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.
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.
Neuzillet Y.,Hospital Foch |
Guy L.,Service dUrologie |
Long J.-A.,Grenoble University Hospital Center |
Zini L.,Lille University Hospital Center |
And 9 more authors.
Progres en Urologie | Year: 2011
Three clinical cases have shown the superiority of sunitinib in first line therapy intermediate risk metastatic clear cell renal carcinoma and a best safety of bevacizumab plus interferon, the current lack of high level of evidence arguments for the neo-adjuvant treatment of kidney cancer, the importance to prevent mucositis during a mTOR inhibitors treatment and the diagnostic pitfalls of its pulmonary complications. © 2011 Elsevier Masson SAS.
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.
Fizazi K.,University Paris - Sud |
Lesaunier F.,Center Franois Baclesse |
Delva R.,Center Paul Papin |
Gravis G.,Institute Paoli Calmettes |
And 24 more authors.
European Journal of Cancer | Year: 2012
Aim: To assess docetaxel-estramustine in patients with localised high-risk prostate cancer. Patients and methods: After staging pelvic lymph node dissection, patients with high-risk prostate cancer randomly received androgen deprivation therapy (ADT) (3 years) + DE (4 cycles of docetaxel 70 mg/m 2/3 weeks + estramustine 10 mg/kg/d d1-5) or ADT alone. Local therapy was administered at 3 months. Results: Four hundred and thirteen patients were accrued: T3-T4 (67%), Gleason score ≥8 (42%), PSA >20 ng/mL (59%), pN+ (29%). In the chemotherapy arm, 94% of patients received the planned four cycles of docetaxel. Local treatment consisted of radiotherapy in 358 patients (87%) (median dose 74 Gy in both arms). ADT was given for 36 months in both arms. A PSA response (PSA ≤0.2 ng/mL after 3 months of treatment) was obtained in 34% and 15% in the ADT + DE arm and in the ADT arm, respectively (p < 0.0001). Febrile neutropenia occurred in only 2%. Moderate to severe hot flashes occurred less often in the ADT + DE arm (2% versus 22%; p < 0.001). There was no toxicity-related death, no secondary leukaemia, and no excess second cancers. Chemotherapy had a negative impact on quality of life (global health status, p = 0.01; fatigue, p = 0.003; role functioning, p = 0.003; social functioning, p = 0.006) at 3 months but this effect disappeared at 1 year. Conclusion: Docetaxel-estramustine can be combined safely with standard therapy in high-risk prostate cancer, with a promising PSA response rate and no negative impact on quality of life after 1 year. Long-term follow-up is required to assess the impact on relapse and survival. © 2011 Elsevier Ltd. All rights reserved.
Recher C.,Toulouse 1 University Capitole |
Coiffier B.,University of Lyon |
Haioun C.,Hopital Henri Mondor |
Molina T.J.,University of Paris Descartes |
And 18 more authors.
The Lancet | Year: 2011
The outcome of diffuse large B-cell lymphoma has been substantially improved by the addition of the anti-CD20 monoclonal antibody rituximab to chemotherapy regimens. We aimed to assess, in patients aged 18-59 years, the potential survival benefit provided by a dose-intensive immunochemotherapy regimen plus rituximab compared with standard treatment plus rituximab. We did an open-label randomised trial comparing dose-intensive rituximab, doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone (R-ACVBP) with subsequent consolidation versus standard rituximab, doxorubicin, cyclophosphamide, vincristine, and prednisone (R-CHOP). Random assignment was done with a computer-assisted randomisation-allocation sequence with a block size of four. Patients were aged 18-59 years with untreated diffuse large B-cell lymphoma and an age-adjusted international prognostic index equal to 1. Our primary endpoint was event-free survival. Our analyses of efficacy and safety were of the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00140595. One patient withdrew consent before treatment and 54 did not complete treatment. After a median follow-up of 44 months, our 3-year estimate of event-free survival was 81 (95 CI 75-86) in the R-ACVBP group and 67 (59-73) in the R-CHOP group (hazard ratio [HR] 0·56, 95 CI 0·38-0·83; p=0·0035). 3-year estimates of progression-free survival (87 [95 CI, 81-91] vs 73 [66-79]; HR 0·48 [0·30- 0·76]; p=0·0015) and overall survival (92 [87-95] vs 84 [77-89]; HR 0·44 [0·28-0·81]; p=0·0071) were also increased in the R-ACVBP group. 82 (42) of 196 patients in the R-ACVBP group experienced a serious adverse event compared with 28 (15) of 183 in the R-CHOP group. Grade 3-4 haematological toxic effects were more common in the R-ACVBP group, with a higher proportion of patients experiencing a febrile neutropenic episode (38 [75 of 196] vs 9 [16 of 183]). Compared with standard R-CHOP, intensified immunochemotherapy with R-ACVBP significantly improves survival of patients aged 18-59 years with diffuse large B-cell lymphoma with low-intermediate risk according to the International Prognostic Index. Haematological toxic effects of the intensive regimen were raised but manageable. Groupe d'Etudes des Lymphomes de l'Adulte and Amgen. © 2011 Elsevier Ltd.
Lagrange J.-L.,University Paris Est Creteil |
Lagrange J.-L.,Center Antoine Lacassagne |
Bascoul-Mollevi C.,Center Val dAurelle |
Geoffrois L.,Center Alexis Vautrin |
And 8 more authors.
International Journal of Radiation Oncology Biology Physics | Year: 2011
Purpose: To evaluate bladder preservation and functional quality after concurrent chemoradiotherapy for muscle-invasive cancer in 53 patients included in a Phase II trial. Patient and Methods: Pelvic irradiation delivered 45Gy, followed by an 18-Gy boost. Concurrent chemotherapy with cisplatin and 5-fluorouracil by continuous infusion was performed at Weeks 1, 4, and 7 during radiotherapy. Patients initially suitable for surgery were evaluated with macroscopically complete transurethral resection after 45Gy, followed by radical cystectomy in case of incomplete response. The European Organization for Research and Treatment of Cancer quality of life questionnaire QLQ-C30, specific items on bladder function, and the Late Effects in Normal Tissues-Subjective, Objective, Management, and Analytic (LENT-SOMA) symptoms scale were used to evaluate quality of life before treatment and 6, 12, 24, and 36 months after treatment. Results: Median age was 68 years for 51 evaluable patients. Thirty-two percent of patients had T2a tumors, 46% T2b, 16% T3, and 6% T4. A visibly complete transurethral resection was possible in 66%. Median follow-up was 8 years. Bladder was preserved in 67% (95% confidence interval, 52-79%) of patients. Overall survival was 36% (95% confidence interval, 23-49%) at 8 years for all patients, and 45% (28-61%) for the 36 patients suitable for surgery. Satisfactory bladder function, according to LENT-SOMA, was reported for 100% of patients with preserved bladder and locally controlled disease 6-36 months after the beginning of treatment. Satisfactory bladder function was reported for 35% of patients before treatment and for 43%, 57%, and 29%, respectively, at 6, 18, and 36 months. Conclusions: Concurrent chemoradiation therapy allowed bladder preservation with tumor control for 67% patients at 8 years. Quality of life and quality of bladder function were satisfactory for 67% of patients. © 2011 Elsevier Inc Printed in the USA. All rights reserved.
Noal S.,Center Franois Baclesse |
Levy C.,Center Franois Baclesse |
Hardouin A.,Center Franois Baclesse |
Rieux C.,Center Franois Baclesse |
And 10 more authors.
International Journal of Radiation Oncology Biology Physics | Year: 2011
Purpose: Most patients with localized breast cancer (LBC) who take adjuvant chemotherapy (CT) complain of fatigue and a decrease in quality of life during or after radiotherapy (RT). The aim of this longitudinal study was to compare the impact of RT alone with that occurring after previous CT on quality of life. Methods and Materials: Fatigue (the main endpoint) and cognitive impairment were assessed in 161 CT-RT and 141 RT patients during RT and 1 year later. Fatigue was assessed with Functional Assessment of Cancer Therapy-General questionnaires, including breast and fatigue modules. Results: At baseline, 60% of the CT-RT patients expressed fatigue vs. 33% of the RT patients (p <0.001). Corresponding values at the end of RT were statistically similar (61% and 53%), and fatigue was still reported at 1 year by more than 40% of patients in both groups. Risk factors for long-term fatigue included depression (odds ratio [OR] = 6), which was less frequent in the RT group at baseline (16% vs. 28 %, respectively, p = 0.01) but reached a similar value at the end of RT (25% in both groups). Initial mild cognitive impairments were reported by RT (34 %) patients and CT-RT (24 %) patients and were persistent at 1 year for half of them. No biological disorders were associated with fatigue or cognitive impairment. Conclusions: Fatigue was the main symptom in LBC patients treated with RT, whether they received CT previously or not. The correlation of persistent fatigue with initial depressive status favors administering medical and psychological programs for LBC patients treated with CT and/or RT, to identify and manage this main quality-of-life-related symptom. © 2011 Elsevier Inc.
Delozier T.,Center Franois Baclesse
Journal de Gynecologie Obstetrique et Biologie de la Reproduction | Year: 2010
The discovery of breast cancer carcinoma sensitivity to estradiol (E) suppression is the starting point of hormonal treatment. Hormonal receptors (ER and PR) are the pathway of the action of estradiol on breast tumor cells. The detection of at least one of these two receptors is needed to classify a tumor as hormone sensitive. The hormonal treatment of breast cancer attempts to suppress the stimulating action of E on tumor cells. This can be done by decreasing E synthesis - ovarian suppression (OS) or aromatase inhibitors (AIs) - or by compelling with E on receptors - tamoxifen (TAM). In advanced breast cancer, hormonal treatment gives good response with few side effects. In young patient, the treatment is based on TAM. It could be associated with OS. In post-menopausal women, AIs are more potent than TAM. They are used in the first line treatment and TAM as a second line. Fulvestrant is not superior TAM or AIs. In the adjuvant setting, hormonal treatment gives a significant reduction of recurrence and death. In young patient, the treatment is based on TAM. It could be associated with OS. In post-menopausal patients, adjuvant treatment must include an AIs for at least one part of the treatment. A survey of bone density is necessary. © 2010 Elsevier Masson SAS. All rights reserved.