Hexafil: Individualized or guideline-concordant G-CSF usage—Is there a bridge?

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e20563-e20563
Author(s):  
Hans Tesch ◽  
DeLi Tilly Chang ◽  
Bertram Ottillinger
Keyword(s):  
Cancer Patients ◽  
Interim Analysis ◽  
Treatment Duration ◽  
Secondary Prophylaxis ◽  
Breast Cancer Patients ◽  
Exclusion Criteria ◽  
The Impact ◽  
Insight Into ◽  
Biosimilar Filgrastim ◽  
Clinical Trial Information

e20563 Background: G-CSF is frequently used to prevent/treat chemotherapy (CT)-induced neutropenia (CIN) in cancer patients. The non-interventional observational study HEXAFIL on the use of biosimilar filgrastim (EP-2006) was conducted to provide further insight into G-CSF usage with respect to guidelines (EORTC, ASCO) in Germany. Methods: Patients who signed informed consents were enrolled. Data were documented for up to 3 consecutive G-CSF-supported CT-cycles. Rates of modified CT-treatments (dose modification/discontinuation of drug) were calculated by the number and percentage of patients affected; data presented are based on the first CT-cycle. In/Exclusion criteria: www.germanctr.de . Results: A total of 709 breast cancer patients were included in this interim analysis (9/2012). Only 2.0% of all patients experienced febrile neutropenia (FN) and 8.7% neutropenic complications. A majority of patients received primary (49.4%, PP) or secondary prophylaxis (33.6%, SP) with the biosimilar G-CSF. However, 17.1% were treated interventional (TX). Median G-CSF treatment duration was 4d with median start on day 6 after CT. Of all documented patients, 96.3% received CT without modifications; in 3.0% of the patients dose of CT was modified and in 0.8% CT drug was discontinued. To investigate potential effects of guideline-concordant G-CSF treatment the following populations were selected: patients with FN-risk > 20% and (1) G-CSF initiation < day 5 after CT (ie, “guideline-concordant” GL; N=104) or (2) G-CSF initiation starting > day 6 after CT (ie, “individualized” IND; N=169). As expected, IND-patients experienced FN twice as often as GL-patients (4.1% vs 1.9%). Moreover, CT treatment had to be modified in 6.5% of IND-patients compared with only 1.0% of GL-patients. Conclusions: A total of 96.3% of all analyzed patients receiving biosimilar G-CSF-supported CT-cycles had no modification to their CT-regimen. Data indicate that IND-patients showed a higher rate of CT disturbances/FNs and, as a consequence, should “cross the bridge” to potentially benefit from guideline-concordant treatment. However, further data are required to detail the impact of individualized G-CSF treatment. Clinical trial information: DRKS00000313.

Non-Interventional Study Hexafil: G-CSF Use in Accordance to Guidelines?

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2057-2057 ◽  
Author(s):  
Hans Tesch ◽  
Wolfgang Abenhardt ◽  
Lutz Dietze ◽  
DeLi Tilly Chang ◽  
Bertram Ottillinger
Keyword(s):  
Cancer Patients ◽  
Secondary Prophylaxis ◽  
Published Data ◽  
Interventional Study ◽  
Self Assessment ◽  
Exclusion Criteria ◽  
Antineoplastic Treatment ◽  
Prophylactic Use ◽  
Insight Into ◽  
Biosimilar Filgrastim

Abstract Abstract 2057 Purpose of the study: Chemotherapy (CT) induced neutropenia (CIN) is a common complication in the treatment of cancer and often leads to modifications of antineoplastic treatment. Granulocyte-colony stimulating factors (G-CSF) are frequently used to prevent or treat CIN in cancer patients. The non-interventional observational study HEXAFIL on the use of biosimilar filgrastim (EP-2006) was conducted to provide further insight into its therapeutic efficacy and routine clinical use in Germany, especially in compliance with guidelines on the use of G-CSF (EORTC, ASCO). Methods: 1460 patients who signed informed consents are to be enrolled at 100 German sites. Data is documented for up to 3 consecutive filgrastim-supported CT-cycles. Rates of modified CT-treatments (dose modification/discontinuation of drug) are calculated by the number and percentage of patients affected; data presented are based on the first CT-cycle. Inclusion/Exclusion criteria: www.germanctr.de. Results: By 7/2012, data of 955 patients were available. Patients' mean age was 59 years (19 to 89), 75% of them being female. Most common tumour entities were breast cancer (57.2%), NHL (10.7%), lung cancer (7.6%), ovarian cancer (4.0%) and Hodgkin lymphoma (3.1%). Substances most commonly used for chemotherapy were cyclophosphamide (50.7%), epirubicin (33.2%), docetaxel (23.6%), 5-fluorouracil (20.9%) and doxorubicin (15.6%). In line with published data only 1.9% of all patients experienced febrile neutropenia (FN), 8.7% neutropenic complications and 14% had leukopenia CTC 4 at nadir. As expected and according to guidelines the majority of patients received primary (39.3%, PP) or secondary prophylaxis (32.9%, SP) with biosimilar filgrastim, however, 25.8% were treated on demand (TX, i.e. after having experienced neutropenic complications in the first documented CT cycle or a drop in leukocytes putting the patient at acute risk of neutropenic complications). Interestingly, if viewed by the presence of baseline leukopenia, 76.9% of all patients without leukopenia (CTC 0) received G-CSF prophylaxis (PP/SP) but only 46.1% of all patients with leukopenia CTC 3/4. In patients without baseline leukopenia receiving filgrastim for PP, leukopenia CTC 3/4 at nadir was present in 32.9%, whereas in SP it was 50.6% and in TX 70.8%. Median filgrastim treatment duration was 4 d (1 to 14). Patients with PP received median 5 days of treatment starting on median day 6 after CT, whereas SP and TX patients were treated on median day 8 and 9, respectively, for a median duration of 3 days each. Accordingly, patients with neutropenic complications received treatment starting on median day 8 for 3 days (median), whereas patients without neutropenic complications started on median day 7 for 5 days (median); moreover, patients with FN only started biosimilar filgrastim therapy on median day 9. 93.9% of all documented patients received CT without any modification; in 4.6% of patients the dose of chemotherapy was modified and in 1.4% a chemotherapy drug was discontinued. Data indicate that patients with earlier and longer filgrastim treatment showed less chemotherapy disturbances, FN and neutropenic complications. Conclusions: Approximately 94% of all documented patients received filgrastim-supported CT-cycles without any modification of the CT-regimen. Yet, there is still room for improvement in prevention of CIN/FN in cancer patients as reflected by median start/treatment days and number of neutropenic complications. Moreover, daily injections should not impact the prophylactic use of G-CSF as revealed by self-assessment questionnaires in which patients reported handling of the needle guard system and of the pre-filled syringes to be easy or very easy (97.7% and 97.8%, respectively and calculated on questionnaires evaluable). Disclosures: Tesch: Amgen, Astra Zeneca, Boehring Ingelheim, Celgene, GSK, Hexal, Janssen Cilag, Lilly, Merck, Novartis, Pfizer, Roche: Honoraria; Amgen, Astra Zeneca, Boehring Ingelheim, Celgene, GSK, Hexal, Janssen Cilag, Lilly, Merck, Novartis, Pfizer, Roche; Sanofi Aventis: Consultancy. Abenhardt:Hexal: Honoraria. Dietze:Hexal: Honoraria. Chang:Hexal: Employment. Ottillinger:Hexal, Sandoz: Consultancy, Honoraria.

scholarly journals CBR3 V244M is associated with LVEF reduction in breast cancer patients treated with doxorubicin

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Jennifer K. Lang ◽  
Badri Karthikeyan ◽  
Adolfo Quiñones-Lombraña ◽  
Rachael Hageman Blair ◽  
Amy P. Early ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Care Center ◽  
Left Ventricular ◽  
The Body ◽  
Left Ventricular Ejection ◽  
Breast Cancer Patients ◽  
Ventricular Ejection Fraction ◽  
Echocardiographic Parameters ◽  
The Impact

Abstract Background The CBR3 V244M single nucleotide polymorphism has been linked to the risk of anthracycline-related cardiomyopathy in survivors of childhood cancer. There have been limited prospective studies examining the impact of CBR3 V244M on the risk for anthracycline-related cardiotoxicity in adult cohorts. Objectives This study evaluated the presence of associations between CBR3 V244M genotype status and changes in echocardiographic parameters in breast cancer patients undergoing doxorubicin treatment. Methods We recruited 155 patients with breast cancer receiving treatment with doxorubicin (DOX) at Roswell Park Comprehensive Care Center (Buffalo, NY) to a prospective single arm observational pharmacogenetic study. Patients were genotyped for the CBR3 V244M variant. 92 patients received an echocardiogram at baseline (t0 month) and at 6 months (t6 months) of follow up after DOX treatment. Apical two-chamber and four-chamber echocardiographic images were used to calculate volumes and left ventricular ejection fraction (LVEF) using Simpson’s biplane rule by investigators blinded to all patient data. Volumetric indices were evaluated by normalizing the cardiac volumes to the body surface area (BSA). Results Breast cancer patients with CBR3 GG and AG genotypes both experienced a statistically significant reduction in LVEF at 6 months following initiation of DOX treatment for breast cancer compared with their pre-DOX baseline study. Patients homozygous for the CBR3 V244M G allele (CBR3 V244) exhibited a further statistically significant decrease in LVEF at 6 months following DOX therapy in comparison with patients with heterozygous AG genotype. We found no differences in age, pre-existing cardiac diseases associated with myocardial injury, cumulative DOX dose, or concurrent use of cardioprotective medication between CBR3 genotype groups. Conclusions CBR3 V244M genotype status is associated with changes in echocardiographic parameters suggestive of early anthracycline-related cardiomyopathy in subjects undergoing chemotherapy for breast cancer.

scholarly journals PITX2 DNA-Methylation: Predictive versus Prognostic Value for Anthracycline-Based Chemotherapy in Triple-Negative Breast Cancer Patients

Breast Care ◽  
2020 ◽  
pp. 1-9
Author(s):  
Rudolf Napieralski ◽  
Gabriele Schricker ◽  
Gert Auer ◽  
Michaela Aubele ◽  
Jonathan Perkins ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Methylation ◽  
Cancer Patients ◽  
Triple Negative Breast Cancer ◽  
Predictive Value ◽  
Untreated Patient ◽  
Triple Negative ◽  
Statistical Significance ◽  
Breast Cancer Patients ◽  
The Impact

<b><i>Background:</i></b> PITX2 DNA methylation has been shown to predict outcomes in high-risk breast cancer patients after anthracycline-based chemotherapy. To determine its prognostic versus predictive value, the impact of PITX2 DNA methylation on outcomes was studied in an untreated cohort vs. an anthracycline-treated triple-negative breast cancer (TNBC) cohort. <b><i>Material and Methods:</i></b> The percent DNA methylation ratio (PMR) of paired-like homeodomain transcription factor 2 (PITX2) was determined by a validated methylation-specific real-time PCR test. Patient samples of routinely collected archived formalin-fixed paraffin-embedded (FFPE) tissue and clinical data from 144 TNBC patients of 2 independent cohorts (i.e., 66 untreated patients and 78 patients treated with anthracycline-based chemotherapy) were analyzed. <b><i>Results:</i></b> The risk of 5- and 10-year overall survival (OS) increased continuously with rising PITX2 DNA methylation in the anthracycline-treated population, but it increased only slightly during 10-year follow-up time in the untreated patient population. PITX2 DNA methylation with a PMR cutoff of 2 did not show significance for poor vs. good outcomes (OS) in the untreated patient cohort (HR = 1.55; <i>p</i> = 0.259). In contrast, the PITX2 PMR cutoff of 2 identified patients with poor (PMR &#x3e;2) vs. good (PMR ≤2) outcomes (OS) with statistical significance in the anthracycline-treated cohort (HR = 3.96; <i>p</i> = 0.011). The results in the subgroup of patients who did receive anthracyclines only (no taxanes) confirmed this finding (HR = 5.71; <i>p</i> = 0.014). <b><i>Conclusion:</i></b> In this hypothesis-generating study PITX2 DNA methylation demonstrated predominantly predictive value in anthracycline treatment in TNBC patients. The risk of poor outcome (OS) correlates with increasing PITX2 DNA methylation.

scholarly journals Surgery for primary tumor benefits survival for breast cancer patients with bone metastases: a large cohort retrospective study

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Zhangheng Huang ◽  
Xin Zhou ◽  
Yuexin Tong ◽  
Lujian Zhu ◽  
Ruhan Zhao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prognostic Factors ◽  
Bone Metastases ◽  
Cancer Patients ◽  
Primary Tumor ◽  
Predictive Accuracy ◽  
Rank Test ◽  
Breast Cancer Patients ◽  
Risk Of Death ◽  
The Impact

Abstract Background The role of surgery for the primary tumor in breast cancer patients with bone metastases (BM) remains unclear. The purpose of this study was to determine the impact of surgery for the primary tumor in breast cancer patients with BM and to develop prognostic nomograms to predict the overall survival (OS) of breast cancer patients with BM. Methods A total of 3956 breast cancer patients with BM from the Surveillance, Epidemiology, and End Results database between 2010 and 2016 were included. Propensity score matching (PSM) was used to eliminate the bias between the surgery and non-surgery groups. The Kaplan-Meier analysis and the log-rank test were performed to compare the OS between two groups. Cox proportional risk regression models were used to identify independent prognostic factors. Two nomograms were constructed for predicting the OS of patients in the surgery and non-surgery groups, respectively. In addition, calibration curve, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA) were used to evaluate the performance of nomograms. Result The survival analysis showed that the surgery of the primary tumor significantly improved the OS for breast cancer patients with BM. Based on independent prognostic factors, separate nomograms were constructed for the surgery and non-surgery groups. The calibration and ROC curves of these nomograms indicated that both two models have high predictive accuracy, with the area under the curve values ≥0.700 on both the training and validation cohorts. Moreover, DCA showed that nomograms have strong clinical utility. Based on the results of the X-tile analysis, all patients were classified in the low-risk-of-death subgroup had a better prognosis. Conclusion The surgery of the primary tumor may provide survival benefits for breast cancer patients with BM. Furthermore, these prognostic nomograms we constructed may be used as a tool to accurately assess the long-term prognosis of patients and help clinicians to develop individualized treatment strategies.

scholarly journals Trastuzumab Mechanism of Action; 20 Years of Research to Unravel a Dilemma

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3540
Author(s):  
Hamid Maadi ◽  
Mohammad Hasan Soheilifar ◽  
Won-Shik Choi ◽  
Abdolvahab Moshtaghian ◽  
Zhixiang Wang
Keyword(s):  
Breast Cancer ◽  
Targeted Therapy ◽  
Cancer Patients ◽  
Mechanism Of Action ◽  
Mechanisms Of Action ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Insight Into ◽  
Positive Breast Cancer

Trastuzumab as a first HER2-targeted therapy for the treatment of HER2-positive breast cancer patients was introduced in 1998. Although trastuzumab has opened a new avenue to treat patients with HER2-positive breast cancer and other types of cancer, some patients are not responsive or become resistant to this treatment. So far, several mechanisms have been suggested for the mode of action of trastuzumab; however, the findings regarding these mechanisms are controversial. In this review, we aimed to provide a detailed insight into the various mechanisms of action of trastuzumab.

P237 The impact of body composition change on neo-adjuvant chemotherapy for breast cancer patients

The Breast ◽  
2015 ◽  
Vol 24 ◽  
pp. S106-S107
Author(s):  
T. Iwase ◽  
T. Sangai ◽  
E. Ishigami ◽  
J. Sakakibara ◽  
K. Fujisaki ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Body Composition ◽  
Adjuvant Chemotherapy ◽  
Cancer Patients ◽  
Composition Change ◽  
Breast Cancer Patients ◽  
Body Composition Change ◽  
Neo Adjuvant Chemotherapy ◽  
The Impact

Impact of adding plinabulin to pegfilgrastim for the prevention of TAC chemotherapy (Chemo) induced neutropenia (CIN), on patient quality of life (QoL).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e24031-e24031
Author(s):  
Ramon Mohanlal ◽  
Yvette Lelorier ◽  
Dominic Mitchell ◽  
Lan Huang ◽  
Douglas W. Blayney
Keyword(s):  
Clinical Trial ◽  
Energy Levels ◽  
Breast Cancer Patients ◽  
Emotional Wellbeing ◽  
Phase 3 ◽  
Tac Chemotherapy ◽  
Physical Wellbeing ◽  
The Impact ◽  
Clinical Trial Information

e24031 Background: Plinabulin is a novel non-G-CSF small molecule being developed for the prevention of chemotherapy in conjunction with pegfilgrastim and is administered via 30 min IV infusion, 30 min after chemo on Day (D) 1. The QoL was analyzed using the Functional Assessment of Cancer Therapy - General questionnaire (FACT-G) as part of a phase 3 (Ph3) clinical trial comparing pegfilgrastim alone versus pegfilgrastim and plinabulin for the prevention of neutropenia in newly diagnosed breast cancer patients being treated with Docetaxel (75 mg/m2), Doxorubicin (50 mg/m2), and Cyclophosphamide (500 mg/m2) (TAC) on D1 for four 21 D cycles and study treatment. Methods: The FACT-G was administered to patients in China and Ukraine using an ePRO app downloaded onto patients' phones as part of the Phase 3 PROTECTIVE-2 trial (NCT0329457) with TAC. Patients completed the FACT-G during each chemo cycle at D-1, D1, D8 and D15. Patients received reminders 1 hour before the required completion time and all entries were time stamped. The FACT-G measured the impact of cancer on four categories: Physical wellbeing, Social wellbeing, Emotional wellbeing and Functional wellbeing. Results: Compared to pegfilgrastim alone, patients on plinabulin + pegfilgrastim performed significantly better for Physical wellbeing on D8 and D15 of Cycle 2 (p < 0.0589 and p < 0.0039 respectively) and Cycle 3 (p < 0.0360 and p < 0.0343 respectively). Further analysis of the sub questions showed that both energy levels “I have a lack of energy” and pain”(I have pain” were significantly better for the plinabulin + pegfilgrastim combination versus pegfilgrastim alone (p < 0.0377 and p < 0.0420 respectively). Overall FACT-G completion compliance for the trial was 91%. Conclusions: The Physical wellbeing (in particular, pain and for energy levels) of patients receiving plinabulin in combination with pegfilgrastim for the prevention of TAC CIN, was significantly less impacted by chemo dosing compared to the pegfilgrastim alone arm. In addition, the results suggest that patients receiving the combination therapy recovered their pre-chemo Physical wellbeing levels more rapidly. Clinical trial information: NCT03531099.

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