Deutsch E.,Institute Gustave Roussy |
Lemanski C.,CRLC Val DAurelle |
Pignon J.P.,Institute Gustave Roussy |
Levy A.,Institute Gustave Roussy |
And 12 more authors.
Annals of Oncology | Year: 2013
Background: The ACCORD 16 phase II trial aimed to evaluate the objective response rate after combination of conventional chemoradiotherapy (CRT) and cetuximab in locally advanced anal canal carcinoma (LAACC).Patients and methods: Immunocompetent patients with histologically confirmed LAACC received CRT [45 gray (Gy)] in 25 fractions over 5 weeks, fluorouracil and cisplatin during weeks 1 and 5), in combination with weekly dose of cetuximab (250 mg/m2 with a loading dose of 400 mg/m2 1 week before irradiation), and a standard dose boost (20 Gy). The trial was originally designed to include 81 patients to detect a 15% of objective response increase with the new combination in comparison with CRT. Results: The trial was prematurely stopped after the declaration of 15 serious adverse events (SAEs) in 14 out of 16 patients. Five patients received the entire planned treatment, and the compliance was higher after amendments of the protocol. Among the 15 SAEs, 6 were unexpected. Grade (G) 3/4 acute toxic effects, observed in 88% patients, were general (n = 13, 81%), digestive (n = 9, 56%), dermatological (n = 5, 31%), infectious (n = 4, 25%), haematological (n = 3, 19%), and others (n = 9); and three patients suffered from six G3/4 late toxic effects. No treatment-related death was reported. All 11 assessable patients had an objective response consisting of six complete (55%) and five partial (45%) response 2 months after the end of the treatment. Thirteen patients were followed up with a median of 22 months [95% confidence interval (CI): 18-27] and had a 1-year colostomy-free survival, progression-free and overall survival rate of 67% (95% CI: 40%-86%), 62% (95% CI: 36%-82%), and 92% (95% CI: 67%-99%), respectively. Conclusion: CRT plus cetuximab was unacceptably toxic in this population of patients. Results of others phase II trials evaluating this combination are awaited to confirm these findings. © The Author 2013. Published by Oxford University Press on behalf of the European Society for Medical Oncology All rights reserved.
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.
Robertson J.F.R.,Royal Derby Hospital |
Ferrero J.-M.,Center Antoine Lacassagne |
Bourgeois H.,Clinique Victor Hugo |
Kennecke H.,British Columbia Cancer Agency |
And 9 more authors.
The Lancet Oncology | Year: 2013
Background: Insulin-like growth factors (IGF-1 and IGF-2) bind to the IGF-1 receptor (IGF-1R), increasing cell proliferation and survival. Ganitumab is a monoclonal IgG1 antibody that blocks IGF-1R. We tested the efficacy and safety of adding ganitumab to endocrine treatment for patients with hormone-receptor-positive breast cancer. Methods: We did this phase 2 trial in outpatient clinics and hospitals. We enrolled postmenopausal women with hormone-receptor-positive, locally advanced or metastatic breast cancer previously treated with endocrine treatment. They were randomly assigned (2:1) with a central randomisation schedule to receive intravenous ganitumab 12 mg per kg bodyweight or placebo in combination with open-label intramuscular fulvestrant (500 mg on day 1, then 250 mg on days 15, 29, and every 28 days) or oral exemestane (25 mg once daily) on a 28-day cycle. Patients, investigators, study monitors, and the sponsor staff were masked to treatment allocation. Response was assessed every 8 weeks. The primary endpoint was median progression-free survival in the intention-to-treat population. We analysed overall survival as one of our secondary endpoints. The study is registered at ClinicalTrials.gov, number NCT00626106. Findings: We screened 189 patients and enrolled 156 (106 in the ganitumab group and 50 in the placebo group). Median progression-free survival did not differ significantly between the ganitumab and placebo groups (3·9 months, 80% CI 3·6-5·3 vs 5·7 months, 4·4-7·4; hazard ratio [HR] 1·17, 80% CI 0·91-1·50; p=0·44). However, overall survival was worse in the the ganitumab group than in the placebo group (HR 1·78, 80% CI 1·27-2·50; p=0·025). With the exception of hyperglycaemia, adverse events were generally similar between groups. The most common grade 3 or higher adverse event was neutropenia-reported by six of 106 (6%) patients in the ganitumab group and one of 49 (2%) in the placebo group. Hyperglycaemia was reported by 12 of 106 (11%) patients in the ganitumab group (with six patients having grade 3 or 4 hyperglycaemia) and none of 49 in the placebo group. Serious adverse events were reported by 27 of 106 (25%) patients in the ganitumab group and nine of 49 (18%) patients in the placebo group. Interpretation: Addition of ganitumab to endocrine treatment in women with previously treated hormone-receptor-positive locally advanced or metastatic breast cancer did not improve outcomes. Our results do not support further study of ganitumab in this subgroup of patients. Funding: Amgen. © 2013 Elsevier Ltd.
Denouel A.,CRLC Val dAurelle
Methods in molecular biology (Clifton, N.J.) | Year: 2011
Molecular analysis of tissue lesions is increasingly used in laboratories to identify new prognostic and therapeutic markers. Formalin has long been the tissue fixative of choice in the laboratories of pathology, as it preserves tissue morphology allowing accurate histological diagnosis. However, formalin is highly toxic and alters nucleic acids and protein integrity, so that new fixatives are critically needed that would allow both morphological and molecular analysis on the same tissue specimen. Recently, we found RCL2(®)-CS100, a noncross-linking fixative, to display interesting performances regarding tissue morphology and DNA, RNA, and protein quality. We adapted RCL2 tissue fixation protocol so it could be used on a routine and automated laboratory basis, still preserving its good performances. This protocol will be described in detail in the following review.
Millet I.,Montpellier University |
Bouic-Pages E.,Montpellier University |
Hoa D.,Montpellier University |
Azria D.,CRLC Val dAurelle |
Taourel P.,Montpellier University
BMC Cancer | Year: 2011
Background: Women with a personal history of breast cancer have a high risk of developing an ipsi- or contralateral recurrence. We aimed to compare the growth rate of primary breast cancer and recurrences in women who had undergone prior breast magnetic resonance imaging (MRI).Methods: Three hundred and sixty-two women were diagnosed with breast cancer and had undergone breast MRI at the time of diagnosis in our institution (2005 - 2009). Among them, 37 had at least one prior breast MRI with the lesion being visible but not diagnosed as cancer. A linear regression of tumour volume measured on MRI scans and time data was performed using a generalized logistic model to calculate growth rates. The primary objective was to compare the tumour growth rate of patients with either primary breast cancer (no history of breast cancer) or ipsi- or contralateral recurrences of breast cancer.Results: Twenty women had no history of breast cancer and 17 patients were diagnosed as recurrences (7 and 10 were ipsi- and contralateral, respectively). The tumour growth rate was higher in contralateral recurrences than in ipsilateral recurrences (growth rate [10-3days-1] 3.56 vs 1.38, p < .001) or primary cancer (3.56 vs 2.09, p = 0.01). Differences in tumour growth were not significant for other patient-, tumour- or treatment-related characteristics.Conclusions: These findings suggest that contralateral breast cancer presents accelerated growth compared to ipsilateral recurrences or primary breast events. © 2011 Millet et al; licensee BioMed Central Ltd.
Complete response for rectal carcinoma after neoadjuvant therapy: To operate or not to operate? Surgeons view [Réponse tumorale complète des cancers du rectum après traitement néoadjuvant: Faut-il opérer? Point de vue du chirurgien]
Rouanet P.,CRLC Val dAurelle
Bulletin du Cancer | Year: 2011
A complete response to neoadjuvant therapy occurs in a significant group of patients with rectal cancer. Management of these patients is controversial. This review evaluates the tumoral response, the surgical management and the potential results. ©John Libbey Eurotext.
Assenat E.,CRLC Val dAurelle |
Thezenas S.,Val dAurelle Cancer Institute |
Flori N.,CRLC Val dAurelle |
Pere-Charlier N.,Val dAurelle Cancer Institute |
And 4 more authors.
Journal of Pain and Symptom Management | Year: 2011
Context: Few studies have evaluated outcomes of combined chemoradiotherapy for Stage III-IV head and neck squamous cell carcinoma in terms of the use of nutritional support by means of percutaneous endoscopic gastrostomy (PEG). Objectives: To compare nutritional status and treatment interruption because of acute toxicity in patients with advanced head and neck tumors who were treated by combined chemoradiotherapy and received or did not receive prophylactic PEG tubes. Methods: This was a retrospective study that evaluated data obtained from a cancer center in Montpellier, France. A total of 139 consecutive patients treated for Stage III-IV head and neck squamous cell carcinoma from January 1, 1998 to June 30, 2003 were evaluated in terms of nutritional status before and after therapy, treatment interruption because of toxicity, and duration of hospitalization. Results: Seventy-eight of the 139 patients (58%) did not receive prophylactic PEG feeding, and 61 patients (44%) received PEG feeding. Pretreatment nutritional status was worse in the PEG group. Compared with the initial nutritional status, nutritional status at the end of treatment was unchanged in the PEG group and much worse in the group that did not receive the PEG (P < 0.05). Cumulative incidence of treatment interruption because of toxicity was significantly lower in the PEG group than in the no-PEG group (100 and 236 days of interruption, respectively, P = 0.03) and hospitalization was significantly shorter (P = 0.003). Conclusion: Prophylactic PEG sustains nutritional status and reduces the cumulative incidence of treatment interruption caused by toxicity and duration of hospitalization. A randomized study is warranted to validate these results. © 2011 U.S. Cancer Pain Relief Committee Published by Elsevier Inc. All Rights reserved.
Quenet F.,CRLC Val DAurelle |
Goere D.,CNRS Gustave Roussy Institute |
Mehta S.S.,CRLC Val DAurelle |
Roca L.,CRLC Val DAurelle |
And 4 more authors.
Annals of Surgery | Year: 2011
Objective: To assess the perioperative and long-term results of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) using oxaliplatin+irinotecan (ox-irino) versus oxaliplatin alone (ox-alone). Background: Treatment of peritoneal carcinomatosis (PC) of colorectal origin with CRS+HIPEC using mitomycin-C or oxaliplatin monotherapy has shown encouraging survival results. This bi-centric study evaluates an intensified intraperitoneal combination of ox-irino and compares it with ox-alone. PATIENTS AND Methods: All consecutive patients with PC undergoing CRS+HIPEC using either ox-alone or ox-irino between1998 and 2007 were evaluated. Results: One hundred forty-six patients underwent CRS+HIPEC for PC, 103 received ox-irino and 43 received ox-alone. The median peritoneal carcinomatosis index (PCI) was 11 in both groups. 90.4% had complete cytoreduction. Overall mortality rate was 4.1%. The overall morbidity rate was 47.2% and was significantly lower with ox-alone (34.9% vs. 52.4%, P = 0.05). After a median follow-up of 48.5months, the median overall survival (OS) was 41months (95% CI, 32-60) and median relapse-free survival (RFS) was 15.7 months (95% CI, 12-18). The median RFS of ox-alone (16.8 months; 95% CI, 11-25) was not significantly different from ox-irino (15.7 months; 95% CI, 11-18; P = 0.93). There was no significant difference between median OS of ox-alone (40.83 months; 95%CI, 29-61) and ox-irino (47 months; 95%CI, 32-61; P = 0.94). At 5 years, OS and RFS rates were 41.8% and 13.8% in ox-alone and 42.4% and 14.2% in ox-irino, respectively. Prognostic factors confirmed on multivariate analysis were lymph node metastasis and PCI. Conclusion: Our study showed no advantage of intensification of HIPEC by adding irinotecan, contrary to the results obtained with IV combination. Ox-alone HIPEC should continue as one of the standard HIPEC regimens for PC. Copyright © 2011 by Lippincott Williams & Wilkins.
Pouessel D.,CRLC Val dAurelle
Bulletin du cancer | Year: 2010
Radical cystectomy with bilateral pelvic lymph node dissection is the standard of care for patients with muscle-invasive bladder cancer, with 5-year survival rates not exceeding 60%. Consequently a multidisciplinary approach including perioperative chemotherapy and/or radiation therapy is required to improve these results. Data from clinical trials and meta-analyses with neoadjuvant chemotherapy have shown a significant benefit in overall survival, with a 5% absolute benefit at five years, provided cisplatin-based combination chemotherapy is used. Reported trials do not support the routine use of adjuvant chemotherapy. The current role of radiation therapy is limited to highly selected cases with a combination of external radiotherapy, partial cystectomy and interstitial brachytherapy.
Azria D.,CRLC Val dAurelle |
Belkacemi Y.,AP HP |
Romieu G.,CRLC Val dAurelle |
Gourgou S.,CRLC Val dAurelle |
And 9 more authors.
The Lancet Oncology | Year: 2010
Background: Letrozole radiosensitises breast cancer cells in vitro. In clinical settings, no data exist for the combination of letrozole and radiotherapy. We assessed concurrent and sequential radiotherapy and letrozole in the adjuvant setting. Methods: This phase 2 randomised trial was undertaken in two centres in France and one in Switzerland between Jan 12, 2005, and Feb 21, 2007. 150 postmenopausal women with early-stage breast cancer were randomly assigned after conserving surgery to either concurrent radiotherapy and letrozole (n=75) or sequential radiotherapy and letrozole (n=75). Randomisation was open label with a minimisation technique, stratified by investigational centres, chemotherapy (yes vs no), radiation boost (yes vs no), and value of radiation-induced lymphocyte apoptosis (≤16% vs >16%). Whole breast was irradiated to a total dose of 50 Gy in 25 fractions over 5 weeks. In the case of supraclavicular and internal mammary node irradiation, the dose was 44-50 Gy. Letrozole was administered orally once daily at a dose of 2·5 mg for 5 years (beginning 3 weeks pre-radiotherapy in the concomitant group, and 3 weeks post-radiotherapy in the sequential group). The primary endpoint was the occurrence of acute (during and within 6 weeks of radiotherapy) and late (within 2 years) radiation-induced grade 2 or worse toxic effects of the skin. Analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00208273. Findings: All patients were analysed apart from one in the concurrent group who withdrew consent before any treatment. During radiotherapy and within the first 12 weeks after radiotherapy, 31 patients in the concurrent group and 31 in the sequential group had any grade 2 or worse skin-related toxicity. The most common skin-related adverse event was dermatitis: four patients in the concurrent group and six in the sequential group had grade 3 acute skin dermatitis during radiotherapy. At a median follow-up of 26 months (range 3-40), two patients in each group had grade 2 or worse late effects (both radiation-induced subcutaneous fibrosis). Interpretation: Letrozole can be safely delivered shortly after surgery and concomitantly with radiotherapy. Long-term follow-up is needed to investigate cardiac side-effects and cancer-specific outcomes. Funding: Novartis Oncology France. © 2010 Elsevier Ltd. All rights reserved.