Randomized multicenter and stratified phase II study of gemcitabine alone versus gemcitabine and docetaxel in patients with metastatic or relapsed leiomyosarcomas: A fédération nationale des centres de lutte contre le cancer (FNCLCC) french sarcoma group study (TAXOGEM study)
Floquet A.,Institute Bergonie |
Penel N.,Center Oscar Lambret |
Piperno-Neumann S.,University Pierre and Marie Curie |
Isambert N.,Center Georges Franois Leclerc |
And 7 more authors.
Oncologist | Year: 2012
Background. This study aimed to evaluate the efficacy and toxicity of single-agent gemcitabine versus gemcitabine plus docetaxel as second-line therapy in patients with uterine and nonuterine leiomyosarcoma (LMS). Patients and Methods. Patients had metastatic or unresectable LMS and had received one prior anthracyclinebasedregimen.Atotalof90patientsreceivedeithersingleagent gemcitabine (arm A; gemcitabine, 1,000 mg/m2i.v. for 100 minutes on days 1, 8, and 15 of a 28-day cycle) or a combination of gemcitabine and docetaxel (arm B; gemcitabine, 900 mg/m2i.v. for 90 minutes on days 1 and 8, plus docetaxel, 100 mg/m2i.v. for 1 hour on day 8 of a 21-day cycle with lenograstim). The primary endpoint was the objective response rate. Results.Theobjectiveresponserateswere19%and24% in arm A (gemcitabine) and arm B (gemcitabine plus docetaxel), respectively, for patients with uterine LMS. For patientswithnonuterineLMS,theobjectiveresponserates were14%and5%forarmsAandB,respectively.Themedianprogression-freesurvivaltimesforarmsAandBwere 5.5 months and 4.7 months, respectively, for patients with uterine LMS. For patients with nonuterine LMS, the median progression-free survival times were 6.3 months and 3.8monthsforarmsAandB,respectively.Onetoxicdeath occurred in arm B. Conclusions. Both single-agent gemcitabine and gemcitabine plus docetaxel were found to be effective second-line therapies for leiomyosarcomas, with a 3-month progression-freesurvivalrateof40%forLMSwithboth uterine and nonuterine sites of origin. Single-agent gemcitabine yielded results similar to those of gemcitabine plus docetaxel in this trial, but patients using single-agent gemcitabine experienced less toxicity. © AlphaMed Press.
Bolla M.,Center Hospitalier University |
Hannoun-Levi J.M.,Center Antoine Lacassagne |
Ferrero J.-M.,Center Antoine Lacassagne |
Maingon P.,Center Georges Franois Leclerc |
And 7 more authors.
Radiotherapy and Oncology | Year: 2010
Background and purpose: We evaluate the feasibility of concomitant and adjuvant docetaxel combined with three-dimensional conformal radiotherapy (3D-CRT) and androgen deprivation in high-risk prostate carcinomas. Methods: Fifty men with high-risk localized prostate cancer (16), locally advanced (28) or very high-risk prostate cancer (6) were included. Seventy Gy were delivered on prostate and seminal vesicles in 35 fractions, concurrently with weekly docetaxel (20 mg/m2). Three weeks after the completion of 3D-CRT, docetaxel was given for 3 cycles (60 mg/m2), every 3 weeks. Patients had to receive LHRH agonist during 3 years. Results: The intent to treat analysis shows that four patients out of 15 stopped prematurely the chemotherapy due to grade 3-4 acute toxicity. In the per protocol analysis, 46 patients completed a full-dose chemoradiation regimen representing 413 cycles: five patients experienced a grade 3 toxicity, and 15 patients experienced a grade 2 toxicity. With a median follow-up of 54 months, the 5-year clinical disease-free survival was 66.72% and the 5-year survival was 92.15%. Conclusions: 3D-CRT with androgen deprivation and concurrent weekly docetaxel, followed by three cycles of adjuvant docetaxel may be considered as feasible in high-risk prostate cancer and deserved to be evaluated in a phase III randomized trial. © 2010 Elsevier Ireland Ltd. All rights reserved.
Randomized phase III trial (GORTEC 98-03) comparing re-irradiation plus chemotherapy versus methotrexate in patients with recurrent or a second primary head and neck squamous cell carcinoma, treated with a palliative intent
Tortochaux J.,Center Jean Perrin |
Tao Y.,Institute Gustave Roussy |
Tournay E.,Institute Gustave Roussy |
Lapeyre M.,Center Jean Perrin |
And 11 more authors.
Radiotherapy and Oncology | Year: 2011
Purpose: This randomized phase III trial investigated the potential benefit of concurrent re-irradiation, fluorouracil and hydroxyurea versus methotrexate for patients treated with palliative intent for recurrent or second primary head and neck squamous cell carcinoma (HNSCC) in previously irradiated area. Patients and methods: Patients with recurrent HNSCC or a second primary not amenable to curative-intent treatment were randomized to the R-RT arm (concurrent re-irradiation, fluorouracil and hydroxyurea) or to the Ch-T arm (methotrexate). The primary endpoint was overall survival (OS). Due to a very slow accrual, the trial was closed after inclusion of 57 patients. Results: Fifty-seven patients were included. All patients died in the two arms with a maximal follow-up of 5 years. Although four complete responses were achieved in R-RT arm, (none in Ch-T arm) re-irradiation did not improve OS compared with methotrexate (23% versus 22% at 1 year, NS). Sixteen patients experienced clinical grade ≥3 late toxicities (>6 months), 11 in R-RT arm and five in Ch-T arm. Conclusions: Premature discontinuation of the trial did not allow us to draw firm conclusions. However, there was no suggestion that concurrent re-irradiation, fluorouracil and hydroxyurea improved OS compared to methotrexate alone in patients treated with palliative intent for a recurrent or second primary HNSCC. © 2011 Elsevier Ltd. All rights reserved.
Ghiringhelli F.,French Institute of Health and Medical Research |
Ghiringhelli F.,University of Burgundy |
Ghiringhelli F.,Center Georges Franois Leclerc |
Bruchard M.,French Institute of Health and Medical Research |
And 5 more authors.
Journal of Biomedicine and Biotechnology | Year: 2012
It is now well known that tumor immunosurveillance contributes to the control of cancer growth. Many mechanisms can be used by cancer cells to avoid the antitumor immune response. One such mechanism relies on the capacity of cancer cells or more generally of the tumor microenvironment to generate adenosine, a major molecule involved in antitumor T cell response suppression. Adenosine is generated by the dephosphorylation of extracellular ATP released by dying tumor cells. The conversion of ATP into adenosine is mediated by ectonucleotidase molecules, namely, CD73 and CD39. These molecules are frequently expressed in the tumor bed by a wide range of cells including tumor cells, regulatory T cells, Th17 cells, myeloid cells, and stromal cells. Recent evidence suggests that targeting adenosine by inhibiting ectonucleotidases may restore the resident antitumor immune response or enhance the efficacy of antitumor therapies. This paper will underline the impact of adenosine and ectonucleotidases on the antitumor response. © 2012 Franois Ghiringhelli et al.
Guilcher M.A.-L.,Center Rene Gauducheau |
Prevost B.,Center Oscar Lambret |
Sunyach M.P.,Center Leon Berard |
Peiffert D.,Center Alexis Vautrin |
And 7 more authors.
International Journal of Radiation Oncology Biology Physics | Year: 2011
Purpose: To evaluate the efficacy and toxicity of high-dose-rate (HDR) brachytherapy in patients with inoperable endobronchial carcinoma. Methods and Materials: We retrospectively reviewed the records (April 1991 - May 2004) of patients with non-small-cell carcinoma, with no extrabronchial spread on computed tomography scans, who underwent HDR brachytherapy because of contraindications to surgery and external beam radiation therapy. Kaplan-Meier survival curves were compared by the log-rank test. Prognostic factors were analyzed by multivariate analysis. Results: 226 patients (223 men, 3 women, mean age: 62.2 years (range, 40-84)) were included. Of those, 217 (97%) had squamous cell carcinoma (Tis/T1/T2/Tx: 60/153/9/4). Dose was prescribed at 1 cm from the radius (24-35 Gy in 4-6 fractions). Mean follow-up was 30.4 months (range, 9-116). Complete endoscopic response rate was 93.6% at 3 months. One hundred twenty-eight patients (56%) died of intercurrent disease (n = 45), local failure (n = 36), metastasis (n = 10), local failure and metastasis (n = 11), complications (n = 13), and other causes (n = 12). The 2-year and 5-year survival rates were, respectively, 57% and 29% (overall) (median, 28.6 months), 81% and 56% (cancer-specific), and 68% and 50% (local disease-free). Acute toxicity included pneumothorax (1.5%) and mucosal inflammation (10%). Late complications were hemoptysis (6.6% with 5% of fatalities), bronchitis (19.5%), and necrosis (3.5%). In multivariate analysis, a distal tumor location and the use of two catheters were associated with improved local disease-free survival (p = 0.003 and p = 0.007, respectively) and a distal tumor location with improved overall survival (p = 0.0001). Conclusions: This large retrospective study confirms that HDR brachytherapy is an efficient and safe treatment in patients with inoperable endobronchial carcinoma. Copyright © 2011 Elsevier Inc.
Alentorn A.,Groupe Hospitalier Pitie Salpetriere |
Alentorn A.,Paris-Sorbonne University |
Alentorn A.,French Institute of Health and Medical Research |
Alentorn A.,French National Center for Scientific Research |
And 50 more authors.
Neurology | Year: 2015
Objectives: We aimed to study the potential clinical relevance of 9p allelic loss, with or without copy number variation, in 1p/19q codeleted anaplastic oligodendroglial tumors (AOTs). Methods: This study enrolled 216 patients with 1p/19q codeleted AOT. The prognostic value of 9p allelic loss was investigated using a French nation-wide prospective registry, POLA (prise en charge des tumeurs oligodendrogliales anaplasiques) and high-density single nucleotide polymorphism arrays. We validated our results using the Repository of Molecular Brain Neoplasia Data (REMBRANDT) dataset. Results: The minimal common region of allelic loss in chromosome arm 9p was 9p21.3. Allelic loss of 9p21.3, detected in 41.7% of tumors, was associated with shorter progression-free and overall survival rates in univariate (p 5 0.008 and p , 0.001, respectively) and multivariate analyses (p 5 0.009 and p 5 0.009, respectively). This finding was validated in the REMBRANDT dataset in univariate and multivariate analysis (p 5 0.01 and p 5 0.01, respectively). Conclusion: Our study highlights a novel potential prognostic biomarker in 1p/19q codeleted AOT. Further prospective studies are warranted to investigate our finding. © 2015 American Academy of Neurology.
Retroperitoneal lymphadenectomy and survival of patients treated for an advanced ovarian cancer: The CARACO trial [Impact des curages rétropéritonéaux sur la survie des patientes atteintes dun cancer de lovaire un stade avancé : le protocole CARACO]
Classe J.-M.,Center Rene Gauducheau |
Cerato E.,Center Rene Gauducheau |
Boursier C.,Center Rene Gauducheau |
Dauplat J.,Center Jean Perrin |
And 8 more authors.
Journal de Gynecologie Obstetrique et Biologie de la Reproduction | Year: 2011
The standard management for advanced-stage epithelial ovarian cancer is optimum cytoreductive surgery followed by platinum based chemotherapy. However, retroperitoneal lymph node resection remains controversial. The multiple directions of the lymph drainage pathway in ovarian cancer have been recognized. The incidence and pattern of lymph node involvement depends on the extent of the disease and the histological type. Several published cohorts suggest the survival benefit of pelvic and para-aortic lymphadenectomy. A recent large randomized trial have demonstrated the potential benefit for surgical removal of bulky lymph nodes in term of progression-free survival but failed to show any overall survival benefit because of a critical methodology. Further randomised trials are needed to balance risks and benefits of systematic lymphadenectomy in advanced-stage disease. CARACO is a French ongoing trial, built to bring a reply to this important question. A huge effort for inclusion of the patients, and involving new teams, are mandatory.