PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-7 (7)
 

Clipboard (0)
None

Select a Filter Below

Journals
Year of Publication
Document Types
author:("bujard, agate")
1.  Experimental designs for small randomised clinical trials: an algorithm for choice 
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.
doi:10.1186/1750-1172-8-48
PMCID: PMC3635911  PMID: 23531234
2.  Can treatment with Cocculine improve the control of chemotherapy-induced emesis in early breast cancer patients? A randomized, multi-centered, double-blind, placebo-controlled Phase III trial 
BMC Cancer  2012;12:603.
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-naïve 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.
doi:10.1186/1471-2407-12-603
PMCID: PMC3582626  PMID: 23244208
Early breast cancer; Adjuvant chemotherapy; Homeopathy; Nausea and vomiting; Quality of life
3.  Permanent 125I-seed prostate brachytherapy: early prostate specific antigen value as a predictor of PSA bounce occurrence 
Purpose
To evaluate predictive factors for PSA bounce after 125I permanent seed prostate brachytherapy and identify criteria that distinguish between benign bounces and biochemical relapses.
Materials and methods
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.
Results
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).
Conclusion
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.
doi:10.1186/1748-717X-7-46
PMCID: PMC3342157  PMID: 22449081
Brachytherapy; 125 iodine permanent seeds; Prostate cancer; PSA; Bounce; Biochemical relapse
4.  Validation of prognostic scores for survival in cancer patients beyond first-line therapy 
BMC Cancer  2011;11:95.
Background
We aimed to validate prognostic scores for survival in patients undergoing chemotherapy for advanced or metastatic cancer after first-line treatment.
Methods
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.
Results
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.
Conclusions
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.
doi:10.1186/1471-2407-11-95
PMCID: PMC3063819  PMID: 21406082
5.  Factors of interrupting chemotherapy in patients with Advanced Non-Small-Cell Lung Cancer 
BMC Research Notes  2010;3:164.
Background
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.
Findings
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.
Conclusion
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.
doi:10.1186/1756-0500-3-164
PMCID: PMC2904794  PMID: 20537187
6.  Outcome of recurrent and metastatic small cell carcinoma of the bladder 
BMC Urology  2009;9:4.
Background
Bladder small cell carcinoma is an uncommon tumour. Through a retrospective study we will present the evolution of recurrent and metastatic disease and outcome of patients treated at Léon-Bérard Cancer Centre.
Methods
Only 15 patients having recurrent or metastatic bladder small cell carcinoma were treated at Léon-Bérard Cancer Centre between 1996 and 2007. The patients were divided in two groups: a mixed small cell carcinoma group (9 patients) and a pure small cell carcinoma group (6 patients). All the records and informations related to treatment and outcome of the 15 patients were retrospectively analyzed. Various characteristics of small cell carcinoma were investigated.
Results
The median age of the 15 patients having recurrent or metastatic bladder small cell carcinoma and treated at Léon-Bérard Cancer Centre was 63 years and the disease was at stage IV for all cases. Nine patients were treated by chemotherapy. Four patients were treated by local radiotherapy (3 with radiotherapy without previous surgery and 1 with surgery followed by radiotherapy) and chemotherapy. One patient was treated by whole brain radiotherapy. And one patient died before treatment. After 52.4 months median follow up, 12 patients died. Median overall survival was 7.6 months. Survival probability at 1 year was 33%. Median overall survival was 9.9 months in the mixed small cell carcinoma group, and was only 4.6 months in the pure small cell carcinoma group. Survival probability at 1 year in the mixed small cell carcinoma group was 44% as compared to 17% in the pure small cell carcinoma group (Log-rank test: p = 0.228).
Conclusion
Recurrent and metastatic bladder small cell carcinoma is associated with very poor prognosis. The pure bladder small cell carcinoma appears to have poorer outcome than the mixed bladder small cell carcinoma. Chemotherapy using platinum drugs is a mainstay treatment.
doi:10.1186/1471-2490-9-4
PMCID: PMC2700133  PMID: 19500382
7.  A candidate molecular signature associated with tamoxifen failure in primary breast cancer 
Introduction
Few markers are available that can predict response to tamoxifen treatment in estrogen receptor (ER)-positive breast cancers. Identification of such markers would be clinically useful. We attempted to identify molecular markers associated with tamoxifen failure in breast cancer.
Methods
Eighteen initially ER-positive patients treated with tamoxifen requiring salvage surgery (tamoxifen failure [TF] patients) were compared with 17 patients who were disease free 5 years after surgery plus tamoxifen adjuvant therapy (control patients). cDNA microarray, real-time quantitative PCR, and immunohistochemistry on tissue microarrays were used to generate and confirm a gene signature associated with tamoxifen failure. An independent series of 33 breast tumor samples from patients who relapsed (n = 14) or did not relapse (n = 19) under tamoxifen treatment from a different geographic location was subsequently used to explore the gene expression signature identified.
Results
Using a screening set of 18 tumor samples (from eight control patients and 10 TF patients), a 47-gene signature discriminating between TF and control samples was identified using cDNA arrays. In addition to ESR1/ERα, the top-ranked genes selected by statistical cross-analyses were MET, FOS, SNCG, IGFBP4, and BCL2, which were subsequently validated in a larger set of tumor samples (from 17 control patients and 18 TF patients). Confirmation at the protein level by tissue microarray immunohistochemistry was observed for ER-α, γ-synuclein, and insulin-like growth factor binding protein 4 proteins in the 35 original samples. In an independent series of breast tumor samples (19 nonrelapsing and 14 relapsing), reduced expression of ESR1/ERα, IGFBP4, SNCG, BCL2, and FOS was observed in the relapsing group and was associated with a shorter overall survival. Low mRNA expression levels of ESR1/ERα, BCL2, and FOS were also associated with a shorter relapse-free survival (RFS). Using a Cox multivariate regression analysis, we identified BCL2 and FOS as independent prognostic markers associated with RFS. Finally, the BCL2/FOS signature was demonstrated to have more accurate prognostic value for RFS than ESR1/ERα alone (likelihood ratio test).
Conclusions
We identified molecular markers including a BCL2/FOS signature associated with tamoxifen failure; these markers may have clinical potential in the management of ER-positive breast cancer.
doi:10.1186/bcr2158
PMCID: PMC2614524  PMID: 18928543

Results 1-7 (7)