Efficacy and safety of lipegfilgrastim compared with pegfilgrastim in patients with breast cancer who are receiving chemotherapy.

e19587 Background: Cancer chemotherapy frequently causes neutropenia, leading to an increased risk of infections and delays in subsequent chemotherapy treatments. Pegfilgrastim is a pegylated recombinant form of granulocyte colony stimulating factor (G-CSF) that extends the half-life and requires less frequent dosing than nonpegylated G-CSF. Lipegfilgrastim is a glycosylated and pegylated G-CSF. The objective of this study was to compare the efficacy and safety of lipegfilgrastim and pegfilgrastim in chemotherapy-naïve patients with breast cancer who are candidates to receive docetaxel/doxorubicin. Methods: In this double-blind, randomized, active-controlled, noninferiority trial, patients with high-risk stage II, III, or IV breast cancer and an absolute neutrophil count ≥1.5x109 cells/L were randomly assigned to lipegfilgrastim 6 mg (n=101) or pegfilgrastim 6 mg (n=101). Study medication was injected subcutaneously on day 2 of the chemotherapy cycle (4 cycles maximum). Primary efficacy endpoint was the duration of severe neutropenia (days with an absolute neutropenia count <0.5x109 cells/L) during cycle 1. Secondary endpoints included the incidence of febrile neutropenia. Efficacy analysis population included patients who were randomized but did not have major protocol violations. Results: Overall, 37%, 46%, and 17% of patients had stage II, III, and IV breast cancer, respectively. The mean duration of severe neutropenia in cycle 1 was 0.7 days in the lipegfilgrastim group and 0.8 days in the pegfilgrastim group (poisson regression least squares mean [95% CI] -0.218 [-0.498 to 0.062]). 56% and 49%, respectively, did not experience severe neutropenia in cycle 1. Three patients experienced febrile neutropenia; all were in the pegfilgrastim group during cycle 1. 28% of patients in the lipegfilgrastim group and 26% in the pegfilgrastim group had adverse events that the investigator considered to be related to study medication. Three and 7 patients, respectively had serious adverse events. Conclusions: The results of this study confirm that the efficacy of lipegfilgrastim is comparable with pegfilgrastim. No unexpected safety events were observed.

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Efficacy and safety of balugrastim compared with pegfilgrastim in patients with breast cancer who are receiving chemotherapy.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.9125 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 9125-9125 ◽

Cited By ~ 1

Author(s):

Constantin D. Volovat ◽

Oleg Gladkov ◽

Igor Bondarenko ◽

Steven Barash ◽

Anton Buchner ◽

...

Keyword(s):

Breast Cancer ◽

Febrile Neutropenia ◽

Adverse Events ◽

Severe Neutropenia ◽

Comparable Efficacy ◽

Efficacy And Safety ◽

Serious Adverse Events ◽

Double Blind ◽

Increased Risk ◽

Long Acting

9125 Background: Patients receiving cancer chemotherapy are at an increased risk of neutropenia. Recombinant granulocyte colony stimulating factors (G-CSFs) have been developed to stimulate proliferation and differentiation of neutrophils. Pegfilgrastim is a pegylated recombinant G-CSF that allows for once-per-cycle dosing. Balugrastim is a long-acting G-CSF composed of a genetic fusion between recombinant human serum albumin and G-CSF. The objective of this study was to compare the efficacy and safety of balugrastim and pegfilgrastim in patients with histologically or cytologically confirmed breast cancer who were scheduled to receive doxorubicin and docetaxel. Methods: In this double-blind, randomized, active-comparator, noninferiority trial, patients with ≥1.5x109 neutrophils/L, and ≥100x109 platelets/L were randomly assigned to subcutaneous injections of balugrastim 40 mg (n=153) or pegfilgrastim 6 mg (n=151) with stratifications for weight, prior chemotherapy exposure, and global location. The primary efficacy endpoint was the duration of severe neutropenia (days with an absolute neutrophil count <0.5x109 cells/L) during the cycle 1 for the population of patients who did not have major protocol violations. Results: Mean duration of severe neutropenia in cycle 1 was 1.1 days in the balugrastim group and 1.0 days in the pegfilgrastim group (95% CI for difference between groups -0.13 to 0.37). Fifty-eight percent of patients in the balugrastim group and 59% in the pegfilgrastim group had severe neutropenia during cycle 1 (95% CI for difference between groups -11.98% to 10.41%). Two and 4 patients, respectively, had febrile neutropenia during cycle 1; no patients in either group had febrile neutropenia during cycles 2-4. Twenty percent of patients in the balugrastim group and 19% in the pegfilgrastim group had adverse events that the investigator considered to be related to study medication. Six and 7 patients, respectively, had serious adverse events. Conclusions: The results of this study support the noninferiority of balugrastim versus pegfilgrastim, demonstrating that both compounds have comparable efficacy. There were no unexpected safety events.

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Sertraline in the treatment of panic disorder

The British Journal of Psychiatry ◽

10.1192/bjp.173.1.54 ◽

1998 ◽

Vol 173 (1) ◽

pp. 54-60 ◽

Cited By ~ 87

Author(s):

Peter D. Londborg ◽

Robert Wolkow ◽

Ward T. Smith ◽

Eugene Duboff ◽

Donald England ◽

...

Keyword(s):

Panic Disorder ◽

Adverse Events ◽

Drop Out ◽

Panic Attacks ◽

Efficacy And Safety ◽

Serious Adverse Events ◽

Double Blind ◽

Hamilton Anxiety Scale ◽

Higher Doses ◽

Clinical Global Impression Improvement

BackgroundThis study compared the efficacy and safety of sertraline to placebo in treating panic disorder.Method178 out-patients with panic disorder who exhibited at least four panic attacks during the four weeks prior to screening and three during the two weeks of lead-in were randomly assigned to 12 weeks of double-blind treatment with sertraline (50, 100 or 200 mg) or placebo.ResultsSertraline was superior to placebo in reducing the number of panic attacks, situational attacks, unexpected attacks, limited symptom attacks, and time spent worrying (all P < 0.01) and the Hamilton Anxiety Scale (P < 0.05), although Clinical Global Impression (Improvement) did not significantly differentiate groups at 12 weeks and at end-point. No serious adverse events were associated with sertraline. No dose relationship was found for adverse events; overall drop-out rates were not different for sertraline or placebo, although more sertraline-treated subjects discontinued for adverse events, typically early in the study. Only dry mouth and ejaculation failure (primarily ejaculation delay) were associated significantly with sertraline. Conclusions Sertraline was effective and safe in reducing panic attacks. Higher doses were no more effective than the 50 mg dose.

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Duloxetine in the Treatment of Stress Urinary Incontinence

Women s Health ◽

10.2217/17455057.1.3.345 ◽

2005 ◽

Vol 1 (3) ◽

pp. 345-358 ◽

Cited By ~ 6

Author(s):

Martin C Michel ◽

Matthias Oelke

Keyword(s):

Urinary Incontinence ◽

Stress Urinary Incontinence ◽

Adverse Events ◽

Striated Muscle ◽

Bladder Capacity ◽

Efficacy And Safety ◽

Cytochrome P450 1A2 ◽

Serious Adverse Events ◽

Double Blind ◽

Urethral Striated Muscle

This manuscript reviews the pharmacodynamics and pharmacokinetics of duloxetine and its efficacy and safety in women with stress urinary incontinence. Duloxetine is a selective inhibitor of neuronal serotonin and norepinephrine uptake which increases urethral striated muscle activity and bladder capacity. Duloxetine is readily absorbed and extensively metabolized; cytochrome P450 1A2 (CYP1A2) inhibiting drugs can markedly increase duloxetine exposure. The clinical efficacy of duloxetine has consistently been demonstrated in several randomized, double-blind studies in women with moderate-to-severe stress urinary incontinence, but the additional benefit relative to placebo was moderate. Duloxetine treatment is frequently associated with adverse events such as nausea, dry mouth, fatigue, insomnia and constipation, but serious adverse events are rare. Therefore, duloxetine appears suitable for the treatment of stress urinary incontinence.

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P.027 Efficacy and Safety of Eptinezumab Initiated During a Migraine Attack: Results from the RELIEF Study

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/cjn.2021.309 ◽

2021 ◽

Vol 48 (s3) ◽

pp. S27-S28

Author(s):

PK Winner ◽

P McAllister ◽

G Chakhava ◽

J Ailani ◽

L Mehta ◽

...

Keyword(s):

Adverse Events ◽

Migraine Attack ◽

Rapid Onset ◽

Migraine Treatment ◽

Efficacy And Safety ◽

Serious Adverse Events ◽

Double Blind ◽

Bothersome Symptom ◽

Post Infusion ◽

Headache Pain

Background: Eptinezumab is approved for migraine prevention, with demonstrated rapid onset of preventive benefit. RELIEF evaluated the efficacy and safety of eptinezumab initiated during a migraine attack. Methods: RELIEF (NCT04152083; parallel-group, double-blind, placebo-controlled) randomized adults with migraine (4-15d/mo in 3mo prior to screening) to eptinezumab 100mg or placebo, administered IV within 1-6h of qualifying migraine onset. Co-primary efficacy endpoints were time to headache pain freedom and time to absence of most bothersome symptom (MBS). Results: Eptinezumab (n=238) compared with placebo (n=242) achieved significantly faster headache pain freedom (median 4h vs 9h; hazard ratio=1.54, P=0.0006) and absence of MBS (2h vs 3h; 1.75, P<0.0001). At 2h, 23.5% and 12.0% (P=0.0009) of eptinezumab-treated and placebo patients, respectively, reported headache pain freedom, and 55.5% and 35.8% (P<0.0001) reported absence of MBS. Significantly fewer eptinezumab-treated patients used rescue medication within 24h (31.5% vs 59.9%; P<0.0001). Treatment-emergent adverse events occurred in 10.9% eptinezumab-treated and 10.3% placebo patients; no serious adverse events occurred. Conclusions: Infusion of the preventive migraine treatment, eptinezumab, during a migraine resulted in rapid and sustained freedom from headache pain and MBS vs placebo, starting 2h post-infusion, decreasing need for acute medication within 24h post-infusion. No notable safety findings were identified.

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Inclusion of Platinum Agents in Neoadjuvant Chemotherapy Regimens for Triple-Negative Breast Cancer Patients: Development of GRADE (Grades of Recommendation, Assessment, Development and Evaluation) Recommendation by the Italian Association of Medical Oncology (AIOM)

Cancers ◽

10.3390/cancers11081137 ◽

2019 ◽

Vol 11 (8) ◽

pp. 1137 ◽

Cited By ~ 4

Author(s):

Maria Vittoria Dieci ◽

Lucia Del Mastro ◽

Michela Cinquini ◽

Filippo Montemurro ◽

Laura Biganzoli ◽

...

Keyword(s):

Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Febrile Neutropenia ◽

Adverse Events ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Medical Oncology ◽

Serious Adverse Events ◽

Assessment Development ◽

Grade 3

In the absence of identified therapeutic targets, chemotherapy is the main systemic treatment option for triple-negative breast cancer (TNBC). The achievement of a pathological complete response (pCR) after neoadjuvant chemotherapy leads to good outcome, whereas patients not achieving a pCR are at high risk of relapse. Various trials have evaluated the inclusion of platinum in neoadjuvant chemotherapy regimens for TNBC, leading to non-univocal results. The panel of the Italian Association of Medical Oncology (AIOM) Guidelines on Breast Cancer developed a clinical recommendation on the addition of platinum to anthracycline/taxane-based neoadjuvant chemotherapy for TNBC by using the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) methodology and the Evidence to Decision framework (EtD). Five studies were eligible. The panel identified the following outcomes of benefit: pCR (critical), disease/event-free survival (DFS/EFS, critical), and overall survival (OS, critical). The panel identified febrile neutropenia (critical), serious adverse events (critical), anemia grade 3–4 (important), thrombocytopenia grade 3–4 (important) as outcomes of harms. The probability of pCR was higher in the platinum-based chemotherapy group versus control group (RR = 1.45, 95%CI 1.28–1.64); however, no impact on long-term outcome was observed. Neoadjuvant treatment regimens containing platinum resulted in a non-significant increase in the risk of febrile neutropenia and in a significant increase in the risk serious adverse events, G3–G4 anemia and G3–G4 thrombocytopenia: 11.3% versus 0.8%, RR = 15.66 (95%CI 6.38–38.44). The panel judged uncertain/favorable the benefit/harms balance. The panel’s final recommendation was conditional in favor of the inclusion of platinum in anthracycline/taxane-based neoadjuvant regimens for TNBC.

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A Comparison of Proposed Biosimilar and Originator Filgrastim for the Prevention of Neutropenia in Patients with Breast Cancer Receiving Myelosuppressive Adjuvant or Neoadjuvant Chemotherapy: Phase III, Randomized, Double-Blind Trial (The PIONEER study)

Blood ◽

10.1182/blood.v124.21.5133.5133 ◽

2014 ◽

Vol 124 (21) ◽

pp. 5133-5133 ◽

Cited By ~ 4

Author(s):

Kimberly Blackwell ◽

Vladimir Semiglazov ◽

Pedro Gascon ◽

Roumen Nakov ◽

Stefan Kramer ◽

...

Keyword(s):

Breast Cancer ◽

Treatment Group ◽

Adverse Events ◽

Lower Limit ◽

Study Drug ◽

Phase Iii ◽

Efficacy And Safety ◽

Double Blind ◽

Pioneer Study ◽

The Mean

Abstract Introduction: Biosimilars are biologics which have demonstrated highly similar safety, potency and purity to an originator product. Several biosimilars of recombinant human filgrastim, based on the originator Neupogen®, have become available in Europe since 2008 and are now in clinical use for the prevention of chemotherapy-induced neutropenia and hematopoietic stem cell mobilization. Filgrastim biosimilars are presently being developed for the U.S. market. Study design: A randomized, double-blind, four-group, multi-center phase III non-inferiority trial was performed with breast cancer patients treated with myleosuppressive chemotherapy. The two filgrastim products – proposed biosimilar, EP2006 (“biosimilar”) vs. originator (U.S.-licensed Neupogen®) - were compared regarding efficacy and safety. Patients included: women ≥18 years with histologically-proven breast cancer eligible for neoadjuvant or adjuvant treatment with docetaxel 75 mg/m2, doxorubicin 50 mg/m2 and cyclophosphamide 500 mg/m2 (TAC regimen) given for 6 cycles. Other key inclusion criteria included: Eastern Cooperative Oncology Group performance status ≤2 and adequate bone marrow function. Eligible patients were randomized to 4 groups with 2 of these groups alternating between the biosimilar and the originator filgrastim at the end of each cycle: 1) EP: treatment with EP2006 in all cycles; 2) EPNEU: EP2006 in Cycle 1, alternating between Neupogen and EP2006 in the following cycles; 3) NEUEP: Neupogen in Cycle 1, alternating between EP2006 and Neupogen in the following cycles; 4) NEU: treatment with Neupogen in all cycles. Patients received either biosimilar or originator filgrastim subcutaneously (daily dose of 5 µg/kg body weight) starting on Day 2 of each chemotherapy cycle until the absolute neutrophil count (ANC) recovered to 10×109/L after nadir or up to 14 days. Total duration of the study was 25 weeks: 3 weeks screening, 18 weeks treatment (total 6 cycles, 3 weeks each) and a follow-up visit 4 weeks after the last study drug administration. Primary objective was to assess the efficacy of the biosimilar compared to the originator with respect to mean duration of severe neutropenia (DSN) following Cycle 1 chemotherapy. A one-sided 97.5% confidence interval (CI) for the difference in the mean DSN calculated using ANCOVA model with factors “treatment” and “kind of therapy” and covariates “baseline ANC” was to be considered non-inferior if lower limit of this CI lies entirely above non-inferiority margin of -1 day. All secondary efficacy endpoints and safety endpoints were analyzed descriptively by treatment group. The study was conducted between December 2011 and June 2013. Results: Enrolled were 258 patients in 27 centers, of which 218 patients were randomized to treatment. The baseline characteristics were balanced between different groups. The per-protocol set included 204 patients out of 218 randomized patients. The safety set included 214 patients who received at least one dose of study drug. On average each patient received treatment for 8-9 days per cycle. The mean DSN in Cycle 1 was 1.17±1.11 days (biosimilar) and 1.20±1.02 days (originator); the mean difference in DSN was 0.04 days (97.5% CI, lower limit -0.26 days). The pre-defined non-inferiority criteria were met and the biosimilar was considered non-inferior to the originator filgrastim. The incidence of febrile neutropenia over all 6 cycles chemotherapy was comparably low in all treatment groups (EP: 2/40, 5.0%, EPNEU: 5/45, 11.1%, NEUEP: 1/44, 2.3%, NEU: 0/46, 0.0%). There was no obvious difference in incidences of treatment emergent adverse events between the treatment arms. Twelve patients experienced serious adverse events (EP: 5/53, 9.4% patients; EPNEU: 4/54, 7.4%; NEUEP: 1/55, 1.8%; NEU: 2/52, 3.8%). None of them were study drug related, including one death (in the EP treatment group due to pulmonary embolism). No subjects developed anti-drug antibodies. Conclusion: This large clinical study showed that efficacy and safety of the biosimilar was comparable to the originator filgrastim in prevention of neutropenia in patients with breast cancer. Repeated switching between the biosimilar and the originator filgrastim did not impact efficacy, safety or immunogenicity. Acknowledgment: The authors acknowledge the other investigators of the PIONEER study and acknowledge Gabor Stiegler, Sandoz Biopharmaceuticals for the medical writing. Disclosures Blackwell: Sandoz Biopharmaceuticals: Consultancy. Semiglazov:Sandoz Biopharmaceuticals: Consultancy. Gascon:Sandoz Biopharmaceuticals: Consultancy. Nakov:Sandoz Biopharmaceuticals: Employment. Kramer:Sandoz Biopharmaceuticals: Employment. Schwebig:Sandoz Biopharmaceuticals: Employment. Harbeck:Sandoz Biopharmaceuticals: Consultancy.

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Safety and Efficacy of Ranibizumab and Bevacizumab for the Treatment of Neovascular Age-related Macular Degeneration

European Ophthalmic Review ◽

10.17925/eor.2012.06.01.34 ◽

2012 ◽

Vol 06 (01) ◽

pp. 34 ◽

Cited By ~ 1

Author(s):

Victor Chong ◽

Peter K Kaiser ◽

Paul Mitchell ◽

◽

...

Keyword(s):

Adverse Events ◽

Macular Degeneration ◽

Half Life ◽

Safety Data ◽

Significant Risk ◽

Age Related Macular Degeneration ◽

Efficacy And Safety ◽

Serious Adverse Events ◽

Age Related ◽

Increased Risk

Ocular anti-vascular endothelial growth factor (VEGF) therapy represents a major breakthrough in the treatment of patients with neovascular age-related macular degeneration (nvAMD). The anti-VEGF agents, ranibizumab and bevacizumab, are both widely used in the treatment of nvAMD although bevacizumab has not yet received regulatory approval for intraocular use. Bevacizumab costs considerably less than ranibizumab when administered as an intraocular injection, which has led to widespread use and studies comparing the efficacy and safety of the two drugs. Bevacizumab shares identical pharmacology with ranibizumab although structural differences result in differences in receptor affinity and rates of drug clearance. While estimates of the vitreous half-life of ranibizumab vary, it is shorter than that of bevacizumab. Furthermore, the serum half-life of bevacizumab is about 20 days, more than twice that of ranibizumab and this has led to speculation that it may present a greater risk of systemic adverse effects. Considerable clinical trial evidence exists relating to the efficacy and safety of ranibizumab. The Comparison of age-related macular degeneration treatments trials (CATT) study of the two drugs found efficacy to be equivalent for the as needed versus as needed and monthly versus monthly comparisons. Ranibizumab as needed was equivalent to monthly ranibizumab, though the bevacizumab as needed was not equivalent to monthly bevacizumab. A greater number of serious adverse events (SAEs) occurred with bevacizumab. However, the study was insufficiently powered to identify differences in drug-related adverse events. Intravitreal injection of bevacizumab is associated with a low but significant risk of acute intraocular inflammation, shown to result in significant visual loss in some patients. Finally, there are issues related to fractionating of bevacizumab that has lead to sporadic cases of blindness worldwide. The increased risk for both systemic and ocular adverse events may influence the cost-effectiveness ratio of the two drugs based on health economic models. Further comparative studies and continuous monitoring of safety data are required to examine the incidence of adverse events.

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Proposed Biosimilar Pegfilgrastim (LA-EP2006) and Reference Pegfilgrastim for the Prevention of Neutropenia in Patients with Breast Cancer: A Randomized, Double-Blind Trial. Protect 2: Pegfilgrastim Randomized Oncology (supportive care) Trial to Evaluate Comparative Treatment Results

Blood ◽

10.1182/blood.v126.23.632.632 ◽

2015 ◽

Vol 126 (23) ◽

pp. 632-632

Author(s):

Kimberley Blackwell ◽

Ruslan Paltuev ◽

Roman Donskih ◽

Olga Burdaeva ◽

Elena Bit-Sava ◽

...

Keyword(s):

Breast Cancer ◽

Febrile Neutropenia ◽

Primary Endpoint ◽

Research Funding ◽

Severe Neutropenia ◽

Infection Frequency ◽

Double Blind Trial ◽

Double Blind ◽

Blind Trial ◽

Tac Chemotherapy

Abstract Background: Approval of a biosimilar is based on it being highly similar with regard to safety, purity, and potency and with no clinically meaningful differences when compared with a reference product.The first biosimilar, filgrastim (EP-2006), was recently approved in US.LA-EP2006 is a proposed biosimilar to the reference product pegfilgrastim (Neulasta®). Methods: This was a prospective, randomized, double-blind trial conducted in the US, Latin America, Asia and Europe. Patients with histologically proven breast cancer receiving (neo)-adjuvant TAC chemotherapy (docetaxel 75mg/m2, doxorubicin 50mg/m2, cyclophosphamide 500mg/m2) over six cycles were treated with a single 6mg SC injection of LA-EP2006 or reference pegfilgrastim on day 2 of each cycle. Primary endpoint was the duration of severe neutropenia (DSN) during Cycle 1 defined as number of consecutive days with an absolute neutrophil count (ANC) <0.5 x 109/L. The study was powered at 90% and had a hierarchical testing procedure utilizing a ±1 day margin to test for equivalence (two-sided 95% confidence interval [CI]) and then a -0.6 day non-inferiority margin (one-sided 97.5% CI) for DSN during Cycle 1. DSN was analyzed with an ANCOVA model adjusted for treatment, chemotherapy, region and baseline ANC. Secondary efficacy assessments were: time to ANC recovery, depth of ANC nadir, incidence of febrile neutropenia, number of days of fever, infection frequency and mortality due to infection. Safety and immunogenicity were assessed until 4 weeks after last study drug administration. Results: A total of 308 patients were randomized and included in the full analysis set (LA-EP2006: n=155; reference: n=153). Baseline characteristics were similar in both groups (mean±SD age: LA-EP2006 48.8±10.50, reference 49.1±10.07 years; breast cancer stage II-III: LA-EP2006 n=148 (95.5%), reference n=139 (90.8%). Mean±SD DSN in Cycle 1 was 1.36 ± 1.13 days in the LA-EP2006 group versus 1.19 ± 0.98 days in the reference group (treatment difference −0.16 days; 95% CI: −0.40, 0.08). LA-EP2006 was thus both equivalent and non-inferior to reference pegfilgrastim as the 95% CI was within the defined margin of ±1 day and the lower bound of the 95% CI was entirely above −0.6 days. There were no clinically meaningful differences between LA-EP2006 and reference in incidence of febrile neutropenia (7.7% vs 9.8% in Cycle 1, 10.3% vs 13.1% across all cycles), days with fever, depth of ANC nadir in Cycle 1, time to ANC recovery in Cycle 1, or frequency of infections. Treatment-emergent adverse events (TEAEs) were similar across groups and consistent with the known safety profile of pegfilgrastim. The most frequent TEAEs related to treatment were musculoskeletal and connective tissue disorders (LA-EP2006 16.1%, reference 13.7%). Serious TEAEs were reported in: LA-EP2006 18.7%, reference 20.9%). No neutralizing anti-pegfilgrastim antibodies were detected. Conclusions: Proposed biosimilar pegfilgrastim (LA-EP2006) met the primary endpoint demonstrating it to be both equivalent and non-inferior to the reference. LA-EP2006 and the reference are similar with no clinically meaningful differences regarding efficacy and safety in breast cancer patients receiving (neo)-adjuvant myelosuppressive chemotherapy. Acknowledgment: The authors acknowledge the other investigators who participated in the PROTECT2 study. Disclosures Blackwell: Celgene: Consultancy, Research Funding; GE Healthcare: Consultancy; Genentech: Consultancy, Research Funding; Hospira: Consultancy; Janssen: Consultancy; Novartis: Consultancy; Roche: Consultancy; Sandoz: Consultancy; Pfizer: Research Funding; Genomic Health: Speakers Bureau; Boehringer Ingelheim: Consultancy; Amgen: Consultancy. Nakov:Sandoz: Employment. Singh:Sandoz: Employment. Schaffer:Sandoz: Employment. Gascon:Sandoz: Honoraria, Speakers Bureau. Harbeck:Sandoz: Other: Chair of Data and Safety Monitoring Board (DSMB) on trials sponsored by Sandoz.

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Second interims analysis of the ARA Plus study: Breast Cancer (BC) adjuvant chemotherapy (CT) with and without darbepoetin- alpha, analysis of serious adverse events

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.564 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 564-564 ◽

Cited By ~ 2

Author(s):

K. Ziegler ◽

M. Warm ◽

C. Oberhoff ◽

T. Reimer ◽

S. Mohrmann ◽

...

Keyword(s):

Breast Cancer ◽

Febrile Neutropenia ◽

Adverse Events ◽

Protective Factor ◽

Phase Iii ◽

Breast Cancer Patients ◽

Serious Adverse Events ◽

Fatigue Syndrome ◽

Severe Infections ◽

Survival Effect

564 Background: TAC is one of the most effective regimens. It‘s associated with higher frequency of anemia and chemotherapy-induced neutropenia (CIN). The erythropoiesis stimulating factor (ESF) support of chemotherapy, its complications and survival effect remain unclear. Erythropoetins do prevent chemotherapy-associated anemia (CAA) and subsequent fatigue syndrome but their potential influence on survival is still unclear. One aim of this analysis is to investigate the correlation between CT, growth factor support and toxicity (SAE‘s). Methods: This ARA Plus phase III trial compare chemotherapy ±ARA in breast cancer patients >18 years old, with positive lymph nodes and with M0 disease. Pts get six cycles of of 5-fluoro-uracile 500mg/m2, epirubicine 100mg/m2 and cyclophosphamide 500mg/m2, (FEC, Bonneterre), 3-weekly or six cycles of docetaxcel 75mg/m2, adriamycin 50mg/m2 and cyclophosphamide 500mg/m2, (TAC, BCIRG) and are randomized to ARA 500μg q3w if Hb<13 g/dl or standard support care. Here arte the results. of SAE‘S. Results: A total of 756 pts (373 + ARA/383 -ARA) from 53 sites were enrolled since January 2004, there are 1234 pts. planned up to January 2008. 185 serious adverse events (SAE) are reported. Of these 185 SAE’s 100 (54%) had an ARA-therapy. Most frequent SAE’s were: leucopenia, febrile neutropenia, thrombosis and infections. In 9 (31%) out of the 29 febrile neuropenia SAE’s, ARA was given. 30 thromboses were reported (23+ARA/7-ARA s.) but only 10 at the verty time ARA was given. In 31 severe infections 16 (51,6%; n.s.) were reported in patients receiving ARA Therapy. From 43 patients with intestinal SAE‘s like Diarrhea/Mucositis/Nausea to 30 pts. (69,8 %) ARA eas given. Conclusions: The combination of CT and ARA is safe concerning febrile neutropenia and furthermore appears to be protective factor of this SAE when combined with TAC. There seem to be more SAE‘s concerning thrombosis and intestinal difficulties.These results allow to hypothesize that ARA therapy is associated with higher toxicity concerning thrombosis which could make the use of heparin necessary but on the other side it shows significant reduced neutropenia. No significant financial relationships to disclose.

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Randomized double-blind prospective trial to evaluate the effects of sargramostim versus placebo in a moderate-dose fluorouracil, doxorubicin, and cyclophosphamide adjuvant chemotherapy program for stage II and III breast cancer.

Journal of Clinical Oncology ◽

10.1200/jco.1996.14.11.2976 ◽

1996 ◽

Vol 14 (11) ◽

pp. 2976-2983 ◽

Cited By ~ 38

Author(s):

S E Jones ◽

M W Schottstaedt ◽

L A Duncan ◽

R L Kirby ◽

R H Good ◽

...

Keyword(s):

Breast Cancer ◽

Adjuvant Chemotherapy ◽

Dose Intensity ◽

Stage Ii ◽

Severe Neutropenia ◽

Controlled Study ◽

Moderate Dose ◽

Double Blind ◽

Long Term Outcome ◽

Gm Csf

PURPOSE To determine the effects of sargramostim (recombinant human granulocyte-macrophage colony-stimulating factor [rhu GM-CSF]) on the incidence, duration, and complications of myelosuppression after moderate-dose fluorouracil, doxorubicin, cyclophosphamide (FAC) adjuvant chemotherapy in patients with node-positive breast cancer. PATIENTS AND METHODS In this randomized, double-blind, placebo-controlled study, 142 women with stage II and III breast cancer were to receive four 21-day cycles of chemotherapy that consisted of fluorouracil 600 mg/ m2 intravenously (IV), doxorubicin 60 mg/m2 IV, and cyclophosphamide 750 mg/m2 IV on day 1, followed by placebo or GM-CSF 250 micrograms/m2/d daily subcutaneously (SC) on days 3 through 15. All patients received prophylactic ciprofloxacin by mouth when the absolute neutrophil count (ANC) was less than 1,000/microL. RESULTS Eighty-six percent of GM-CSF patients (n = 62) and 96% of placebo patients (n = 69) completed four assessable cycles of treatment on study. Overall, the median duration of severe neutropenia (ANC < 500/microL) was 2.8 days with GM-CSF and 6.8 days with placebo (P < .001); the duration of ANC less than 1,000/microL was 6.0 versus 9.1 days, respectively (P < .001). Hospitalizations for febrile neutropenia were uncommon in either group: GM-CSF, six; placebo, eight. The only other difference in hematologic toxicity was grade 3/4 thrombocytopenia observed with greater frequency in GM-CSF patients than placebo patients in cycles 3 and 4. GM-CSF increased mean the FAC dose-intensity among patients who completed two or more cycles (P < .001). GM-CSF was generally well tolerated and associated with more injection-site reactions, but less mucositis than placebo. There were no deaths on study. CONCLUSION GM-CSF significantly enhanced ANC recovery after FAC chemotherapy; it decreased the incidence and duration of associated neutropenia and moderately increased the dose-intensity of adjuvant chemotherapy. Whether these effects will ultimately translate into improved long-term outcome remains to be determined.

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