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

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 564-564 ◽  
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.

A randomized phase III study to determine the efficacy of capecitabine in addition to a taxane and bevacizumab as first-line therapy in patients with metastatic breast cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 1082-1082 ◽  
Author(s):  
Hans-Joachim Lueck ◽  
Kristina Luebbe ◽  
Joachim Bischoff ◽  
Nicolai Maass ◽  
Gabriele Feisel ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Adverse Events ◽  
Locally Advanced ◽  
Sample Size Calculation ◽  
Metastatic Breast ◽  
Phase Iii ◽  
Open Label ◽  
Serious Adverse Events ◽  
Line Therapy

1082 Background: Conventional chemotherapy combined with novel molecular targeted agents has been proven effective and tolerable in metastatic breast cancer (MBC). Taxanes (T) plus bevacizumab (B) and T plus capecitabine (X) showed a benefit in progression free survival (PFS) compared to T alone. Life-threatening or highly symptomatic situations require poly-chemotherapies in MBC patients; therefore a combination of all 3 drugs appears reasonable. Methods: TABEA (NCT01200212) is a prospective, randomized, open label, phase III trial comparing T plus B +/- X as 1st-line therapy in MBC. Patients with histologically confirmed HER2- locally advanced or MBC were included. All patients received T (paclitaxel 80 mg/m2 i.v. d1,8,15 q22 or docetaxel 75 mg/m2 i.v. d1 q22) and B (15 mg/kg i.v. d1 q22) (TB) and were randomized to X (1800 mg/m² daily d1-14 q22) in addition and concurrently to TB (TBX) or TB alone. Randomization was stratified by receptor status, planned taxane, and disease free interval (≤ or >12 months). Primary objective was PFS. Secondary objectives were response rate and duration, clinical benefit rate (CR, PR, stable disease ≥ 24 weeks), 3yr overall survival, PFS in patients ≥ 65 years, toxicity, and compliance. Sample size calculation assumed a PFS of 10 and 13.3 months for TB and TBX, respectively (HR=0.75) requiring 432 patients and 386 events with 2-sided α=0.05 and β=0.2. Interim analysis was planned after 25% of required events (n=96). Results: Planned interim futility and safety analyses after 100 documented events in 202 patients have shown no efficacy benefit and higher toxicity in the TBX arm. For PFS, HR=1.061, 95% CI (0.715, 1.576) was observed, futility boundary was crossed. Overall grade 3-4 adverse events (e.g., thrombopenia, diarrhea, hand-foot-syndrome) (72.3 vs. 57.4%, p=0.039)and serious adverse events (40.6 vs. 24.8%, p=0.016) rates were higher for TBX after 16.3 months median follow up. There were 6 deaths in the TBX vs. 1 in the TB arm. Recruitment and therapy were stopped on 5th Oct 2012 following the advice from the IDMC. Conclusions: TABEA failed to show an improvement using the 3 drug regimen TBX in high-risk MBC patients. Clinical trial information: NCT 01200212.

scholarly journals 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 ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1137 ◽  
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.

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

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e19587-e19587
Author(s):  
Igor Bondarenko ◽  
Oleg Gladkov ◽  
Reiner Elaesser ◽  
Anton Buchner ◽  
Peter Bias
Keyword(s):  
Breast Cancer ◽  
Febrile Neutropenia ◽  
Adverse Events ◽  
Stage Ii ◽  
Severe Neutropenia ◽  
Study Medication ◽  
Efficacy And Safety ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Increased Risk

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.

Comparison of Serious Adverse Events Between the Original and a Generic Docetaxel in Breast Cancer Patients

2013 ◽  
Vol 48 (4) ◽  
pp. 447-455 ◽  
Author(s):  
Éric Poirier ◽  
Christine Desbiens ◽  
Brigitte Poirier ◽  
Jean-Charles Hogue ◽  
Julie Lemieux ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adverse Events ◽  
Cancer Patients ◽  
Breast Cancer Patients ◽  
Serious Adverse Events

First and Subsequent Cycle Use of Pegfilgrastim Prevents Febrile Neutropenia in Patients With Breast Cancer: A Multicenter, Double-Blind, Placebo-Controlled Phase III Study

2005 ◽  
Vol 23 (6) ◽  
pp. 1178-1184 ◽  
Author(s):  
Charles L. Vogel ◽  
Marek Z. Wojtukiewicz ◽  
Robert R. Carroll ◽  
Sergei A. Tjulandin ◽  
Luis Javier Barajas-Figueroa ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Febrile Neutropenia ◽  
Phase Iii ◽  
Breast Cancer Patients ◽  
Open Label ◽  
Double Blind ◽  
Myelosuppressive Chemotherapy ◽  
Subsequent Cycle ◽  
Phase Iii Study ◽  
Chemotherapy Dose

Purpose We evaluated the efficacy of pegfilgrastim to reduce the incidence of febrile neutropenia associated with docetaxel in breast cancer patients. Patients and Methods Patients were randomly assigned to either placebo or pegfilgrastim 6 mg subcutaneously on day 2 of each 21-day chemotherapy cycle of 100 mg/m2 docetaxel. The primary end point was the percentage of patients developing febrile neutropenia (defined as body temperature ≥ 38.2°C and neutrophil count < 0.5 × 109/L on the same day of the fever or the day after). Secondary end points were incidence of hospitalizations associated with a diagnosis of febrile neutropenia, intravenous (IV) anti-infectives required for febrile neutropenia, and the ability to maintain planned chemotherapy dose on time. Patients with febrile neutropenia were converted to open-label pegfilgrastim in subsequent cycles. Results Nine hundred twenty-eight patients received placebo (n = 465) or pegfilgrastim (n = 463). Patients receiving pegfilgrastim, compared with patients receiving placebo, had a lower incidence of febrile neutropenia (1% v 17%, respectively; P < .001), febrile neutropenia–related hospitalization (1% v 14%, respectively; P < .001), and use of IV anti-infectives (2% v 10%, respectively; P < .001). The percentage of patients receiving the planned dose on time was similar between patients receiving pegfilgrastim and patients who initially received placebo (80% and 78%, respectively), as would be expected of the study design. Pegfilgrastim was generally well tolerated and safe, and the adverse events reported were typical of this patient population. Conclusion First and subsequent cycle use of pegfilgrastim with a moderately myelosuppressive chemotherapy regimen markedly reduced febrile neutropenia, febrile neutropenia–related hospitalizations, and IV anti-infective use.

Can adjuvant homeopathy improve the control of post-chemotherapy emesis in breast cancer patients? Results of a randomized placebo-controlled trial

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e20566-e20566
Author(s):  
I. L. Ray-Coquard ◽  
J. Provençal ◽  
A. C. Hardy-Bessard ◽  
T. Bachelot ◽  
D. Coeffic ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adverse Events ◽  
Primary Endpoint ◽  
Controlled Trial ◽  
Metastatic Breast ◽  
Nausea And Vomiting ◽  
Phase Iii ◽  
Breast Cancer Patients ◽  
Double Blind ◽  
Tac Chemotherapy

e20566 Background: Homeopathy used as an adjunct in the treatment of chemotherapy (CT)-induced emesis has rarely been evaluated. Methods: Patients with non-metastatic breast cancer treated with 6 courses of FAC 50, FEC 100 or TAC chemotherapy were randomized to Cocculus/nux vomica/tabacum/petroleum extract (Cocculine, C) or Placebo (P) in a multicentric comparative double-blind phase III study. Anti-emetic treatment was standardized (corticoids + ondansetron). Patients were evaluated after each course. The primary endpoint was nausea measured after the 1st CT course using the FLIE (Functional Living Index for Emesis) with 5-day recall. The planned sample size was 396 evaluable patients based on a minimum expected difference in mean of 0.5 ± 1.6 on a scale from 1 (a lot) to 7 (not at all) with 5% two-sided α error and 85% power. An intent-to-treat analysis was planned. Secondary evaluation criteria were: vomiting measured by the FLIE score, patient self-evaluation (EVA) and investigator recording (NCI-CTC) of nausea and vomiting intensities, and compliance. Results: From September 05 to January 08, 431 patients were randomized (217 to P and 214 to C). Patient characteristics were well balanced between groups. Median age was 53 years, 35% of the patients experienced nausea or vomiting. In total, 403 patients (93.5%) were assessable for the primary endpoint, with few nausea episodes (FLIE nausea scores after the 1st CT course were 6.02 and 6.07 for P and C, respectively) and very good compliance (81% patients complied with the protocol). Adverse events related to nausea occurred in 51% vs. 47% of the patients treated with P and C, respectively (p = 0.48). FLIE and NCI-CTC vomiting scores were similar between the 2 arms (6.91 vs. 6.88, p = 0.47, and 20% vs. 21%, p = 0.73, for P and C, respectively). Grade II-III nausea occurred in 17.6% and 15.7% of patients receiving P and C (p = 0.62). Conclusions: No benefit of homeopathy over standard treatment was noted in this study. But surprisingly we observed lower rates of nausea and vomiting measured by patients and by investigators, than in other studies using identical chemotherapy regimens. The observation and management of emesis could modify the perception and rate of such adverse events. No significant financial relationships to disclose.

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

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 9125-9125 ◽  
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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