Agathe Bajard

Centre Léon Bérard, Lyons, Rhône-Alpes, France

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Publications (25)51.97 Total impact

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    ABSTRACT: BACKGROUND: Small clinical trials are necessary when there are difficulties in recruiting enough patients for conventional frequentist statistical analyses to provide an appropriate answer. These trials are often necessary for the study of rare diseases as well as specific study populations e.g. children. It has been estimated that there are between 6,000 and 8,000 rare diseases that cover a broad range of diseases and patients. In the European Union these diseases affect up to 30 million people, with about 50% of those affected being children. Therapies for treating these rare diseases need their efficacy and safety evaluated but due to the small number of potential trial participants, a standard randomised controlled trial is often not feasible. There are a number of alternative trial designs to the usual parallel group design, each of which offers specific advantages, but they also have specific limitations. Thus the choice of the most appropriate design is not simple. METHODS: PubMed was searched to identify publications about the characteristics of different trial designs that can be used in randomised, comparative small clinical trials. In addition, the contents tables from 11 journals were hand-searched. An algorithm was developed using decision nodes based on the characteristics of the identified trial designs. RESULTS: We identified 75 publications that reported the characteristics of 12 randomised, comparative trial designs that can be used in for the evaluation of therapies in orphan diseases. The main characteristics and the advantages and limitations of these designs were summarised and used to develop an algorithm that may be used to help select an appropriate design for a given clinical situation. We used examples from publications of given disease-treatment-outcome situations, in which the investigators had used a particular trial design, to illustrate the use of the algorithm for the identification of possible alternative designs. CONCLUSIONS: The algorithm that we propose could be a useful tool for the choice of an appropriate trial design in the development of orphan drugs for a given disease-treatment-outcome situation.
    Orphanet Journal of Rare Diseases 03/2013; 8(1):48. · 4.32 Impact Factor
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    ABSTRACT: BACKGROUND: Chemotherapy induced nausea and vomiting (CINV) remains a major problem that seriously impairs the quality of life (QoL) in cancer patients receiving chemotherapy regimens. Complementary medicines, including homeopathy, are used by many patients with cancer, usually alongside with conventional treatment. A randomized, placebo-controlled Phase III study was conducted to evaluate the efficacy of a complex homeopathic medicine, Cocculine, in the control of CINV in non-metastatic breast cancer patients treated by standard chemotherapy regimens. METHODS: Chemotherapy-naive patients with non-metastatic breast cancer scheduled to receive 6 cycles of chemotherapy including at least three initial cycles of FAC 50, FEC 100 or TAC were randomized to receive standard anti-emetic treatment plus either a complex homeopathic remedy (Cocculine, registered in France for treatment of nausea and travel sickness) or the matching placebo (NCT00409071 clinicaltrials.gov). The primary endpoint was nausea score measured after the 1st chemotherapy course using the FLIE questionnaire (Functional Living Index for Emesis) with 5-day recall. Secondary endpoints were: vomiting measured by the FLIE score, nausea and vomiting measured by patient self-evaluation (EVA) and investigator recording (NCI-CTC AE V3.0) and treatment compliance. RESULTS: From September 2005 to January 2008, 431 patients were randomized: 214 to Cocculine (C) and 217 to placebo (P). Patient characteristics were well-balanced between the 2 arms. Overall, compliance to study treatments was excellent and similar between the 2 arms. A total of 205 patients (50.9%; 103 patients in the placebo and 102 in the homeopathy arms) had nausea FLIE scores > 6 indicative of no impact of nausea on quality of life during the 1st chemotherapy course. There was no difference between the 2 arms when primary endpoint analysis was performed by chemotherapy stratum; or in the subgroup of patients with susceptibility to nausea and vomiting before inclusion. In addition, nausea, vomiting and global emesis FLIE scores were not statistically different at any time between the two study arms. The frequencies of severe (Grade >= 2) nausea and vomiting were low in our study (nausea: P: 17.6% vs C: 15.7%, p=0.62; vomiting: P: 10.8% vs C: 12.0%, p=0.72 during the first course). CONCLUSION: This double-blinded, placebo-controlled, randomised Phase III study showed that adding a complex homeopathic medicine (Cocculine) to standard anti-emetic prophylaxis does not improve the control of CINV in early breast cancer patients.
    BMC Cancer 12/2012; 12(1):603. · 3.33 Impact Factor
  • R. Mazeron, A. Bajard, P. Pommier
    Cancer/Radiothérapie 12/2012; 16(8):725. · 1.48 Impact Factor
  • R. Mazeron, A. Bajard, P. Pommier
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    ABSTRACT: Permanent seeds brachytherapy is a standard in the treatment of localized prostate cancer. Follow-up of patients treated with brachytherapy relies on monitoring the concentration of PSA. It is supposed to decrease steadily to a nadir after several years. This decrease could be disrupted by transient and benign elevation of the marker, sometimes mimicking genuine biochemical relapses, sources of anxiety for patients or even unnecessary tests. While the precise mechanisms of this phenomenon are poorly understood, their characteristics have been, however, extensively studied. This work aims to make an update on the current state of knowledge.
    Cancer/Radiothérapie 12/2012; 16(8):702–710. · 1.48 Impact Factor
  • R. Mazeron, A. Bajard, P. Pommier
    Cancer/Radiothérapie 12/2012; 16(8):722. · 1.48 Impact Factor
  • R Mazeron, A Bajard, P Pommier
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    ABSTRACT: Permanent seeds brachytherapy is a standard in the treatment of localized prostate cancer. Follow-up of patients treated with brachytherapy relies on monitoring the concentration of PSA. It is supposed to decrease steadily to a nadir after several years. This decrease could be disrupted by transient and benign elevation of the marker, sometimes mimicking genuine biochemical relapses, sources of anxiety for patients or even unnecessary tests. While the precise mechanisms of this phenomenon are poorly understood, their characteristics have been, however, extensively studied. This work aims to make an update on the current state of knowledge.
    Cancer/Radiothérapie 11/2012; · 1.48 Impact Factor
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    ABSTRACT: Infiltration and dysfunction of immune cells have been documented in many types of cancers. We previously reported that plasmacytoid dendritic cells (pDC) within primary breast tumors correlate with an unfavorable prognosis for patients. The role of pDC in cancer remains unclear but they have been shown to mediate immune tolerance in other pathophysiologic contexts. We postulated that pDC may interfere with antitumor immune response and favor tolerance in breast cancer. The present study was designed to decipher the mechanistic basis for the deleterious impact of pDC on the clinical outcome. Using fresh human breast tumor biopsies (N = 60 patients), we observed through multiparametric flow cytometry increased tumor-associated (TA) pDC (TApDC) rates in aggressive breast tumors, i.e., those with high mitotic index and the so-called triple-negative breast tumors (TNBT). Furthermore, TApDC expressed a partially activated phenotype and produced very low amounts of IFN-α following toll-like receptor activation in vitro compared with patients' blood pDC. Within breast tumors, TApDC colocalized and strongly correlated with TA regulatory T cells (TATreg), especially in TNBT. Of most importance, the selective suppression of IFN-α production endowed TApDC with the unique capacity to sustain FoxP3(+) Treg expansion, a capacity that was reverted by the addition of exogenous IFN-α. These findings indicate that IFN-α-deficient TApDC accumulating in aggressive tumors are involved in the expansion of TATreg in vivo, contributing to tumor immune tolerance and poor clinical outcome. Thus, targeting pDC to restore their IFN-α production may represent an attractive therapeutic strategy to overcome immune tolerance in breast cancer. Cancer Res; 72(20); 5188-97. ©2012 AACR.
    Cancer Research 07/2012; 72(20):5188-97. · 8.65 Impact Factor
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    ABSTRACT: OBJECTIVE: To evaluate the percentage of regional recurrence (RR) in patients with triple-negative (TN) N0 breast cancer in order to consider the interests of a systematic adjuvant nodal irradiation. PATIENTS AND METHODS: Between February 1996 and June 2009, 249 patients were treated for TN breast cancer in Léon-Bérard center (Lyon, France). All patients received first surgical treatment followed or not by chemotherapy or radiotherapy. We excluded patients with metastasis at diagnosis, patients who were initially irradiated regional lymph node, patients which ER, PR and/or HER2 status was not known and patients who didn't have standard treatment. Ultimately, 100 patients were included. RESULTS: Two patients (2%) developed regional recurrence (1 sub and supraclavicular recurrence and 1 supraclavicular recurrence). The median follow-up was 34 months (95% CI: 29,2 to 37,4). The survival rate at 3 years was 98% (95% CI: 90-99). Our study showed no differences in terms of RR between TN cancers and not TN cancers for a median followed up of 34 months. CONCLUSION: The results of our study do not suggest that patients with TN breast cancer should receive systematic nodal adjuvant radiotherapy.
    Gynécologie Obstétrique & Fertilité 07/2012; · 0.55 Impact Factor
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    ABSTRACT: To evaluate predictive factors for PSA bounce after 125I permanent seed prostate brachytherapy and identify criteria that distinguish between benign bounces and biochemical relapses. Men treated with exclusive permanent 125I seed brachytherapy from November 1999, with at least a 36 months follow-up were included. Bounce was defined as an increase ≥ 0.2 ng/ml above the nadir, followed by a spontaneous return to the nadir. Biochemical failure (BF) was defined using the criteria of the Phoenix conference: nadir +2 ng/ml. 198 men were included. After a median follow-up of 63.9 months, 21 patients experienced a BF, and 35.9% had at least one bounce which occurred after a median period of 17 months after implantation (4-50). Bounce amplitude was 0.6 ng/ml (0.2-5.1), and duration was 13.6 months (4.0-44.9). In 12.5%, bounce magnitude exceeded the threshold defining BF. Age at the time of treatment and high PSA level assessed at 6 weeks were significantly correlated with bounce but not with BF. Bounce patients had a higher BF free survival than the others (100% versus 92%, p = 0,007). In case of PSA increase, PSA doubling time and velocity were not significantly different between bounce and BF patients. Bounces occurred significantly earlier than relapses and than nadir + 0.2 ng/ml in BF patients (17 vs 27.8 months, p < 0.0001). High PSA value assessed 6 weeks after brachytherapy and young age were significantly associated to a higher risk of bounces but not to BF. Long delays between brachytherapy and PSA increase are more indicative of BF.
    Radiation Oncology 03/2012; 7:46. · 2.11 Impact Factor
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    ABSTRACT: OBJECTIVES. As vascular endothelial growth factor (VEGF) is expressed in ovarian cancer, we assessed the efficacy and safety of bevacizumab (a monoclonal antibody targeting VEGF) plus microtubule targeting agents for heavily pre-treated ovarian carcinoma patients. METHODS. We retrospectively reviewed 43 patients with recurrent epithelial ovarian carcinoma. Combined treatment included bevacizumab with paclitaxel in 32 (74%), docetaxel in 10 (23%), and vinorelbine in one (2.3%) patients, respectively. RESULTS. The median number of combined treatment was six cycles (range 1-29). On RECIST criteria, the objective response rate (ORR) was 40% (16% CR and 24% PR). Clinical benefit (complete response [CR] plus partial response [PR] and stable disease [SD] lasting ≥ 3 months) was 74% (CI95%: 46.7-77%). Median duration of treatment and overall survival were 3.9 months (range 0.2-14.4 months) and 20.1 months (CI95%: 13.8-20.1) respectively. No toxic death was reported. Grade 3-4 toxicity occurred in 30% of patients. Gastrointestinal perforations and fistula occurred in 3 (7%) and 6 (14%) patients, respectively. CONCLUSION. Although being active in terms of ORR, bevacizumab plus microtubule targeting agents - mainly taxanes - leads to a high rate of gastro-intestinal perforations and fistula in heavily pre-treated ovarian carcinoma patients.
    Bulletin du cancer 09/2011; 98(9):80-9. · 0.61 Impact Factor
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    ABSTRACT: In ovarian cancer, the immune system fails to eradicate established tumors partly due to the induction of immune tolerance within tumor microenvironment. In this study, we investigated the contribution of plasmacytoid dendritic cells (pDC) in the establishment of immune tolerance in a cohort of 44 ovarian cancer patients. In the tumor and malignant ascites, CD4(+)CD123(+)BDCA2(+) pDC were the most abundant dendritic cell subset; however, they were profoundly depleted in peripheral blood. The presence of pDC in primary ovarian cancer, but not ascites, was an independent prognostic factor associated with early relapse. Following chemotherapy, we observed a partial restoration of blood pDC levels in patients in complete remission. These findings show preferential recruitment of pDC into tumors where they express a partially mature phenotype that may reflect an in situ activation. Importantly, compared with pDC found in ascites or blood, tumor-associated pDC (TApDC) produced less IFN-α, TNF-α, IL-6, macrophage inflammatory protein-1β, and RANTES in response to toll-like receptor stimulation, and alterations in pDC functions were mainly mediated through tumor-derived TNF-α and TGF-β. Unlike ascites-derived pDC, TApDC induced IL-10 production from allogeneic naive CD4(+) T lymphocytes, suggesting the existence of a paracrine immunosuppressive loop. Taken together, our findings indicate that both local and systemic dysfunction of pDC play a critical role in the progression of ovarian cancer via induction of immune tolerance.
    Cancer Research 06/2011; 71(16):5423-34. · 8.65 Impact Factor
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    ABSTRACT: We aimed to validate prognostic scores for survival in patients undergoing chemotherapy for advanced or metastatic cancer after first-line treatment. We previously described two models with good prognostic value based on a combination of Performance Status (PS) and either lactate dehydrogenase (LDH) level or lymphocyte count. These factors were evaluated for their ability to predict overall survival (OS) in a prospective cohort of 299 patients. Clinical and blood parameters were prospectively recorded. Candidate prognostic factors for OS with 0.05 significance level in univariate analysis were included in a multivariate Cox model. Median age was 59 years (range: 26-85). Primary tumor sites were breast (45%), lung (15%), ovaries (11%) and others (29%). The number of metastatic sites was 1 (29%), 2 (48%), >2 (23%). Median follow-up and median OS were 12 and 6 months, respectively. Multiple regression analysis confirmed that PS >1, lymphocyte count ≤700/μL and LDH >600 UI/L were independent predictors of short OS, as well as interleukin 6 (IL-6) level, serum albumin concentration and platelet count. Prognostic scores using PS plus LDH level or PS plus lymphocyte count were validated for predicting survival in metastatic cancer patients in relapse beyond first-line treatment. A score combining PS, LDH, lymphocyte and platelet count, serum albumin and IL-6 level was superior in determining patients' prognosis.
    BMC Cancer 03/2011; 11:95. · 3.33 Impact Factor
  • European Journal of Cancer - EUR J CANCER. 01/2011; 47.
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    ABSTRACT: To assess the efficacy of capecitabine plus docetaxel (XT) versus epirubicin plus docetaxel (ET) as first-line therapy for metastatic breast cancer (MBC). Patients with no prior chemotherapy for MBC were randomized to 3-weekly cycles of either XT (capecitabine 1,000 mg/m(2) twice daily, days 1-14; docetaxel 75 mg/m(2), day 1) or ET (epirubicin 75 mg/m(2), day 1; docetaxel 75 mg/m(2), day 1). The primary endpoint was non-progression rate 6 months after randomization. The planned sample size was 106 patients based on a randomized, phase II selection design. Between April 2004 and January 2007, 68 patients were randomized, giving 82% power to select the best regimen according to a 6-month non-progression rate. Slow accrual led to premature study termination. Baseline characteristics were generally well balanced between arms. The 6-month non-progression rates were 75.8% with XT versus 65.7% with ET (p = 0.36). After 42 months' median follow-up, median progression-free survival was 12.4 versus 6.8 months, respectively (p = 0.040). The safety profiles were consistent with previous experience. Further larger studies are warranted to validate these results. Despite more grade 3 hand-foot syndrome, first-line XT may be a valid alternative to ET, potentially improving efficacy.
    Oncology 01/2011; 80(3-4):262-8. · 2.17 Impact Factor
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    ABSTRACT: Objective To evaluate the percentage of regional recurrence (RR) in patients with triple-negative (TN) N0 breast cancer in order to consider the interests of a systematic adjuvant nodal irradiation.Patients and methodsBetween February 1996 and June 2009, 249 patients were treated for TN breast cancer in Léon-Bérard center (Lyon, France). All patients received first surgical treatment followed or not by chemotherapy or radiotherapy. We excluded patients with metastasis at diagnosis, patients who were initially irradiated regional lymph node, patients which ER, PR and/or HER2 status was not known and patients who didn’t have standard treatment. Ultimately, 100 patients were included.ResultsTwo patients (2%) developed regional recurrence (1 sub and supraclavicular recurrence and 1 supraclavicular recurrence). The median follow-up was 34 months (95% CI: 29,2 to 37,4). The survival rate at 3 years was 98% (95% CI: 90–99). Our study showed no differences in terms of RR between TN cancers and not TN cancers for a median followed up of 34 months.Conclusion The results of our study do not suggest that patients with TN breast cancer should receive systematic nodal adjuvant radiotherapy.
    Cancer Radiotherapie - CANCER RADIOTHER. 01/2011; 15(6):576-576.
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    ABSTRACT: Objective To analyse the evolution of nutritional parameters after cancer surgery in the elderly, to review patient management practices and evaluate risk factors of postoperative complications.
    Nutrition Clinique Et Metabolisme - NUTR CLIN METAB. 01/2011; 25(1):5-13.
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    ABSTRACT: Little is known about prognosis of metastatic patients after receiving a first-line treatment and failure. Our group already showed in pre-treated patients enrolled in phase I clinical trials that a performance status (PS) > 2 and an LDH > 600 UI/L were independent prognostic factors. In this prospective study, which included 45 patients, we identified clinical and biological variables as outcome predictors in metastatic Non-Small Cell lung cancer after first line chemotherapy were identified. Forty-five patients that were previously treated for metastatic disease from 12/2000 to 11/2005 in the comprehensive cancer centre (Centre Léon Bérard). Clinical assessment and blood parameters were recorded and considered. Patient prognostic factors for overall survival (OS) with a 0.05-significance level in univariate analysis were entered in a multivariate Cox model for further analysis.Patients' median age was 58.5 years (range: 37 - 76). Sixty two percent of the patients were PS = 0 or 1. After inclusion, nine patients received second-line (22.5%), and two received third-line chemotherapy (5%). Univariate analysis showed that the factors associated with reduced OS were: PS > 2, weight loss >10%, more than one line of chemotherapy treatment and abnormal blood parameters (hemoglobin (Hb), platelet and neutrophils counts). Multiple regression analysis confirmed that PS > 2 and abnormal hemoglobin were independent predictors for low overall survival. According to the presence of none (33%), 1 (37%) and 2 (30%) prognostic factors, median OS were 12, 5 and 2 months respectively. From this prospective study, both PS and anemia were found as independent determinants of survival, we found that both PS and anemia were independent determinants of survival. The combination of poor PS and anemia is an effective strategy to predict survival in the case of patients with metastatic NSCLC receiving further treatment after the first line.
    BMC Research Notes 01/2010; 3:164.
  • Fuel and Energy Abstracts 01/2010; 78(3).
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    ABSTRACT: Adjuvant chemotherapy has frequently been associated with weight gain after breast cancer diagnosis. We aimed to prospectively evaluate body weight variations in French patients with early breast cancer. This prospective observational study included 272 breast cancer patients who were candidates for adjuvant chemotherapy. Weight and body mass index were measured at baseline visit, then at 9 and 15 months from baseline (6 and 12-month post-chemotherapy). At baseline visit, information on the benefits of weight gain prevention and healthy diet was given by a dietician. Univariate logistic regression was performed to test the association between weight gain and potential predictive factors. Thirty percent of patients gained weight during the year before diagnosis, 26% were overweight and 15% were obese. At one year, the mean weight change was +1.5kg (SD=4.1) and +2.3% (SD=6.0); 60% of the cohort had gained weight, with a median increase of 3.9kg (SD=3.0) and 5.9% (SD=4.4). Reported weight gain during the year before diagnosis appears to be the only factor associated with the absence of post-chemotherapy weight gain (OR=0.54, 95% CI [0.31-0.95], p=0.034). Body weight increased in the post-chemotherapy period in French breast cancer survivors, even when given dietary recommendations. Appropriate weight management interventions with nutritional follow-up and physical activity programs are needed.
    Clinical nutrition (Edinburgh, Scotland) 09/2009; 29(2):187-91. · 3.27 Impact Factor
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    ABSTRACT: The Evidence Based Medicine (EBM) paradigm requires that results from Randomized Controlled Trials (RCTs) must be assessed for validity before being assimilated. However, evaluating available evidence is often still based on intuitive processes rather than on rigorous scientific analysis. To establish a hierarchy among the different factors influencing the level of evidence of RCT results, using a Monte Carlo simulation. The complete RCT model involved three submodels: i) the input-output submodel for the prediction of events (using the sigmoid dose-response relationship as the basic model), ii) the execution submodel for deviations from a randomized, controlled two-arm parallel trial related to either patient-specific or investigator-specific elements or both: placebo or nocebo effect, errors of measurement, effect of concomitant therapy, regression to the mean phenomenon, blinding process, loss to follow-up and randomization process, iii) the covariate distribution submodel. The most important factors influencing discrepancies in the true-to-observed odds ratio were the blinding process, the measurement errors (affecting either the therapeutic or the adverse effects), the placebo effect, the effect of concomitant therapies and to a less extent the randomization process. Whereas the randomization process remained the only relevant factor in double-blinded trials, the hierarchy of other factors was modified according to the type of blinding. In RCTs, the hierarchy of confounding factors differs according to the type of blinding and the current short list of components of the strength of evidence (poorly concealed randomization and lack of blinding) appears to be incomplete.
    Contemporary clinical trials 08/2009; 30(5):400-10. · 1.51 Impact Factor

Publication Stats

135 Citations
51.97 Total Impact Points

Institutions

  • 2009–2013
    • Centre Léon Bérard
      Lyons, Rhône-Alpes, France
  • 2012
    • Institut de Cancérologie Gustave Roussy
      • Department of Radiotherapy
      Île-de-France, France