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Biomedical subjects

Sylvie Négrier

Publications and source records attributed to Sylvie Négrier.

16 recordsLinked to original sources

Why don't cancer patients enter clinical trials? A review.

Despite widespread agreement about the value of clinical trials, the proportion of patients who are enrolled in such trials is often considered to be too low. A comprehensive literature search was carried out for the period 1980 to the present, in order to review current data on barriers and facilitators to the development of multicentre clinical trials. Of 364 articles initially identified, 35 articles and 1 book were selected in order to assess the reasons that doctors and/or patients participate in clinical trials. This review emphasises the fact that doctors play a key role in the development and non-development of clinical trials. More studies, in particular studies outside the United States of America (USA), are needed in order better to understand doctors' attitudes towards clinical trials. Such studies should combine multivariate analyses and comparative approaches in order to associate doctors' behaviours with their individual characteristics, with the organisational context of their working environment and with the healthcare system.

Attitude of Health Personnel↗

Nonmetastatic renal-cell carcinoma: is it really possible to define rational guidelines for post-treatment follow-up?

Defining rational follow-up guidelines in patients treated for cancer is important, from both a medical and an economical perspective. Renal-cell carcinoma is reputed to be unpredictable in its course and only a few, and often contradictory, follow-up guidelines exist for patients treated for nonmetastatic renal-cell carcinoma. Recent advances in tumor biology have contributed to a better understanding of this cancer and have indicated that personalized follow-up regimens, based on tumor and host molecular characteristics, might be possible in the near future.

Biomarkers, Tumor↗

[New entities in pathological classification and new therapeutic options in renal cell carcinoma].

Therapy for renal cell carcinoma has made considerable progress in the past few years. The aims of this review are to update the pathological classification of this tumor and discuss predictive factors for tumor response and survival in the case of metastasis as well as the place of immunotherapy with interleukine-2 and/or interferon alpha . Furthermore, we will review new therapeutic options and current results on allogeneic stem cell transplantation with non-myeloablative conditioning and HLA genoidentical donors. Finally, we will present targeted therapy (antiangiogenic drugs and tyrosine kinase inhibitors) with the mechanisms of action, efficacy and appropriate use in the treatment of metastatic renal cell carcinoma.

Angiogenesis Inhibitors↗

[Clinical practice guideline: 2005 update of recommendations for the management of patients with cutaneous melanoma without distant metastases (summary report)].

CONTEXT: The National French federation of comprehensive cancer centres (FNCLCC) and the French society of dermatology (SFD) initiated together the update of clinical practice guideline for the management of patients with cutaneous melanoma in collaboration with the French national cancer institute and with specialists from French public universities, general hospitals and private clinics. This work is based on the methodology developed in the "Standards, Options and Recommendations" (SOR) project. OBJECTIVES: To update SOR guidelines for the management of patients with cutaneous melanoma previously validated in 1998 and French melanoma consensus conference published by SFD and ANAES in 1995. METHODS: The methodology is based on a literature review and critical appraisal by a multidisciplinary group of experts who define the CPGs according to the definitions of the Standards, Options and Recommendations project. Once the guidelines have been developed, they are reviewed by independent reviewers. RESULTS: This article is a summary version of the updated clinical practice guidelines with algorithms. The main questions addressed by the expert group in this update concerned (1) The new AJCC-UICC classification (2) Excision margins (3) Sentinel node biopsy (4) Adjuvant treatments (5) Initial staging and follow up of operated patients.

Algorithms↗

Protein chip array profiling analysis of sera from neuroblastoma patients.

Neuroblastoma, the most common extracranial solid tumour in children, is characterised by highly heterogeneous clinical behaviour; patients are stratified into risk categories according to a combination of clinical and biological markers. However, identifying non-invasive prognostic markers predicting outcome independently from current risk-stratification features remains critical for better disease monitoring. Using the SELDI-TOF-MS technology (surface-enhanced laser desorption/ionization time-of-flight mass spectrometry), we found a serum biomarker that strongly correlates with prognosis in neuroblastoma patients. Subsequent peptide mapping identified this biomarker as SAA protein. In support of this observation, high SAA levels were detected by ELISA in the sera of patients with poor prognosis neuroblastoma. Based on this finding, promises and limitations of the approach are discussed.

Enzyme-Linked Immunosorbent Assay↗

Tumoral and immunologic response after vaccination of melanoma patients with an ALVAC virus encoding MAGE antigens recognized by T cells.

PURPOSE: To evaluate the toxicity, antitumoral effectiveness, and immunogenicity of repeated vaccinations with ALVAC miniMAGE-1/3, a recombinant canarypox virus containing a minigene encoding antigenic peptides MAGE-3(168-176) and MAGE-1(161-169), which are presented by HLA-A1 and B35 on tumor cells and can be recognized by cytolytic T lymphocytes (CTLs). MATERIALS AND METHODS: The vaccination schedule comprised four sequential injections of the recombinant virus, followed by three booster vaccinations with the MAGE-3(168-176) and MAGE-1(161-169) peptides. The vaccines were administered, both intradermally and subcutaneously, at 3-week intervals. RESULTS: Forty patients with advanced cancer were treated, including 37 melanoma patients. The vaccines were generally well tolerated with moderate adverse events, consisting mainly of transient inflammatory reactions at the virus injection sites. Among the 30 melanoma patients assessable for tumor response, a partial response was observed in one patient, and disease stabilization in two others. The remaining patients had progressive disease. Among the patients with stable or progressive disease, five showed evidence of tumor regression. A CTL response against the MAGE-3 vaccine antigen was detected in three of four patients with tumor regression, and in only one of 11 patients without regression. CONCLUSION: Repeated vaccination with ALVAC miniMAGE-1/3 is associated with tumor regression and with a detectable CTL response in a minority of melanoma patients. There is a significant correlation between tumor regression and CTL response. The contribution of vaccine-induced CTL in the tumor regression process is discussed in view of the immunologic events that could be analyzed in detail in one patient.

Adult↗

Treatment of liver metastases from uveal melanoma.

BACKGROUND: Uveal melanoma patients with liver metastases have a poor prognosis. The effect of screening and multimodality treatment (including surgery) should be evaluated. METHODS: A total of 602 patients treated for uveal melanoma during a 14-year period had abdominal ultrasonography screening every 6 months. Sixty-three developed liver metastases as the first extraocular metastatic site. When possible, liver surgery and intra-arterial catheter implantation were performed. The influence on survival of demographics, uveal tumor characteristics, liver metastasis presentation, and treatment was studied. RESULTS: The median time to liver metastasis was 29 months. Twenty-eight patients (44%) were operated on: 14 (22%) had R0 liver surgery, and 14 with diffuse liver involvement had R2 liver surgery (there were no significant surgical complications). Thirty-five patients with diffuse liver involvement received systemic chemotherapy or best supportive care only. The median overall survival was 15 months (range, 3-110 months): 25 months for the 14 patients with R0 surgery, 16 months for the 14 with R2 surgery, and 11 months for the 35 with chemotherapy or supportive care. By univariate analysis, age (< or =70 years), number of metastases (< or =10), and quality of operation (R0) were predictive of a better prognosis. CONCLUSIONS: In the case of liver metastases from uveal melanoma, aggressive treatment permitting tumor eradication seems to offer a chance of long-term survival to selected patients. Nevertheless, neither ultrasound screening nor quality of operation had an effect on the outcome of most patients (78%). Better screening tests and more effective multimodality treatments are required to improve survival in uveal melanoma patients with hepatic metastases.

Adult↗

[Disseminated melanoma treatment].

Disseminated melanoma is an incurable disease whose prognosis has remained unchanged over the past 20 years. To date, no consensus treatment has emerged. No treatment strategy has proved superior to dacarbazine (Deticene) monochemotherapy that remains considered as the reference treatment for this disease. Both multidrug chemotherapy and biochemotherapy have provided disappointing results, with poorer quality of life and no survival benefit for the patients. Other treatment approaches, particularly immunotherapy, remain to be investigated in clinical trials.

Antineoplastic Agents, Alkylating↗

[Kidney tumors].

Explore the source record for details and available documents.

Humans↗

Cisplatin in combination with either gemcitabine or irinotecan in carcinomas of unknown primary site: results of a randomized phase II study--trial for the French Study Group on Carcinomas of Unknown Primary (GEFCAPI 01).

PURPOSE: To evaluate the efficacy and toxicity of novel chemotherapy combinations including cisplatin with gemcitabine (GC) or irinotecan (IC) for patients with carcinomas of an unknown primary site. PATIENTS AND METHODS: Eighty patients were randomly assigned to receive GC or IC. In the GC arm, chemotherapy consisted of cycles combining gemcitabine 1,250 mg/m2 intravenously (IV) on days 1 and 8, and cisplatin 100 mg/m2 IV on day 1 at 3-week intervals. Patients in the IC arm originally received 3-week cycles of irinotecan 200 mg/m2 IV on day 1 and cisplatin 80 mg/m2 IV on day 1. After the inclusion of 15 patients in that arm, the toxicity profile required the irinotecan doses to be reduced to 150 mg/m2 per cycle. Independent histologic and radiologic reviews were done. RESULTS: A total of 78 patients were assessable for efficacy and toxicity. The median number of cycles was four in each arm. Objective responses were observed in 21 patients (55%) in the GC arm (95% CI, 34% to 66%) and in 15 patients (38%) in the IC arm (95% CI, 23% to 54%). Treatment had to be stopped because of toxicity in seven patients in the GC arm and in eight patients in the IC arm. With a median follow-up of 22 months, the median survivals were 8 and 6 months in the GC and IC arms, respectively. CONCLUSION: This study demonstrates the activity of both the GC and IC regimens. There was toxicity associated with both regimens. Additional studies of combination chemotherapy regimens are required.

Adult↗

Subcutaneous interleukin-2 and interferon alpha in the treatment of patients with metastatic renal cell carcinoma-Less efficacy compared with intravenous interleukin-2 and interferon alpha. Results of a multicenter Phase II trial from the Groupe Français d'Immunothérapie.

BACKGROUND: The main objective of this trial was to evaluate the combination of subcutaneous (SC) interleukin-2 (IL-2) with interferon alpha-2a (IFN-alpha) in the treatment of patients with metastatic renal cell carcinoma (MRCC) compared with a previous trial that used continuous-infusion IL-2 and IFN-alpha with identical schedules and dosages. METHODS: Between April, 1997 and January, 1998, 66 patients with MRCC received SC IL-2 at a dose of 9 x 10(6) IU/m(2) twice daily for 5 days during 2 induction cycles and during 4 additional cycles, with a 3-week rest between cycles. Each induction cycle consisted of two 5-day courses of IL-2 separated by a 9-day break. IFN-alpha at a dose of 6 x 10(6) IU per day three times per week was given during induction cycles and additional cycles. RESULTS: All patients were assessable for response and toxicity. The median follow-up was 43 months. Thirty-five patients (51%) and 43 patients (63%) received >or= 80% of the planned induction doses of IL-2 and IFN-alpha, respectively. Five patients achieved objective responses (7.6%; 95% confidence interval [95%CI], 2.5-16.8%), with two complete responses. The median survival was 14 months (95%CI, 11.3-16.7 months). Fifty-three patients (80%) had at least one episode of Grade 3 toxicity related to treatment. Twenty-two patients developed Grade 4 toxicities, which included hypotension (24% of patients), decreased performance status (6% of patients), dyspnea (3% of patients), and mucositis (3% patients) as well as fever, ventricular tachycardia, and anemia. CONCLUSIONS: The current results seem to indicate reduced efficacy and higher toxicity rates with SC IL-2 plus IFN-alpha compared with the results from a previous trial that used an identical regimen with IV IL-2 administration. Although SC IL-2 regimens are used widely, their interest remains to be determined.

Adult↗

Combination of neoadjuvant chemotherapy with cryotherapy and surgical resection for the treatment of unresectable liver metastases from colorectal carcinoma.

BACKGROUND: This retrospective study was conducted to assess the safety, efficacy, and long-term results of neoadjuvant chemotherapy and cryotherapy as additional means for eradicating liver metastases from colorectal carcinoma when curative treatment was not possible by resection alone. METHODS: Between January 1996 and December 1997, 131 patients with unresectable liver metastases were referred to our department and received chemotherapy. After 3-6 months of chemotherapy, curative surgery of liver metastases was considered possible in 57 patients, either by resection alone in 33 patients (25%) or cryotherapy associated with resection in 24 patients (18%). Characteristics and survival of patients in the cryotherapy plus resection group were compared with those of the 33 patients in the resection group. RESULTS: All patients in the resection group had partial response to neoadjuvant chemotherapy. In the cryotherapy plus resection group, neoadjuvant chemotherapy resulted in 13 partial responses, 9 stable diseases, and 2 disease progressions. The rate of postoperative complications in the entire series was 14%. No major difference was seen between the two groups. After a median follow-up of 48 months, the median survival time was 39 months. The survival rates at 1, 3, and 4 years were similar in both groups: 94, 58, and 37% in the resection group and 92, 50, and 36% in the cryotherapy plus resection group, respectively. CONCLUSIONS: The combination of neoadjuvant chemotherapy, cryotherapy, and liver resection constitutes a promising treatment strategy for patients with extremely advanced metastatic liver involvement. Patients having more than four liver metastases from a colorectal carcinoma or patients with a poor liver reserve due to previous resection should be screened carefully to determine whether they could be candidates for this procedure.

Adult↗

A phase II study of docetaxel-irinotecan combination in advanced pancreatic cancer.

BACKGROUND/AIMS: Chemotherapy provides dismal results in advanced pancreatic cancer patients, even when new compounds, such as gemcitabine, are used. Phase I studies of single-drug therapy with docetaxel or irinotecan suggested a response rate of about 15% in these patients. We report here a phase II study of docetaxel-irinotecan combination in advanced pancreatic cancer patients. METHODOLOGY: Docetaxel 60 mg/m2 was given in combination with irinotecan 250 mg/m2 every 3 weeks. Prednisolone premedication and anti-HT3 drugs were systematically administered. Hematopoietic growth factors were given in case of febrile neutropenia or grade 4 neutropenia at the previous cycle. Endpoints were response rate, progression-free survival, and tolerance. RESULTS: Twenty-seven patients were enrolled, of whom 25 had metastatic disease. We observed 3 partial responses and 11 stabilizations. The median progression-free survival was 4.3 months. Myelosuppression was the main toxicity with 18% of patients experiencing a grade 3-4 event. One patient died of neglected febrile neutropenia. Gastrointestinal toxicity was well controlled. Other toxicities were mild. CONCLUSIONS: This combination has acceptable tolerance and, despite an 11% response rate, some partial responses and prolonged stabilizations were observed. The treatment induced clinical benefit in 33% of the patients. Further trials should focus on docetaxel or irinotecan, possibly used in combination with more conventional strategies (gemcitabine).

Adenocarcinoma↗