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Ray-Coquard I.,Center Leon Berard | Favier L.,Center Georges Francois Leclerc | Weber B.,Center Alexis Vautrin Brabois | Roemer-Becuwe C.,Oracle Inc. | And 7 more authors.
British Journal of Cancer | Year: 2013

Background: Patients with recurrent/metastatic endometrial cancer that progresses after chemotherapy have limited treatment options and poor outcomes. Preclinical data suggest the oral mammalian target of rapamycin inhibitor everolimus may provide clinical benefit in these patients. Methods: In this multicenter, open-label, phase 2 study, patients with advanced or metastatic endometrial cancer refractory to one or two previous chemotherapy regimens received everolimus 10 mg per day until progression or unacceptable toxicity. Primary end point was the non-progressive disease rate at 3 months. Secondary end points included duration of response, progression-free, and overall survival (OS), and safety. Results: Forty-four patients were enrolled (median age, 65 years); 66% received one previous chemotherapy regimen. The 3-month non-progressive disease rate was 36% (95% confidence interval 22-52%), including two patients (5%) with partial response (PR). At 6 months, two additional patients experienced PR. Median duration of response was 3.1 months. Median progression-free and OS were 2.8 months and 8.1 months, respectively. The most common adverse events were anaemia (100%), fatigue (93%), hypercholesterolaemia (81%), and lymphopenia (81%). Conclusion: Everolimus demonstrated efficacy and acceptable tolerability in patients with chemotherapy-refractory advanced or metastatic endometrial cancer. These results support the further development of phosphatidylinositol 3-kinase-targeted therapies in endometrial cancer. © 2013 Cancer Research UK. All rights reserved.

Ray-Coquard I.,Center Leon Berard | Weber B.,Center Alexis Vautrin | Lotz J.P.,Hopital Tenon | Tournigand C.,Hopital St. Antoine | And 6 more authors.
Gynecologic Oncology | Year: 2010

Background: Non-epithelial ovarian cancers are rare; their natural history is poorly understood and prognostic factors remain unclear. A French website (www.ovaire-rare.org) was developed to collect clinical cases and tumour samples in order to better define prognostic factors and develop specific trials. We report the results of the first 100 patients with germ cell (GCT) and sex cord-stromal (SCT) tumours. Methods: All adult patients with histological evidence of GCT or SCT at diagnosis or first relapse were eligible. Results: From 03/2002 to 06/2009, 180 patients were included; the first 100 were evaluated. Patient characteristics were: histology: SCT 61%, GCT 30%, others 5%; median age: 43 years; median tumour size: 12 cm; FIGO stages I-II: 83%, III-IV: 17%. Central pathology review (67 patients) differed from initial diagnosis in 37%. Fifty-six percent of the patients had initial conservative surgery and 10% lymph node dissection; 56 patients received chemotherapy. Eleven of the 78 first-line patients relapsed and 5 died; the 5-year OS rate was 94% and the median PFS 64 months. Conclusions: This online observatory allows assessing medical practice for GCT and SCT in France. Histological discrepancies between diagnosis and second opinion confirm the need for systematic review before treatment. Extension to other rare gynaecologic malignancies is on-going. © 2010 Elsevier Inc.

Lortholary A.,Center Catherine Of Sienne | Largillier R.,Center Azureen Of Cancerologie | Weber B.,Center Alexis Vautrin | Gladieff L.,Institute Claudius Regaud | And 5 more authors.
Annals of Oncology | Year: 2012

Background: Platinum rechallenge or weekly topotecan in combination have not been evaluated in randomized trials for resistant recurrent ovarian cancer (ROC). Methods: Patients with ROC after first- or second-line treatment including a platinum and taxane and progression within 6 months were randomized to weekly paclitaxel (wP, 80 mg/m. 2/week) alone or in combination with carboplatin (C, area under the curve of 5 mg/ml/min every 4 weeks) or weekly topotecan (wT, 3 mg/m 2/week). Primary end point was progression-free survival (PFS) comparing wP and combination therapy. Results: Patients (n = 165) received a median three cycles in each arm. Nonhematologic toxicity was not different, except increased hypersensitivity reactions with wP + C. Grade 3-4 hematologic toxic effects with wP, wP + C, and wP + wT, respectively, were neutropenia in 13%, 54%, and 42%; febrile neutropenia in 0%, 4%, and 5%; and anemia in 6%, 19%, and 29%. Response rates were 35%, 37%, and 39%, and median PFS times were 3.7, 4.8, and 5.4 months, respectively. PFS was not significantly different among the treatment arms [hazard ratio (HR) 0.922; 95% confidence interval (CI) 0.765-1.111; P = 0.46] or between monotherapy and combination therapy (HR 0.951; 95% CI 0.686-1.318; P = 0.76). Conclusions: Combination chemotherapy in platinum-resistant ROC was more toxic than weekly paclitaxel and did not significantly prolong PFS. © The Author 2011. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

Lortholary A.,Center Catherine Of Sienne | Hardy-Bessard A.-C.,Clinique Armoricaine de Radiologie | Bachelot T.,Center Leon Berard | Alexandre J.,University of Paris Descartes | And 4 more authors.
Breast Cancer Research and Treatment | Year: 2012

To determine whether capecitabine schedule adaptation improves the tolerability of capecitabine-paclitaxel combination therapy for metastatic breast cancer (MBC), patients with anthracycline-pretreated HER2-negative MBC were randomized to either arm A (21-day cycles: capecitabine 1,000 mg/m 2 twice daily, days 1-14; paclitaxel 60 mg/m 2, days 1, 8, and 15) or arm B (28-day cycles: capecitabine 1,000 mg/m 2 twice daily, days 1-5, 8-12, and 15-19; paclitaxel 80 mg/m 2, days 1, 8, and 15). The primary endpoint was the incidence of dose reductions or delays >1 week for grade 3/4 toxicity. Secondary endpoints were efficacy and safety. All 130 randomized patients were evaluable for safety. Dose reduction or delay for grade 3/4 toxicity occurred in 39% of patients in arm A and 34% in arm B during cycles 1-6. In arm A, there were significantly more toxicity-related dose reductions (cycles 1-6: 82 vs. 67%, respectively; P = 0.05) and discontinuations (29 vs. 8%, respectively). Grade 3 diarrhea occurred in 12 and 0%, respectively, and grade 3 hand-foot syndrome in 12 versus 9%, respectively (grade 4 not applicable). There were no detectable differences in efficacy. Weekday capecitabine dosing with weekly paclitaxel may improve tolerability without a detrimental effect on efficacy, and merits further evaluation in patients suited to combination chemotherapy. © 2011 Springer Science+Business Media, LLC.

Falandry C.,University of Lyon | Brain E.,Institute Curie Site Hopital Rene Huguenin | Bonnefoy M.,Center Hospitalier Lyon Sud | Mefti F.,Institute Curie Site Hopital Rene Huguenin | And 10 more authors.
European Journal of Cancer | Year: 2013

Metastatic breast cancer chemotherapy in the elderly is considered effective in carefully selected patients, but there is little data regarding its effect in vulnerable patients. Methods We evaluated tumour response (primary endpoint), feasibility and outcomes after six courses of an adapted dose of pegylated liposomal doxorubicin (PLD) (40 mg/m2 every 28 days) as first-line chemotherapy for hormone-resistant MBC. Results Of 60 patients >70 years (median 77 years), 15% had performance status ≥2 and 73% had visceral metastases. Geriatric assessment included: ≥2 comorbidities, 42%; ≥1 deficiency in Activities of Daily Living (ADL), 10% and Instrumental ADL (IADL), 82%; living in residential homes, 12%; albumin <35 g/L, 17%; body mass index (BMI) <21, 20%; depression, 17%; and lymphocytes ≤1 × 10 3/mm3, 27%. Complete response, partial response and stable disease were observed in 5%, 15% and 60%, respectively, but only 48% completed six cycles. Treatment discontinuations were mostly due to disease progression (18%) and non-haematological (NH) toxicities (22%). Eight patients died during treatment (three possibly related to PLD), and 15 had unplanned hospital admissions. Exploratory analyses to identify geriatric covariates associated with treatment outcomes revealed severe haematological toxicities significantly correlated with lymphocytes ≤1 × 103/mm3. NH toxicities correlated with age ≥80 years and living in residential homes. Progression-free survival (median 6.1 months) decreased with age, deficiency in IADL, cardiac dysfunction and living in residential homes. Overall survival (median 15.7 months) also decreased with living in residential homes. Conclusion Despite manageable haematological toxicities and expected response rates, PLD feasibility was poor in unselected elderly patients. © 2013 Elsevier Ltd. All rights reserved.

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