scholarly journals High-Dose Chemotherapy for Breast Cancer: The French PEGASE Experience

2003 ◽  
Vol 10 (1) ◽  
pp. 42-47 ◽  
Author(s):  
Henri Rochéa ◽  
Patrice Viens ◽  
Pierre Biron ◽  
Jean-Pierre Lotz ◽  
Bernard Asselain
Keyword(s):  
Breast Cancer ◽  
Adjuvant Therapy ◽  
Disease Free Survival ◽  
High Dose Chemotherapy ◽  
Phase Iii ◽  
High Dose ◽  
Free Survival ◽  
Disease Free ◽  
Ongoing Phase ◽  
Risk Breast Cancer

Background Early studies of high-dose chemotherapy (HDC) for breast cancer were limited by small numbers and the lack of adequate control groups. The French PEGASE Group was founded to perform larger and properly randomized comparative studies of this approach. Methods The program was created to determine the effects of intensive chemotherapy for breast cancer. The seven PEGASE protocols addressed HDC as adjuvant therapy (01 and 06) and as treatment for inflammatory nonmetastatic disease (02, 05, and 07) and metastatic disease (03 and 04). Two of these protocols are ongoing. Results The PEGASE 01 adjuvant therapy trial showed that 3-year disease-free survival was significantly better in the HDC arm but overall survival was unchanged. The ongoing phase III 06 trial is studying a higher dosage regimen. The HDC trials for metastatic and inflammatory nonmetastatic disease are encouraging. Conclusions Many clinicians no longer subscribe to the concept of HDC for breast cancer. Overall outcomes from management of poor-risk breast cancer remain poor, however, and it is possible that some selected subgroups of patients may benefit from such an approach.

Invasive disease-free survival benefit following neratinib as extended adjuvant therapy in centrally-confirmed HER2+ early-stage breast cancer: The ExteNET phase III randomized placebo-controlled trial.

2015 ◽  
Vol 33 (28_suppl) ◽  
pp. 117-117 ◽  
Author(s):  
Arlene Chan ◽  
Miguel Martin ◽  
Gunter Von Minckwitz ◽  
Bent Ejlertsen ◽  
Stephen K. L. Chia ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Therapy ◽  
Ductal Carcinoma ◽  
Early Stage ◽  
Disease Free Survival ◽  
Metastatic Breast ◽  
Invasive Disease ◽  
Phase Iii ◽  
Free Survival ◽  
Disease Free

117 Background: Neratinib is an irreversible pan-HER tyrosine kinase inhibitor with clinical efficacy in trastuzumab pre-treated HER2-positive (HER2+) metastatic breast cancer (BC). ExteNET is an ongoing multicenter randomized placebo-controlled phase III trial evaluating the efficacy and safety of a 1-year course of neratinib in patients with early-stage HER2+ BC after trastuzumab-based adjuvant therapy (clinicaltrials.gov: NCT00878709). Methods: Women with locally-confirmed early-stage HER2+ BC were randomly assigned to oral neratinib 240mg/day or matching placebo for 1 year. Archived diagnostic tumor samples were submitted for HER2 gene amplification testing at a central laboratory. Primary endpoint: invasive disease-free survival (iDFS). Secondary endpoints: DFS including ductal carcinoma in situ (DFS+DCIS); distant disease-free survival (DDFS); time to distant recurrence (TDR). Stratified Cox proportional-hazards models were used to estimate hazard ratios (HR) for the ITT and amended ITT (aITT) populations; unstratified models were used for the centrally confirmed HER2 population. Treatment groups were compared using 2-sided log-rank tests. Results: The ITT population included 2840 patients (neratinib, N=1420; placebo, N=1420). The higher-risk aITT population (i.e. node-positive disease and randomized ≤1 year of completing prior trastuzumab) included 1873 patients (neratinib, N=938; placebo, N=935). Of the tumor samples analyzed, 1463 (86%) were centrally confirmed (neratinib, N=741; placebo, N=722). Conclusions: Neratinib significantly improves iDFS in trastuzumab-treated early-stage HER2+ BC patients. An enhanced treatment effect is observed with neratinib in women with centrally confirmed HER2+ tumors. Clinical trial information: NCT00878709. [Table: see text]

Impact of uncertainty on cost-effectiveness analysis of medical strategies: The case of high-dose chemotherapy for breast cancer patients

2005 ◽  
Vol 21 (3) ◽  
pp. 342-350 ◽  
Author(s):  
Patricia Marino ◽  
Carole Siani ◽  
Henri Roché ◽  
Jean-Paul Moatti ◽  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Cost Effectiveness ◽  
Cancer Patients ◽  
Disease Free Survival ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Breast Cancer Patients ◽  
Free Survival ◽  
Disease Free

Objectives: The object of this study was to determine, taking into account uncertainty on cost and outcome parameters, the cost-effectiveness of high-dose chemotherapy (HDC) compared with conventional chemotherapy for advanced breast cancer patients.Methods: An analysis was conducted for 300 patients included in a randomized clinical trial designed to evaluate the benefits, in terms of disease-free survival and overall survival, of adding a single course of HDC to a four-cycle conventional-dose chemotherapy for breast cancer patients with axillary lymph node invasion. Costs were estimated from a detailed observation of physical quantities consumed, and the Kaplan–Meier method was used to evaluate mean survival times. Incremental cost-effectiveness ratios were evaluated successively considering disease-free survival and overall survival outcomes. Handling of uncertainty consisted in construction of confidence intervals for these ratios, using the truncated Fieller method.Results: The cost per disease-free life year gained was evaluated at 13,074€, a value that seems to be acceptable to society. However, handling uncertainty shows that the upper bound of the confidence interval is around 38,000€, which is nearly three times higher. Moreover, as no difference was demonstrated in overall survival between treatments, cost-effectiveness analysis, that is a cost minimization, indicated that the intensive treatment is a dominated strategy involving an extra cost of 7,400€, for no added benefit.Conclusions: Adding a single course of HDC led to a clinical benefit in terms of disease-free survival for an additional cost that seems to be acceptable, considering the point estimate of the ratio. However, handling uncertainty indicates a maximum ratio for which conclusions have to be discussed.

High-Dose Chemotherapy in the Adjuvant Treatment of Breast Cancer: Benefit/Risk Analysis

1998 ◽  
Vol 5 (5) ◽  
pp. 394-405 ◽  
Author(s):  
Benjamin Djulbegovic ◽  
Iztok Hozo ◽  
Karen K. Fields ◽  
Daniel Sullivan
Keyword(s):  
Breast Cancer ◽  
Disease Free Survival ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Efficacy Rate ◽  
Breast Cancer Patients ◽  
Free Survival ◽  
High Risk Breast Cancer ◽  
High Risk Breast ◽  
Risk Breast Cancer

Backgroundg High-dose chemotherapy (HDRx) may improve the prognosis of patients with high-risk breast cancer but at the expense of increased toxicity. However, no randomized, controlled trials have been published that clearly demonstrate the superiority of HDRx over conventional adjuvant chemotherapy. Methods We developed a simple model to compare benefits and risks of HDRx with conventional adjuvant chemotherapy (SDRx). The model integrates data on efficacy and risks of two competing treatment strategies into a single decision rule. Results and Conclusions Using data from phase II studies, we show that if a disease-free survival is considered to be the most important outcome, HDRx should be administered when the probability of breast cancer relapse at five years exceeds 54% to 71% for patients with 4 to 9 positive nodes and exceeds 29% to 40% for patients with >9 positive nodes. If the endpoint of interest is five-year overall survival, then the treatment should be administered when the probability of relapse exceeds 77% to 83% for patients with 4 to 9 nodes involved and 22% to 31% for those with >9 lymph nodes involved. While awaiting results of randomized, controlled trials to definitively establish the efficacy rate of HDRx, we also found that HDRx could be considered in the management of high-risk breast cancer if its efficacy rate is at least 54% to 60% superior to SDRx in reducing relapse risk in breast cancer patients with 4 to 9 nodes and at least 31% to 38% for >9 positive nodes. If survival data are used instead of disease-free survival outcomes, HDRx efficacy should be at least 47% to 48% superior to SDRx in reducing death risk in breast cancer patients with 4 to 9 nodes and at least 27% to 30% superior for >9 positive nodes to consider its use in the adjuvant setting.

High-dose chemotherapy for relapsed and refractory diffuse large B-cell lymphoma: mediastinal localization predicts for a favorable outcome.

1998 ◽  
Vol 16 (1) ◽  
pp. 63-69 ◽  
Author(s):  
U Popat ◽  
D Przepiork ◽  
R Champlin ◽  
W Pugh ◽  
K Amin ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Disease Free Survival ◽  
Large Cell ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Free Survival ◽  
Ann Arbor ◽  
Large Cell Lymphoma ◽  
Disease Free

PURPOSE This study was performed to evaluate the outcome of high-dose chemotherapy and autologous transplantation in patients with diffuse B-cell large-cell lymphoma, and, specifically, to evaluate the impact of primary mediastinal localization on the outcome of high-dose chemotherapy. PATIENTS AND METHODS A retrospective review was performed of all patients with diffuse large B-cell lymphoma who underwent autologous marrow or peripheral-blood stem-cell transplantation at our institution between January 1 986 and December 1995. RESULTS Ninety patients were identified, of whom 31 (34%) had a primary mediastinal B-cell large-cell lymphoma (PML). Cumulative probabilities of disease-free survival, overall survival, and disease progression are 40% (95% confidence interval [CI], 29 to 51), 42% (95% CI, 31 to 53), and 52% (95% CI, 40 to 64), respectively. By univariate analysis, low lactate dehydrogenase (LDH) level and low Ann Arbor stage at transplant were associated with improved survival and disease-free survival. There was a trend for improved disease-free survival and survival for patients with PML. Multivariate stepwise Cox regression analysis showed that LDH level, Ann Arbor stage, and primary mediastinal localization were independent favorable prognostic factors for disease-free survival and survival. LDH level and Ann Arbor stage were also predictive for the risk of disease progression. CONCLUSION Our results indicate that patients with PML may display an increased susceptibility to high-dose chemotherapy compared with other types of B-cell large-cell lymphoma. These findings, if confirmed, may have implications for the initial management of patients with PML.

scholarly journals Rationale and description of a lifestyle intervention programme to achieve moderate weight loss in women with non-metastatic breast cancer: the lifestyle intervention part of the SUCCESS C Study

2020 ◽  
pp. bmjnph-2020-000119
Author(s):  
Dagmar Hauner ◽  
Brigitte Rack ◽  
Thomas Friedl ◽  
Philip Hepp ◽  
Wolfgang Janni ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Weight Loss ◽  
Lifestyle Intervention ◽  
Disease Free Survival ◽  
Metastatic Breast ◽  
Phase Iii ◽  
Intervention Programme ◽  
Long Term Outcome ◽  
Free Survival ◽  
Disease Free

ObjectiveThere is growing evidence from observational studies that lifestyle factors such as obesity, an unhealthy diet and lack of physical activity are associated with poor long-term outcome in women with breast cancer. The primary objective of the lifestyle modification part of the Simultaneous Study of Docetaxel Based Anthracycline Free Adjuvant Treatment Evaluation, as well as Life Style Intervention Strategies (SUCCESS C) Trial is to investigate the effect of an individualised lifestyle intervention programme aiming at moderate weight loss on disease-free survival in women with HER2/neu-negative breast cancer. Secondary objectives include the effect of the intervention on body weight, cardiovascular risk and quality of life.MethodsThe SUCCESS C Trial is an open-label, multicentre, randomised controlled phase III study using a 2×2 factorial design in women with newly diagnosed HER2/neu-negative intermediate-risk to high-risk breast cancer. The first randomisation served to compare disease-free survival in patients treated with two different chemotherapy regimens (3642 participants). The second randomisation served to compare disease-free survival in patients with a body mass index of 24–40 kg/m² (2292 participants) receiving either a telephone-based individualised lifestyle intervention programme for moderate weight loss or general recommendations for a healthy lifestyle for 2 years. Outcome analyses will be conducted after 5 years of follow-up.PerspectiveThis study will provide information on the efficacy and safety of a comprehensive lifestyle intervention programme on disease-free survival in a large cohort of women with breast cancer. EU Clinical Trials Identifier: 2008-005453-38.

Intensification of Adjuvant Chemotherapy: 5-Year Results of a Randomized Trial Comparing Conventional Doxorubicin and Cyclophosphamide With High-Dose Mitoxantrone and Cyclophosphamide With Filgrastim in Operable Breast Cancer With 10 or More Involved Axillary Nodes

2001 ◽  
Vol 19 (3) ◽  
pp. 612-620 ◽  
Author(s):  
Pierre Fumoleau ◽  
Franck Chauvin ◽  
Moïse Namer ◽  
Roland Bugat ◽  
Michèle Tubiana-Hulin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Chemotherapy ◽  
Randomized Trial ◽  
Disease Free Survival ◽  
Dose Intensity ◽  
High Dose ◽  
Free Survival ◽  
Axillary Nodes ◽  
Significant Difference ◽  
Disease Free

PURPOSE: To determine whether intensifying the dose of adjuvant chemotherapy improves the outcome of women with primary breast cancer and 10 or more involved axillary nodes. PATIENTS AND METHODS: Patients (n = 150) were randomized to receive either four cycles of standard doxorubicin 60 mg/m2 plus cyclophosphamide 600 mg/m2 every 3 weeks (arm A) or four courses of intensified mitoxantrone 23 mg/m2 plus cyclophosphamide 600 mg/m2, with filgrastim 5 g/kg/d from days 2 to 15, every 3 weeks (arm B). Disease-free survival (DFS), distant disease-free survival (DDFS), and overall survival (OS) were determined using life-table estimates. RESULTS: There were no significant differences in DFS (P = .44), DDFS (P = .67), or OS (P = .99) between the two groups at 5 years; DDFS was 45% (arm A) versus 50% (arm B), and DFS was 41% versus 49%, respectively. Five-year survival was similar in both arms (61% v 60%, respectively). Failure to note an intergroup difference in outcome was unrelated to relative dose-intensity. Analysis of patients with 15 or more positive nodes revealed a significant difference in 5-year DDFS (19% v 49% in arm B; P = .01). Toxicity was generally mild in both groups, with no toxic death. The incidence of febrile neutropenia was low (0.3% v 3%). Alopecia was less frequent in arm B (P < .001). CONCLUSION: This randomized trial confirms the feasibility of administering mitoxantrone 23 mg/m2 with cyclophosphamide and filgrastim. Although there was no significant difference between conventional and intensified arms at 5 years, according to subgroup analysis, intensified treatment may decrease the risk of relapse in patients with 15 or more positive nodes compared with doxorubicin an cyclophosphamide.

scholarly journals Adding pertuzumab to adjuvant therapy for high-risk HER2-positive early breast cancer in APHINITY: a GRADE analysis

2020 ◽  
Vol 9 (6) ◽  
pp. 423-430 ◽  
Author(s):  
Alberto Zambelli ◽  
Giovanni Pappagallo ◽  
Paolo Marchetti
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Adjuvant Therapy ◽  
Early Breast Cancer ◽  
Disease Free Survival ◽  
Invasive Disease ◽  
Her2 Positive ◽  
Free Survival ◽  
Distant Relapse ◽  
Disease Free

Aim: Adding pertuzumab to standard trastuzumab-based adjuvant therapy significantly improved invasive disease-free survival (IDFS) in the APHINITY trial. However, the magnitude of benefit was marginal in the overall population. Methods: We used GRADE (Grading of Recommendations Assessment, Development and Evaluation) analysis on data from APHINITY to build summary-of-findings tables to evaluate the efficacy, safety and quality of evidence of predefined clinical outcomes for the addition of pertuzumab to trastuzumab-based adjuvant therapy in patients with high-risk HER2-positive early breast cancer. Results: Pertuzumab significantly improved 3-year, event-free, absolute benefit in disease-free survival, IDFS and distant relapse-free interval (DFRI) in patients with node-positive or hormone receptor-negative disease. The analysis provides strength of evidence supporting the addition of pertuzumab in this patient population.

scholarly journals A disintegrin and metalloprotease 23 hypermethylation predicts decreased disease‐free survival in low‐risk breast cancer patients

2019 ◽  
Vol 110 (5) ◽  
pp. 1695-1704 ◽  
Author(s):  
Iveta Zmetakova ◽  
Lenka Kalinkova ◽  
Bozena Smolkova ◽  
Viera Horvathova Kajabova ◽  
Zuzana Cierna ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Disease Free Survival ◽  
Low Risk ◽  
Breast Cancer Patients ◽  
Free Survival ◽  
Disease Free ◽  
Risk Breast Cancer

Assessment of efficacy of trastuzumab (Herceptin) comprising adjuvant therapy of HER2+ breast cancer patients determined based upon statistical analysis of overall survival (OS) and disease-free survival (PFS)

2018 ◽  
Vol 6 (1) ◽  
Author(s):  
Beata Jagielska ◽  
Andrzej Czubek ◽  
Konrad Tałasiewicz ◽  
A. Twarowski ◽  
P. Rutkowski ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Statistical Analysis ◽  
Adjuvant Therapy ◽  
Disease Free Survival ◽  
Clinical Staging ◽  
Primary Tumors ◽  
Free Survival ◽  
Adjuvant Immunotherapy ◽  
Disease Free

Introduction In patients suffering from breast cancer, adjuvant radiation, chemotherapy, or immunotherapy, which immediately follow the surgery as the first line therapy, greatly improve overall (OS) and disease-free survival (DFS). Various regimens of adjuvant therapy for these patients have been tested contingent upon the clinical staging. Inclusion of adjuvant immunotherapy is particularly promising. Specific aim The aim of this study was to assess efficacy of trastuzumab (Herceptin) - comprising adjuvant immunotherapy in terms of overall and disease-free survival as compared to other adjuvant therapies. Patients All patients were presented with the Patient Bill of Rights and have provided the Patient Informed Consent to participate in this study. Eligible patients include those with primary tumors initially staged at the clinical stages: I-T1c N0, II-T0-2, N0-1, or IIIA-T3 N1, or patients for whom neoadjuvant chemotherapy provides the possibility to remove surgically a tumor at the stage IIIA T0-3 N2. Of 9,058 patients enrolled in the Breast Cancer Treatment Program between 2008 and 2015, 6,832 fulfilled the inclusion criteria. Statistical Analysis The effects of clinical and demographic factors on overall survival (OS) and disease-free survival (DFS) were assessed using Cox’s proportional hazards regression models. OS and DFS were evaluated with Kaplan-Meier calculations. The study was meeting the criteria for a controlled, open-access clinical trial. Results OS rates for years 1-7 were, respectively, 99.42%, 97.26%, 94.57%, 92.41%, 90.48%, 88.63%, and 88.23%; thus with the 5-year survival at 90.48%. The corresponding data for DFS were 96.17%, 84.07%, 77.26%, 72.57%, 68.59%, 65.04%, and 63.05%, respectively; thus with the 5-year DFS at 68.59%. Adverse effects, with the exception of cardiac complications, occurred in 1194 (17%), while causing withdrawal of 421 (6%) patients. Most of other adverse events were related to hepatotoxicity 1755 (25%) and fatigue 681 (9.7%). Conclusion These results demonstrate the great benefits of inclusion of immunotherapy as the adjuvant component as currently the best overall therapeutic strategy for the patients suffering breast cancers. As this strategy greatly exceeds any other therapeutic options available for practicing oncologists at the present time, it definitely justifies allocation of all needed public resources, while assuring highest quality health service for the patients in Poland.

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