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Biomedical subjects

Isabelle Ray-Coquard

Publications and source records attributed to Isabelle Ray-Coquard.

30 records · Page 2Linked to original sources

[Docetaxel and ovarian cancer].

Docetaxel has exhibited substantial clinical activity against platinum, refrac- tory, paclitaxel resistant and previously untreated advanced ovarian cancer. As single agent, in advanced ovarian cancer patients previously treated with platinum agents, docetaxel 100 mg/m(2) every 3 weeks yields a 30% overall response rate and 6 months duration of response. In vitro data demonstrate a lack of complete cross-resistance bet- ween docetaxel and paclitaxel. In both platinum- and paclitaxel-pretreated patients, the highest response rates were obtained in patients with the longest interval of time since receipt of prior chemotherapy. Docetaxel currently is being intensively evaluated as a component of first line combination chemotherapy for ovarian cancer. Phase I-II have shown that docetaxel-platinum doublets are feasible and highly effective in the treatment of ovarian cancer, with docetaxel-carboplatin providing a more favorable safety profile compared with docetaxel-cisplatin, particularly with respect to neurotoxicity. The preliminary results of a phase III comparison of docetaxel-carboplatin versus paclitaxel-carboplatin support the clinical use of docetaxel-carboplatin as first line chemotherapy for stage IC to IV ovarian cancer, as it was shown to reduce the incidence of grade > 2 neurosensory toxicity compared to paclitaxel-carboplatin. Comparative overall survival and quality of life and more mature progression free survival data will be instrumental in determining the relative merits of docetaxel-carboplatin and paclitaxel-carboplatin as first line adjuvant therapy for ovarian cancer. The positive clinical experiences with docetaxel-provide a strong basis for continued investigation of docetaxel-carboplatin-based chemotherapy as component of advanced ovarian cancer management.

Antineoplastic Agents, Phytogenic↗

[Cyclooxygenase 2 and breast cancer. From biological concepts to therapeutic trials].

Cyclooxygenases (Cox) are prostaglandin synthetase enzymes which play a key role in mammary carcinogenesis. Several connections were demonstrated between Cox and a few oncogenes (v-src, v-Ha-ras, HER-2/neu, Wnt, p53 mutated), alimentary products (PUFAs), transcription factors (c-jun and c-fos), proapoptotic proteins [Bax et Bcl-x(L)] or antiapoptotic (Bcl-2), CYP19 aromatase gene, NFkappaB receptor (RANKL), angiogenesis (via VEGF, TXA2, oxid nitric synthetase, alphaVbeta3 integrin receptor), peroxisome gamma proliferator receptor (PPARgamma) and its ligand PGJ2 and with antitubuline chemotherapy drugs. No correlation of Cox2 expression with hormonal receptors was shown. In epidemiologic studies there is evidence of breast cancer risk reduction for women who take AINS for a long time. Alimentary factors like resveratrol or insaturated fat acid reduce Cox2 expression in animal and could be investigated in human studies. Clinical trials are planed with the anti Cox2 celecoxib for breast cancer prevention, in adjuvant setting, in metastatic situation combined with exemestane or antitubulin drugs or in neoadjuvant therapy.

Animals↗

[Organization and impact of the multidisciplinary committee in oncology].

Medical practices in oncology are expected to be more and more multidisciplinary, yet few articles studied how this may be concretely applied. This article is describing the functioning of a multidisciplinary specialized committee in a rare tumor. 219 medical cases during 26 meetings between 09/04/2003 and 14/02/2004 had been studied. Discussions had been observed, described and studied qualitatively and quantitatively. At the time of a national plan has been launched to impose obligatory the consultation of such committees before any treatment strategy, two lessons can be drawn from this case study. On the one hand, it shows that a multidisciplinary committee may be an organizational tool facilitating the emergence of collective decisions, since it may facilitate the formulation and the discussion of alternative options (72 cases out of 219). More generally, to take treatment decisions, members of the committee exchange arguments that deal mostly with clinical and psychological condition of the patient (50 cases out of 219), state-of-the-art knowledge (39 cases out of 219) and individual experience of the practitioners (33 cases out of 219). On the other hand, this article intends to underline that the creation of such committees cannot be considered as a sufficient condition to improve the quality of treatment decisions. Indeed, this case study shows that the quality of decisions does not only rely on the collective deliberation, but also on the individual and specific competencies of some members of the committee that other members admit.

Decision Making↗

[Cyclooxygenase 2 and breast cancer. From biological concepts to clinical trials].

Cyclooxygenases (Cox) are prostaglandin synthetase enzymes which play a key role in mammary carcinogenesis. Several connections were demonstrated between Cox and a few oncogenes (v-src, v-Ha-ras, HER-2\neu, Wnt, p53 mutated), alimentary products (PUFAs), transcription factors (c-jun and c-fos), proapoptotic proteins [Bax et Bcl-x(L)] or antiapoptotic (Bcl-2), CYP19 aromatase gene, NFkappaB receptor (RANKL), angiogenesis (via VEGF, TXA2, oxid nitric synthetase, alphaVbeta3 integrin receptor), peroxisome gamma proliferator receptor (PPARgamma) and its ligand PGJ2 and with antitubuline chemotherapy drugs. No correlation of Cox2 expression with hormonal receptors was shown. In epidemiologic studies there is evidence of breast cancer risk reduction for women who take AINS for a lon time. Alimentary factors like resveratrol or insaturated fat acid reduce Cox2 expression in animal and could be investigated in human studies. Clinical trials are planed with the anti Cox2 celecoxib for breast cancer prevention, in adjuvant setting, in metastatic situation combined with exemestane or antitubulin drugs or in neoadjuvant therapy.

Animals↗

Risk model predictive of severe anemia requiring RBC transfusion after chemotherapy in pediatric solid tumor patients.

PURPOSE: Severe anemias requiring RBC transfusions is a frequent complication of chemotherapy. A model elaborated by Ray-Coquard et al in adults pointed to three independent risk factors for RBC transfusion: performance status (PS) more than 1, hemoglobin less than 12 g/dL, and prechemotherapy absolute lymphocyte count (ALC) < or = 700/microL. This model is tested on a pediatric population. PATIENTS AND METHODS: One hundred nineteen children with solid tumors consecutively admitted for conventional chemotherapy throughout 1 year were included. The study end point was the RBC-transfusion risk in the month following chemotherapy. Only one course was considered for each patient. Age, sex, number of courses, platinum-containing regimens, PS, and hemoglobin and lymphocyte count at day 1 were tested in univariate and multivariate analyses. RESULTS: Thirty-one (26%) of 119 children required RBC transfusion within 31 days of chemotherapy. Three factors correlated to transfusion risk in the univariate analysis: PS more than 1 (P <.001), hemoglobin less than 12 g/dL (P =.007), and pretreatment ALC < or = 700/microL (P <.001). In the multivariate analysis, hemoglobin less than 12 g/dL, PS more than 1, and ALC < or = 700/microL were identified as independent factors predicting RBC transfusion. The calculated probability of receiving RBC transfusion within 31 days of chemotherapy was high with three risk factors (96%), intermediate with two risk factors (53% to 77%), low with one risk factor (10% to 26%), and very low when no risk factor was present (2%). The difference of transfusion needs was significant (P <.001). CONCLUSION: The risk model elaborated for adults may also segregate children at high risk of postchemotherapy RBC transfusion, thus facilitating assessment of risk of transfusion and/or prophylactic erythropoietin support.

Adolescent↗

Epirubicin and paclitaxel (EPI-TAX regimen) for advanced ovarian cancer after failure of platinum-containing regimens.

BACKGROUND: The place of anthracyclines in the treatment of advanced ovarian cancer remains a matter of debate. We have assessed the feasibility and evaluated the tolerance of epirubicin (EPI) combined with paclitaxel (TAX) in heavily pretreated ovarian cancer patients. METHODS: Between March 1996 and March 1998, 34 patients with ovarian cancer in relapse after platinum-based chemotherapy received EPI (75 mg/m(2)/day, iv) and TAX (175 mg/m(2)/day, 3-h infusion). Cycles were repeated every 3 weeks. This treatment was second-line for 10 patients and third/fourth-line for 24. RESULTS: Of the 34 assessable patients, 15 (44%) (95% confidence interval 27-60%) achieved objective response (3 complete and 12 partial responses). The number of previous lines of chemotherapy or previous anthracycline treatments did not influence response rates. Responders to previous paclitaxel-based regimens had a significantly higher response rate to EPI-TAX combination (57%) than nonresponders (11%) (P = 0.05). Median response duration was 40 weeks (range 12-94). Median survival from inclusion was 10.7 months (range 1-40). Myelosuppression was the most frequent side effect. Grade 3/4 neutropenia occurred in 31 patients (91%), febrile neutropenia episodes in 17%, and grade 3/4 anemia and thrombopenia in 27 and 24%, respectively. The main nonhematological toxicities included alopecia and grade 2 peripheral neuropathy (12%). Cardiac dysfunction was observed in one patient after the fourth treatment cycle. CONCLUSIONS: Toxicity of the EPI-TAX regimen was acceptable in this population of heavily pretreated ovarian cancer patients. The regimen was effective and it is considered an option for patients previously responding to paclitaxel-based therapy.

Adult↗

[Gastro-intestinal stromal tumors: news and comments].

Gastrointestinal stromal tumors (GIST) are rare tumors occuring at all levels of the gastrointestinal tract, whose estimated incidence may be close to 2 new cases per 100 000 persons per year. GIST derive from the interstital cells of Cajal (ICC) responsible for the motility of the GI tract, or from a common precursor of ICC and of the smooth muscle cells of the digestive tract. GIST cells express the c-kit protoconcogene under an activated form, either mutated or constitutively activated, as well as the CD34 Ag. Mutations of the KIT gene is an early event in the process of transformation in these tumors. Until recently, GIST were not recognized as a distinct entity among soft tissue sarcoma. It is now clear that conventional chemotherapy is generally inactive in this tumor, surgery being the only efficient therapeutic modality even in patients with advanced disease. Rapidly accruing phase I, II and III trials in the USA and Europe (EORTC) have demonstrated since 2000 that imatinib mesylate (STI571) is an active agent in GIST with an initial response rate of 70 % and 10 % only of primary refractory tumors, yelding an improved overall survival as compared to historical series. Resistance are now being observed however. GIST has become the first model of a solid tumor treated efficiently by a treatment targetting the initial genetic alteration of the disease. Numerous question regarding the integration of this treatment with surgery and the long term outcome of these patients still remain to be answered however.

Age Factors↗

[Anemia and chemotherapy].

Anemia is a real and frequent complication during the management of cancer patients. It is define as a decrease of the erythrocyte mass. The hemoglobin rate (which was an estimation of this erythrocyte mass) is the most often using criteria. The inferior threshold change with the sex and the age of the patients. This is 13 g/dl for the men and 11.5 g/dl for the women. This rate would be however decrease without any other associated pathology. This anemia is due to nutritional context of the patients and complications of the cancer pathology or his management (treatments). Anemia due to the chemotherapy toxicity is a real problem to investigate, to quantify, to prevent or to treat. The chemotherapy toxicity worsened previous anemia (inflammatory ethiology) which physiopathology is multifactoriel and depends on drugs, patients' characteristics, and sort of cancer. Anemia is also a therapeutic problem. Whatever is the severity of the anemia, impact on the quality of life with physical and social consequences is clear. In addition, anemia could relieve of specific treatment such as blood transfusion or preventive treatment with recombinant erythropoietin.

Age Factors↗

[Adjuvant therapy for breast cancer patients: treatment decision tree from a French cancer network].

Although the benefit of adjuvant therapy has largely been demonstrated for patients with local breast cancer, therapeutic indications remain controversial. The French regional cancer network Oncora investigated the decision-making process for this disease. Based on a thorough review of the literature, the risk of relapse and the potential benefit of adjuvant treatments for each group of patients were evaluated. A consensus decision-tree was drawn in which chemotherapy is proposed only to patients in whom it is expected to decrease the risk of relapse by at least 5 %. This approach, based on a widely accepted decision-making model, makes it possible to offer all patients of the network homogeneous treatment options. However, due to the subjectivity of risk/benefit estimations, patients themselves should become more involved in the decision-making process.

Age Factors↗

[Peritoneal carcinomatosis and hepatic infiltration related to the dissemination of a micropapillary cell carcinoma of the bladder].

Most cases of liver failure related to the infiltration of the liver by neoplastic cells are associated with hematological neoplasia or small cell carcinoma of the lung. We report case of liver failure related to a rare infiltration of the liver by a micropapillary bladder carcinoma. Micropapillary bladder cell carcinomas have recently been isolated among bladder tumors. They are characterized by life-threatening features as they spread rapidly to the interstitial stromal matrix leading to a highly aggressive course. The present case emphasizes the pathological features and poor prognosis of these neoplasia, as rapid submucosal spreading may prevent curative locoregional treatment.

Aged↗

[Clinical practice guidelines: Standards, Options and Recommendations for first line medical treatment of patients with ovarian neoplasms (summary report)].

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, which started in 1993, is a collaboration between the French Federation of Cancer Centers (FNCLCC), the 20 French Regional Cancer Centers, and specialists from French public universities, general hospitals and private clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and the outcome of cancer patients. OBJECTIVE: To update clinical practice guidelines for first line medical treatment of patients with ovarian neoplasms in collaboration with the French Society for Gynaecologica Oncology. METHODS: The methodology is based on a literature review and critical appraisal by a multidisciplinary group of experts. The CPGs are defined following the definitions of the Standards, Options and Recommendations project. Once the guideline has been developed, the document is submitted for review by independent reviewers. RESULTS: This article is a summary version of the full document presenting the clinical practice guidelines with algorithms. After surgery, most patients with ovarian neoplasms need adjuvant medical treatment. These guidelines concern the initial medical treatment (chemotherapy, hormone treatment and immunotherapy) and potential consolidation treatment. To complete the indications, two alternative treatment strategies are taken into account: no treatment and radiotherapy. This updated version concerns the indications and the modalities of chemotherapy. The main modifications are: 1) first-line chemotherapy for ovarian neoplasm can be taxane-platinum or carboplatine alone; 2) poly-chemotherapy is no longer a standard; 3) for early stages, except for stage IA grade I non-clear-cell tumours, adjuvant chemotherapy should be preferred to no treatment; 4) chemotherapy is standard for all stage III tumours, irrespective of the surgical result; 5) for stage IA G2-3 to IIA tumours, complete surgical staging and determination of the histological grade are standards.

Antineoplastic Agents↗