(9)/L). Conversely, the probability that filgrastim strictly dominated pegfilgrastim for neutropenia (ANC <0.5×10(9)/L) is 5%. This study found no evidence that the use of pegfilgrastim is associated with greater cost in lymphoma and myeloma patients after high-dose chemotherapy and PBSC transplantation.

P1-14-01: Randomized Phase II Trial of Weekly vs. q 2-Weekly vs. q 3-Weekly Nanoparticle Albumin-Bound Paclitaxel with Bevacizumab as First-Line Therapy for Metastatic Breast Cancer.

Abstract Background: Nanoparticle albumin-bound paclitaxel (nab-P) 260 mg/m2 is superior to paclitaxel 175 mg/m2 (P) every 3 weeks (Gradishar et al. JCO 2005) in metastatic breast cancer (MBC), and weekly uninterrupted P is more effective than q3wk P in MBC (Seidman et al. JCO 2008). Bevacizumab (bev) nearly doubles response rate and time to progression (TTP) when added to P as 1st line therapy for MBC (Miller et al. NEJM 2007). Methods: This open-label, phase II study randomized patients (pts) to nab-P at 260 mg/m2 q3wk (arm A) vs. 260 mg/m2 q 2wk with filgrastim (arm B) vs. 130 mg/m2 weekly uninterrupted (arm C), all with bev (15 mg/kg q 3 weeks arm A, 10 mg/kg q 2 weeks arms B and C). Patients were required to have measurable, HER2 negative MBC and no prior chemotherapy for MBC. The primary endpoints were response rate and toxicity. Results: Of 212 pts randomized, 208 (75 arm A, 54 arm B, 79 arm C) were treated, with balanced demographics and baseline characteristics. The median age was 57 (range 29–85), 82% were postmenopausal and 89% had visceral disease (64% lung, 50% liver). ECOG PS 0:60%, 1:35%, 2:5%. 62% had prior neo-adjuvant or adjuvant chemotherapy for early stage disease: anthracycline: 54%, taxane: 38%. No significant differences in confirmed complete and partial response rates were noted (A: 40%, B: 44%, C: 46%). Median TTP was longer in Arm C (9.0 months) versus both arms B (6.3 months) and A (8.0 months), overall p=0.065. There were no differences in overall survival (Arm A: 21.3 months, Arm B: 19 months, Arm C: 25.3 months). As per protocol-specified stopping rule, arm B was closed early due to an unacceptable safety profile with significantly more grade ≥ 2 fatigue (B:57%, A: 39%, C:39%, p=0.048) and bone pain (B:19%, A:10%, C:4%, p=0.024). Sensory neuropathy was common; grades 2/3/4: Arm A: 29%/32%/1%, Arm B: 15%/50%/2%, Arm C: 27%/43%/1%). Sensory neuropathy was commonly readily reversible with dose delay and reduction. Febrile neutropenia occurred in &amp;lt;2% of pts in all arms. Arm C patients experienced significantly less arthralgia compared with arms A and B, but dose delays were frequent (86% of pts) on this planned uninterrupted weekly schedule. Bevacizumab-related events were consistent with prior phase III trials of taxane/bev; there were no new safety signals. Conclusions: Significant and similar antitumor activity was observed in all arms. Weekly nab-P with bev (arm C) resulted in longer TTP. Weekly nab-P with bev (arm C) appears to have the highest therapeutic index, however sensory neuropathy is limiting, suggesting that a 3 week on/1 week off schedule could be preferable and should be studied comparatively. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-14-01.

Comparison of daily filgrastim and pegfilgrastim to prevent febrile neutropenia in Asian lymphoma patients

Febrile neutropenia (FN) is a highly prevalent complication of chemotherapy, particularly in patients with non-Hodgkin's lymphoma. This study aimed to compare the efficacy of filgrastim and pegfilgrastim in Asian lymphoma patients by evaluating the incidence of FN and associated complications. This was a single-center, retrospective cohort study in Asian lymphoma patients who received chemotherapy with primary prophylactic granulocyte colony-stimulating factors support between January 2008 and August 2009. Data were analyzed using an intent-to-treat approach, which aimed to reflect actual prescribing practices. A total of 204 Asian lymphoma patients were included in this study, with 81 patients in the filgrastim arm and 123 patients in the pegfilgrastim arm. Overall, the incidence of breakthrough FN was similar between the two groups of patients (13.6%: filgrastim arm vs 16.3%: pegfilgrastim arm; P=0.69). Neutropenic complications such as chemotherapy treatment delay and chemotherapy dose reduction were similar between the two arms. In Asian patients, pegfilgrastim prophylaxis did not show a therapeutic advantage for preventing neutropenic outcomes compared with filgrastim prophylaxis.

Reported Bone Pain in Patients with Breast Cancer Receiving Taxane-Based Chemotherapy in Clinical Trials of Pegfilgrastim.

Abstract Background: The most commonly reported adverse event associated with administration of granulocyte colony-stimulating factors (G-CSFs) is mild to moderate bone pain. It has been suggested (but not uniformly accepted) that bone pain associated with pegfilgrastim treatment occurs at a higher frequency, is more severe and less predictable than bone pain associated with filgrastim treatment. This retrospective analysis examined bone pain in patients with breast cancer receiving chemotherapy in pegfilgrastim clinical trials.Methods: Data analyzed are from 3 sponsor-supported trials of once per chemotherapy cycle pegfilgrastim (6 mg fixed dose or 30, 60, or 100 mcg/kg) or daily filgrastim (5 mcg/kg) administered 24 hours after taxane-containing chemotherapy in patients with breast cancer (Holmes et al Ann Oncol 2002;13:903; Holmes et al JCO 2002;20:727; Green et al Ann Oncol 2003;14:29). The adverse events reported in the 3 studies were recoded using MedDRA dictionary and the preferred terms considered bone pain were determined prior to the analysis. Incidence of any grade and grade 3/4 bone pain was determined by treatment (pegfilgrastim or filgrastim) and cycle.Results: Patients receiving pegfilgrastim (n = 356) or filgrastim (n = 252) were included in the analysis. In the 3 breast cancer studies included in this analysis, the proportions of patients who had metastatic disease at study entry ranged from 19% to 48%. The overall incidence of any grade bone pain was 65.7% and 67.9% in the pegfilgrastim and filgrastim arms, respectively (Table). In both treatment arms, bone pain incidence was highest in the first cycle of chemotherapy and decreased in subsequent cycles. Grade 3/4 bone pain was infrequently reported in these studies. PegfilgrastimFilgrastim n = 356n = 252Female, n (%)354 (99.4)250 (99.2)White, n (%)289 (81.2)213 (84.5)Age, mean years (min, max)51 (23, 81)52 (27, 83)Bone pain (any grade), % (95% CI) All cycles65.7 (60.5, 70.7)67.9 (61.7, 73.6)Cycle 146.1 (40.8, 51.4)52.8 (46.4, 59.1)Cycle 230.1 (25.3, 35.3)30.4 (24.7, 36.5)Cycle 325.7 (21.1, 30.7)29.5 (23.9, 35.7)Cycle 423.4 (19.0, 28.3)25.9 (20.5, 32.0)Grade 3/4 bone pain, % (95% CI) All cycles4.8 (2.8, 7.5)6.7 (4.0, 10.6)Cycle 12.8 (1.4, 5.1)4.4 (2.2, 7.7)Cycle 20.9 (0.2, 2.5)0.8 (0.1, 2.9)Cycle 31.2 (0.3, 3.0)2.0 (0.7, 4.7)Cycle 40.6 (0.1, 2.2)1.3 (0.3, 3.6)CI = Confidence intervalConclusions: Bone pain incidence was similar for the pegfilgrastim and filgrastim arms. Bone pain of any grade was common in these breast cancer patients receiving taxane-containing chemotherapy with growth factor support. Bone pain may be associated with a combination of disease state (including metastatic site), co-morbid conditions (eg, arthritis), chemotherapy, and growth factor use. Severe bone pain can occur; however, this was infrequently reported in these patients. In both treatment arms, bone pain incidence was most frequent in the first cycle of chemotherapy. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1117.

Randomized Trial and Pharmacokinetic Study of Pegfilgrastim versus Filgrastim after Dose-Intensive Chemotherapy in Young Adults and Children with Sarcomas

To compare the effectiveness, tolerance, and pharmacokinetics of a single dose of pegfilgrastim to daily filgrastim in children and young adults with sarcomas treated with dose-intensive combination chemotherapy. Patients were randomized to receive a single dose of 100 mcg/kg of pegfilgrastim s.c. or 5 mcg/kg/day of filgrastim s.c., daily until neutrophil recovery after two treatment cycles with vincristine, doxorubicin, and cyclophosphamide (VDC) and two cycles of etoposide and ifosfamide (IE). The duration of severe neutropenia (absolute neutrophil count, < or =500/mcL) during cycles 1 to 4 and cycle duration for all cycles were compared. Pharmacokinetics of pegfilgrastim and filgrastim and CD34+ stem cell mobilization were studied on cycle 1. Growth factor-related toxicity, transfusions, and episodes of fever and neutropenia and infections were collected for cycles 1 to 4. Thirty-four patients (median age, 20 years; range 3.8-25.8) were enrolled, and 32 completed cycles 1 to 4. The median (range) duration of absolute neutrophil count of <500/mcL was 5.5 (3-8) days for pegfilgrastim and 6 (0-9) days for filgrastim (P = 0.76) after VDC, and 1.5 (0-4) days for pegfilgrastim and 3.75 (0-6.5) days for filgrastim (P = 0.11) after IE. More episodes of febrile neutropenia and documented infections occurred on the filgrastim arm. Serum pegfilgrastim concentrations were highly variable. Pegfilgrastim apparent clearance (11 mL/h/kg) was similar to that reported in adults. A single dose per cycle of pegfilgrastim was well tolerated and may be as effective as daily filgrastim based on the duration of severe neutropenia and number of episodes of febrile neutropenia and documented infections after dose-intensive treatment with VDC and IE.

Reported Bone Pain in Cancer Patients Receiving Chemotherapy in Pegfilgrastim Clinical Trials: A Retrospective Analysis.

Abstract 4561 BackgroundMild to moderate bone pain is the most commonly reported treatment-related adverse event (AE) associated with administration of granulocyte colony-stimulating factors (G-CSFs). There is a perception that bone pain associated with pegfilgrastim (the pegylated form of filgrastim) occurs at a higher frequency, is more severe, and is less predictable than bone pain associated with filgrastim. To evaluate this hypothesis, a retrospective analysis examining bone pain in cancer patients receiving chemotherapy in pegfilgrastim clinical trials was conducted. MethodsData analyzed were from 12 sponsor-supported trials of once per chemotherapy cycle pegfilgrastim (6 mg fixed dose or 100 mcg/kg) versus daily filgrastim (5 mcg/kg) or versus no G-CSF administered following chemotherapy in patients with non-Hodgkin's lymphoma (NHL), breast, lung, colorectal, or ovarian cancer. The AEs reported were coded according to MedDRA (version 11) and the preferred terms considered to include bone pain were determined prior to analysis. Incidences of any grade and grade 3/4 bone pain were calculated by treatment (pegfilgrastim, filgrastim, or no G-CSF) and chemotherapy cycle. ResultsData for patients who received pegfilgrastim (n=1498), filgrastim (n=354) or no G-CSF (n=1102) were included in this analysis. In the 7 studies comparing pegfilgrastim (n=377) with filgrastim (n=354) in patients with NHL, breast or lung cancer, similar proportions of patients reported bone pain of any grade (Table 1). In both treatment arms, bone pain incidence was highest in the first cycle of chemotherapy and decreased in subsequent cycles. In both the pegfilgrastim and filgrastim arms, grade 3/4 bone pain incidence was low across all cycles (6.6% and 7.9%, respectively), in the first cycle (4.2% and 5.4%, respectively), and in subsequent cycles (Table 1). In the 5 studies comparing pegfilgrastim (n=1121) with no G-CSF (n=1102) in patients with NHL, breast, lung, colorectal, or ovarian cancer, 74% of the patients were female, 78% were white and the median (minimum, maximum) age was 65 (18, 88) years. Of these patients, 53% had breast cancer and 68% received a taxane-based regimen. Three of the 5 studies allowed pegfilgrastim use after cycle 1 in the control arm (ie, secondary prophylaxis); therefore, only cycle 1 bone pain incidences were compared for this analysis. The proportion (confidence interval [CI]) of patients who reported bone pain in the first cycle of chemotherapy was higher in the pegfilgrastim arm than the no G-CSF arm; 32.7% (30.0%, 35.6%) versus 23.0% (20.6%, 25.7%). Grade 3/4 bone pain was infrequently reported in these patients (3.4% [2.4%, 4.6%] pegfilgrastim, 2.0% [1.3%, 3.0%] no G-CSF). ConclusionsIn this analysis, bone pain was common in cancer patients receiving chemotherapy, and was most frequently reported in the first cycle of treatment. Bone pain incidences were similar for the pegfilgrastim and filgrastim arms and slightly higher in the pegfilgrastim than in the no G-CSF arm. Bone pain may be associated with a combination of factors including disease state (eg, metastatic site), co-morbid conditions (eg, arthritis, osteoporosis), type of chemotherapy received, and growth factor use. Severe bone pain can and does occur in this population; however, this was infrequently reported in the studies included in this analysis.Table 1Demographics and bone pain incidence in cancer patients receiving pegfilgrastim or filgrastimOnce Per Cycle Pegfilgrastim n=377Daily Filgrastim n=354Female, n (%)317 (84)298 (84)White, n (%)319 (85)303 (86)Age, median years (min, max)52 (21, 82)54 (20, 87)Primary tumor type, n (%)Breast279 (74)255 (72)NHL78 (21)73 (21)NSCL20 (5)26 (7)Received a taxane, n (%)299 (79)281 (79)Bone pain, any grade, % (95% CI), [n]All cycles62.3 (57.2, 67.2) [377]66.1 (60.9, 71.0) [354]Cycle 146.2 (41.0, 51.3) [377]51.7 (46.4, 57.0) [354]Cycle 230.9 (26.1, 36.1) [349]32.5 (27.6, 37.8) [338]Cycle 324.8 (20.2, 29.8) [327]27.6 (22.6, 33.0) [301]Cycle 423.7 (19.2, 28.8) [316]24.3 (19.5, 29.7) [288]Grade 3/4 bone pain, % (95% CI), [n]All cycles6.6 (4.3, 9.6) [377]7.9 (5.3, 11.2) [354]Cycle 14.2 (2.4, 6.8) [377]5.4 (3.3, 8.3) [354]Cycle 20.9 (0.2, 2.5) [349]1.8 (0.7, 3.8) [338]Cycle 30.9 (0.2, 2.7) [327]2.0 (0.7, 4.3) [301]Cycle 41.3 (0.3, 3.2) [316]1.4 (0.4, 3.5) [288]CI = confidence interval; NHL = Non Hodgkin's lymphoma; NSCL = non-small cell lung Disclosures:Gregory:Amgen: Consultancy. Mo:Amgen: Employment, Equity Ownership. Vogel:Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau; GSK: Consultancy, Honoraria, Research Funding, Speakers Bureau; Genentech: Consultancy, Honoraria, Research Funding, Speakers Bureau; EMD Serono: Consultancy, Honoraria, Research Funding, Speakers Bureau; Astra Zeneca: Consultancy, Speakers Bureau; Roche: Consultancy, Speakers Bureau; Pfizer: Consultancy, Research Funding, Speakers Bureau; Norvatis: Consultancy, Research Funding, Speakers Bureau; BMS: Consultancy, Honoraria, Speakers Bureau; Sanofi Aventis: Consultancy, Honoraria; Ortho Biotech: Consultancy, Speakers Bureau. Schwartzberg:Amgen: Speakers Bureau; GSK: Speakers Bureau; BMS: Speakers Bureau.

Incidence of Febrile Episodes During Stem Cells Mobilization After High Dose Cyclophosphamide Chemotherapy and G-CSF (filgrastim or lenograstim) Administration in Multiple Myeloma Patients: Preliminary Final Results.

Abstract 4560 IntroductionThe G-CSF, primary regulator of granulopoiesis, has shown its efficacy in reducing duration of neutropenia after chemotherapy or myelosuppressive therapy. In these situations G-CSF, accelerating the granulocytous reconstitution, may enable a significant reduction of the incidence, duration and severity of infection. Commercially formulations of rHu-G-CSF include lenograstim, a glycosylated form, and filgrastim, a non-glycosylated form. Glycosylation of the molecule contribute to pharmacokynetis advantages and to higher affinity to specific receptor. Additionally, lenograstim exposed neutrophils maintain unchanged all their functions in vitro, while filgrastim exposed neutrophils present functional defects due to higher adhesivity, cytoscheletric alterations and a more immature phenotype. AimOn these bases, we hypotized that lenograstim may prevent febrile episodes (FE) and reduce their lasting in patients with chemotherapy derived neutropenia more efficiently than filgrastim. Primary endpoint is the incidence of FE (ClinicalTrials.gov ID: NCT00932217). Patients and methodsstarting from April 2005, 180 multiple myeloma patients achieving high dose cyclophosphamide for stem cells mobilization were enrolled in 11 Italian Centers. Treatment plan consisted in: high dose cyclophosphamide (3 or 4 g/sqm) on day 1, G-CSF (random 1:1 on the base of a generated random list: filgrastim or lenograstim) 30 MU/day from day +4 to +9, 60 MU/day from day +10 to the achievement of an optimal CD34+ cell count for staminoapheresis. FE, significant if equal or higher than 38 °C for at least 2 different determinations, were recorded till day +30. Results176 of 180 patients received scheduled treatment and are eligible for final analyses. All 176 patients underwent post-chemo grade 4 neutropenia and G-CSF was administered starting from day +4. FE were recorded in 26 pts, 16 in the filgrastim arm (89 total patients) and 10 in the lenograstim arm (87 total patients). The global fever incidence was 14.77%, 17.98% with filgrastim and 11.49% with lenograstim. However, to demonstrate functional block of filgrastim exposed neutrophils, FE have been related to neutrophil absolute count. Related to the neutropenia grade, 8 FE are recorded with filgrastim (8.99%) and 1 FE with lenograstim (1.15%) with absolute neutrophil count >500/μL (grade 3) (chi square test with Yates' correction: p=0.0436); this difference is still evident when neutrophils are >1000/μL (grade 2), with 7 episodes with filgrastim (7.87%) versus 1 (1.15%) with lenograstim. ConclusionsLenograstim is associated with a reduced global incidence of FE in multiple myeloma patients undergoing to high dose cyclophosphamide and stem cells mobilization when compared to filgrastim. Additionally, excluding the time frame when neutrophils are not yet recovered (neutrophils <500/μL; grade 4 neutropenia) and G-CSF effects may not be demonstrated, filgrastim treated patients present, when compared to lenograstim treated patients, an higher FE incidence at neutrophil absolute count recovery (both with grade 3 and grade 2 neutropenia), confirming the functional block of filgrastim exposed neutrophils described in vitro. On the contrary, lenograstim allows to recovery normally functional neutrophils as demonstrated by the very low incidence of FE (1.15% with neutrophils >500/μL) in treated patients. Disclosures:No relevant conflicts of interest to declare.

A comparative study of single-dose pegfilgrastim versus daily filgrastim in patients with acute myeloid leukemia

e18005 Background: Prophylactic treatment with recombinant human granulocyte colony stimulating factor (rhGCSF) is used to decrease the severity and duration of neutropenia in patients receiving myelosupressive chemotherapy. It can be used during induction and consolidation chemotherapy in acute myeloid leukemia (AML). Mechanism of action of pegylated GCSF is the same as filgrastim except for delayed clearance. Few studies addressed the use of pegylated filgrasim in AML. Methods: After 24 hours of consolidation chemotherapy, 8 patients in the study arm received single dose of subcutaneous 6 mg pegfilgrastim. The control group received daily filgrastim at a dose of 5 microgram per kg.until absolute neutroophil count of 2 ×109 cells/μL for 2 consecutive days. The neutrophil recovery time, febrile neutropenia and its duration, duration of hospitalization and safety profiles were compared. Results: There were 20 episodes of pegfilgrastim administration. The median age was 41 years in pegfilgrastim arm and 39 years in filgrastim arm. Medium time to neutrophil recovery was 14 days for pegfilgrastim arm and 17 days for filgrastim arm. In the pegfilgrastim arm 12 (60%) episodes of febrile neutropenia occurred compared to 11 (55%) in filgrastim arm. The median duration of febrile neutropenia was 3 days in pegfilgrastim arm versus 4 days in filgrastim arm. The median duration of hospitalization was 15 days in pegfilgrastim arm and 18 days in filgrastim arm. Safety profile and complete remission status did not differ between the two groups. Conclusions: The present study showed favorable profile of pegfilgrastim for netrophil recovery, duration of neutropenia and hospital stay. There was no difference with regard to safety or response to treatment. No significant financial relationships to disclose.

Randomized phase II trial of three dosing schedules of nanoparticle albumin-bound paclitaxel with bevacizumab as first-line therapy for HER2-negative metastatic breast cancer: An initial interim safety report

1104 Background: Nanoparticle paclitaxel (NP) at 260mg/m2 every 3 weeks (q3wk) is more effective than standard paclitaxel (P) (Gradishar et al, JCO 2005). Weekly, uninterrupted administration of P is superior to q3wk P in MBC (Seidman et al, Proc ASCO 2004). When added to weekly P as 1st-line therapy for MBC, bevacizumab (B) improves response rate and progression-free survival (Miller et al, Proc ASCO 2005). We initiated a randomized phase II trial of NP given at 260mg/m2 q3wk (arm A) vs. 260mg/m2 q2wk with filgrastim (arm B) vs. 130mg/m2 weekly, all with B, as 1st-line therapy for patients (pts) with HER2- MBC. Methods: 66 of planned 225 pts have enrolled. After 31 pts had been randomized and treated, investigators concerned about possible differential neurotoxicity requested this early interim safety analysis. Median age is 54 (range 40–78). 83% are post-menopausal and 100% have visceral dominant disease. 68% had prior adjuvant or neo-adjuvant chemotherapy; 35% with taxanes. Results: With 170 cycles delivered (median: 4, range 1–15) 10 dose reductions have been necessary for NP (1 in A, 5 in B, 4 in C). No hypersensitivity reactions or dose interruptions have occurred for NP; 3 doses of B have been held due to hypertension. Significant preliminary antitumor activity has been noted in all arms. One grade 4 toxicity occurred in arm C, hyperglycemia. 15 grade 3 toxicities have been reported across all arms. Pts on arm A have experienced 3 grade 3 toxicities (30%): fatigue, neutropenia, and arthralgia with no grade 3 neurotoxicity. Pts on arm B have had 7 grade 3 toxicities (58%) with 3 pts experiencing grade 3 sensory neuropathy (25%) and others experiencing fatigue, neutropenia, anemia, esophagitis, dyspnea, and ataxia. 5 arm C pts experienced grade 3 toxicities (56%) including diarrhea, dehydration, mucositis, neutropenia, hypokalemia; 2 pts have had grade 3 sensory neuropathy (22%). Conclusions: This early safety analysis does not detect any statistically or clinically significant differences in grade 3 toxicity and all arms continue to accrue. The next protocol-specified safety analysis is expected in early 2007, with mature safety data for 60 pts. Updated results will be presented. [Table: see text]

A randomized study comparing filgrastim versus lenograstim versus molgramostim plus chemotherapy for peripheral blood progenitor cell mobilization

We conducted a prospective randomized clinical trial to assess the mobilizing efficacy of filgrastim, lenograstim and molgramostim following a disease-specific chemotherapy regimen. Mobilization consisted of high-dose cyclophosphamide in 45 cases (44%), and cisplatin/ifosfamide/etoposide or vinblastine in 22 (21%), followed by randomization to either filgrastim or lenograstim or molgramostim at 5 microg/kg/day. One hundred and three patients were randomized, and 82 (79%) performed apheresis. Forty-four (43%) patients were chemonaive, whereas 59 (57%) were pretreated. A median number of one apheresis per patient (range, 1-3) was performed. The median number of CD34+ cells obtained after mobilization was 8.4 x 10(6)/kg in the filgrastim arm versus 5.8 x 10(6)/kg in the lenograstim arm versus 4.0 x 10(6)/kg in the molgramostim arm (P=0.1). A statistically significant difference was observed for the median number of days of growth factor administration in favor of lenograstim (12 days) versus filgrastim (13 days) and molgramostim (14 days) (P<0.0001) and for the subgroup of chemonaive patients (12 days) versus pretreated patients (14 days) (P<0.001). In conclusion, all three growth factors were efficacious in mobilizing peripheral blood progenitor cells with no statistically significant difference between CD34+ cell yield and the different regimens, and the time to apheresis is likely confounded by the different mobilization regimens.