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1.
Ann Oncol ; 29(1): 133-138, 2018 01 01.
Article in English | MEDLINE | ID: mdl-29045659

ABSTRACT

Background: Metastatic colorectal cancer frequently occurs in elderly patients. Bevacizumab in combination with front line chemotherapy (CT) is a standard treatment but some concern raised about tolerance of bevacizumab for these patients. The purpose of PRODIGE 20 was to evaluate tolerance and efficacy of bevacizumab according to specific end points in this population. Patients and methods: Patients aged 75 years and over were randomly assigned to bevacizumab + CT (BEV) versus CT. LV5FU2, FOLFOX and FOLFIRI regimen were prescribed according to investigator's choice. The composite co-primary end point, assessed 4 months after randomization, was based on efficacy (tumor control and absence of decrease of the Spitzer QoL index) and safety (absence of severe cardiovascular toxicities and unexpected hospitalization). For each arm, the treatment will be consider as inefficient if 20% or less of the patients met the efficacy criteria and not safe if 40% or less met the safety criteria. Results: About 102 patients were randomized (51 BEV and 51 CT), median age was 80 years (range 75-91). Primary end point was met for efficacy in 50% and 58% and for safety in 61% and 71% of patients in BEV and CT, respectively. Median progression-free survival was 9.7 months in BEV and 7.8 months in CT. Median overall survival was 21.7 months in BEV and 19.8 months in CT. The 36-month overall survival rate was 27% in BEV and 10.1% in CT. Severe toxicities grade 3/4 were mainly non-hematologic toxicities (80.4% in BEV, 63.3% in CT). Conclusion: Bevacizumab combined with CT was safe and efficient. Both arms met the primary safety and efficacy criteria.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colorectal Neoplasms/drug therapy , Age Factors , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Bevacizumab/administration & dosage , Camptothecin/administration & dosage , Camptothecin/analogs & derivatives , Colorectal Neoplasms/pathology , Female , Fluorouracil/administration & dosage , Humans , Leucovorin/administration & dosage , Male , Neoplasm Metastasis , Organoplatinum Compounds/administration & dosage , Survival Rate
2.
Ann Oncol ; 27(1): 121-7, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26487578

ABSTRACT

BACKGROUND: Metastatic colorectal cancer (mCRC) frequently occurs in elderly patients. However, data from a geriatric tailored randomized trial about tolerance to and the efficacy of doublet chemotherapy (CT) with irinotecan in the elderly are lacking. The benefit of first-line CT intensification remains an issue in elderly patients. PATIENTS AND METHODS: Elderly patients (75+) with previously untreated mCRC were randomly assigned in a 2 × 2 factorial design (four arms) to receive 5-FU (5-fluorouracil)-based CT, either alone (FU: LV5FU2 or simplified LV5FU2) or in combination with irinotecan [IRI: LV5FU2-irinotecan or simplified LV5FU2-irinotecan (FOLFIRI)]. The CLASSIC arm was defined as LV5FU2 or LV5FU2-irinotecan and the SIMPLIFIED arm as simplified LV5FU2 or FOLFIRI. The primary end point was progression-free survival (PFS). Secondary end points were overall survival (OS), safety and objective response rate (ORR). RESULTS: From June 2003 to May 2010, 71 patients were randomly assigned to LV5FU2, 71 to simplified LV5FU2, 70 to LV5FU2-irinotecan and 70 to FOLFIRI. The median age was 80 years (range 75-92 years). No significant difference was observed for the median PFS: FU 5.2 months versus IRI 7.3 months, hazard ratio (HR) = 0.84 (0.66-1.07), P = 0.15 and CLASSIC 6.5 months versus SIMPLIFIED 6.0 months, HR = 0.85 (0.67-1.09), P = 0.19. The ORR was superior in IRI (P = 0.0003): FU 21.1% versus IRI 41.7% and in CLASSIC (P = 0.04): CLASSIC 37.1% versus SIMPLIFIED 25.6%. Median OS was 14.2 months in FU versus 13.3 months in IRI, HR = 0.96 (0.75-1.24) and 15.2 months in CLASSIC versus 11.4 months in SIMPLIFIED, HR = 0.71 (0.55-0.92). More patients presented grade 3-4 toxicities in IRI (52.2% versus 76.3%). CONCLUSION: In this elderly population, adding irinotecan to an infusional 5-FU-based CT did not significantly increase either PFS or OS. Classic LV5FU2 was associated with an improved OS compared with simplified LV5FU2. CLINICALTRIALSGOV: NCT00303771.


Subject(s)
Adenocarcinoma/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colorectal Neoplasms/drug therapy , Adenocarcinoma/mortality , Adenocarcinoma/secondary , Aged , Aged, 80 and over , Camptothecin/administration & dosage , Camptothecin/analogs & derivatives , Colorectal Neoplasms/mortality , Colorectal Neoplasms/pathology , Female , Fluorouracil/administration & dosage , Humans , Irinotecan , Leucovorin/administration & dosage , Male , Multivariate Analysis , Proportional Hazards Models , Treatment Outcome
3.
Eur J Pain ; 28(3): 491-501, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37965922

ABSTRACT

BACKGROUND: Placebo use is widespread in clinical practice. However, they are most often administered deceptively rather than openly. It is often suggested that open-label placebos (OLP) are less effective than deceptive placebos (DP). This study aimed to compare the use of DP and OLP treatments to reduce pain in healthy volunteers. METHODS: We conducted a non-inferiority, parallel, randomized, controlled trial, which also included a nested cross-over no-treatment condition. This study was conducted at a university clinic in France. RESULTS: We included 60 subjects and the main result shows that the OLP was not inferior to the DP by a margin of 10 mm. The mean difference between both groups regarding intensity of pain was 0.7 mm with a 95% compatibility interval (95% CI) of ]-∞; 5.4], and 97.5% CI of ]-∞; 6.3]. Secondary outcomes require cautious interpretation of the effect of placebo versus no treatment due to a time-treatment interaction. CONCLUSION: The study indicates that OLP may perform just as well as DP and could provide support for the use of OLP as an ethical alternative to DP when they are to be used in a clinical setting. If only patients knew about the placebo nature of some treatments they are receiving, unnecessary lies could be avoided while maintaining similar placebo effects. SIGNIFICANCE: This study is the first to show non-inferiority of placebos administered honestly, also called OLP, compared to DP in reducing pain. This suggests that OLP could be as effective as their deceptive counterparts while having the ethical advantage of not being required to lie. If deception is not a necessary condition for efficacy, OLP should be preferred over DP.


Subject(s)
Pain , Research Design , Humans , France , Healthy Volunteers , Pain/drug therapy , Placebo Effect
4.
Dig Liver Dis ; 56(9): 1605-1613, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38403514

ABSTRACT

BACKGROUND: Prior trials validated triplet chemotherapy (Tri-CT) with bevacizumab as first line treatment for metastatic colorectal cancer (mCRC) but real-world data are scarce and practices remain heterogeneous. AIMS: To evaluate Tri-CT +/- bevacizumab efficacy and safety, and to identify factors influencing treatment decisions. METHODS: The COLOTRIP retrospective study enrolled mCRC patients treated from 2014 to 2019 in 14 French centers. RESULTS: Of 299 patients (81% PS 0-1, 58% RAS-mutated and 19% BRAF-mutated), 51% received Tri-CT and 49% Tri-CT + bevacizumab. Metastatic disease was classified as resectable (6.5%), potentially resectable (40%), and unresectable (54%). Bevacizumab use was associated with primary tumor location, mutational status and number of metastases. Median overall survival was 33.5 months in the Tri-CT group and 23.9 months in the Tri-CT + bevacizumab group, with median progression-free survival being 14.5 and 11.4 months. After adjusting for initial characteristics, no difference in survival was noted. Around 30% of patients experienced grade ≥3 adverse events. CONCLUSIONS: This study highlights several factors influencing Tri-CT use +/- bevacizumab decision and confirms the real-world good oncological outcomes and tolerability of these regimens in mCRC patients. Our results suggest that Tri-CT alone may by an appropriate option for specific subgroups of patients.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Bevacizumab , Colorectal Neoplasms , Humans , Bevacizumab/administration & dosage , Bevacizumab/therapeutic use , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/pathology , Colorectal Neoplasms/genetics , Colorectal Neoplasms/mortality , Male , Female , Retrospective Studies , Aged , Middle Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , France , Antineoplastic Agents, Immunological/therapeutic use , Antineoplastic Agents, Immunological/administration & dosage , Progression-Free Survival , Adult , Aged, 80 and over
5.
Dig Liver Dis ; 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38981787

ABSTRACT

BACKGROUND: Anti-TNF are usually maintained during pregnancy in patients with inflammatory bowel disease (IBD) but safety is still a concern for them. AIMS: To provide data on management of anti-TNF agents during pregnancy, safety of live vaccines (BCG-MMR-rotavirus) and breastfeeding in newborns and dedicated information delivered to IBD women. METHODS: We performed an observational study in 25 centers from 2016 to 2018. We administered questionnaires to women with IBD receiving anti-TNF during pregnancy with newborn follow-up ≥ one year. RESULTS: Of 153 patients, 52 % maintained anti-TNF during the third trimester. Anti-TNF was shortly resumed in 79 % (58/73) after delivery. The rate of breastfeeding was 44 % (68/153) without any complication; 38 % of the mothers denied to breastfeed based on physician's advice. 26 % (34/129) of the newborns received live vaccines before 6 months-old (BCG:30 %; MMR:63 %; Rotavirus:8 %) and only 3 complications occurred (local BCGitis=1, fever=2). Information concerning anti-TNF during pregnancy/post-partum was delivered to 92 % of the patients, mainly by a gastroenterologist (97 %) who discussed with the obstetrician or the paediatrician in only 48 % and 25 %. CONCLUSION: In IBD patients, maintaining anti-TNF during pregnancy and breastfeeding is safe. Accidental live vaccines before 6 months did not lead to significant adverse events. The communication about these questions remains to improve.

6.
Br J Cancer ; 109(4): 1013-22, 2013 Aug 20.
Article in English | MEDLINE | ID: mdl-23868006

ABSTRACT

BACKGROUND: The aim of our study was to evaluate the prognostic role of immunological microenvironnement in stage II-III CRC patients. METHODS: We constructed a tissue microarray from 196 consecutive patients with stage II-III CRC and compared CD3, CD4, CD8, CD57, CD68, CXCL9/MIG, CXCL13, and PPARγ immunoreactivity in tumour samples and their matched non-tumour tissue. We assessed their association with relapse-free survival (RFS; primary endpoint) and overall survival (OS) in multivariate Cox models. RESULTS: Low densities of CD57+ and CD68+ tumour-infiltrating cells (TIC) independently predicted worse outcomes. A prognostic score combining CD57 (+, > vs -, ≤2 cells per spot) and CD68 (+, >0 vs -, =0 cells per spot) TIC density discriminated CRC patients at low (CD68+/CD57+), intermediate (CD68+/CD57-), or high (CD68-/CD57-) risk, with hazard ratios for the intermediate-risk and high-risk groups of 2.7 (95% confidence interval (CI): 1.3-5.8) and 9.0 (3.2-25.4) for RFS, and 2.5 (1.2-5.1) and 10.6 (3.8-29.2) for OS, respectively, as compared with the low-risk group. Corresponding 5-year survival rates (95% CI) in the low-, moderate- and high-risk groups were 84% (71-91), 65% (54-74), and 12% (2-47), respectively, for RFS, and 91% (80-96), 76% (66-84), and 25% (7-59), respectively, for OS. CONCLUSION: Tumour CD57+ and CD68+ TIC density assessment independently predicts survival in patients with stage II-III CRC. If validated, our score based on a quick, inexpensive, and well-established method such as point counting on diagnostic tissue sections could be used routinely as a prognostic tool in CRC patients.


Subject(s)
Adenocarcinoma/immunology , Antigens, CD/immunology , Antigens, Differentiation, Myelomonocytic/immunology , CD57 Antigens/immunology , Colorectal Neoplasms/immunology , Lymphocytes, Tumor-Infiltrating/immunology , Macrophages/immunology , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Adult , Aged , Aged, 80 and over , Biomarkers , CD3 Complex/immunology , CD4 Antigens/immunology , CD8 Antigens/immunology , Cell Count , Chemokine CXCL13/immunology , Chemokine CXCL9/immunology , Colorectal Neoplasms/mortality , Colorectal Neoplasms/pathology , Female , Humans , Male , Middle Aged , Neoplasm Staging , PPAR gamma/immunology , Prognosis , Proportional Hazards Models
7.
Br J Cancer ; 109(12): 3057-66, 2013 Dec 10.
Article in English | MEDLINE | ID: mdl-24196786

ABSTRACT

BACKGROUND: Small bowel adenocarcinoma (SBA) is a rare tumour with a poor prognosis. Molecular biology data on SBA carcinogenesis are lacking. METHODS: Expression of HER2, ß-catenin, p53 and mismatch repair (MMR) protein was assessed by immunohistochemistry. KRAS, V600E BRAF mutations and microsatellite instability were investigated. RESULTS: We obtained samples from 63 SBA patients (tumour stages: I-II: 30%; III: 35%; IV: 32%; locally advanced: 3%). HER2 overexpression (3+) was observed in 2 out of 62 patients, overexpression of p53 in 26 out of 62, abnormal expression of ß-catenin in 12 out of 61, KRAS mutation in 21 out of 49, BRAF V600E mutation in 1 out of 40 patients, MMR deficiency (dMMR) in 14 out of 61 and was consistent with Lynch syndrome in 9 out of 14 patients. All of the dMMR tumours were in the duodenum or jejunum and only one was stage IV. Median overall survival (OS) was 36.6 months (95% CI, 26.9-72.2). For all patients, in univariate analysis, stages I-II (P<0.001), WHO PS 0-1 (P=0.01) and dMMR phenotype (P=0.02) were significantly associated with longer OS. In multivariate analysis, disease stage (P=0.01) and WHO PS 0-1 (P=0.001) independently predicted longer OS. For stage IV patients, median OS was 20.5 months (95% CI: 14.6; 36.6 months). In multivariate analysis, WHO PS 0-1 (P=0.0001) and mutated KRAS status (P=0.02) independently predicted longer OS. CONCLUSION: This large study suggests that molecular alterations in SBA are closer to those in colorectal cancer (CRC) than those in gastric cancer, with low levels of HER 2 overexpression and high frequencies of KRAS mutations. The seemingly higher frequency of dMMR than in CRC may be explained by the higher frequency of Lynch syndrome in SBA patients. A dMMR phenotype was significantly associated with a non-metastatic tumour (P=0.02). A trend for a good prognosis and a duodenum or jejunum primary site was associated with dMMR.


Subject(s)
Adenocarcinoma/genetics , Adenocarcinoma/pathology , Intestinal Neoplasms/genetics , Intestinal Neoplasms/pathology , Adenocarcinoma/drug therapy , Adenocarcinoma/metabolism , Adult , Aged , Female , Humans , Immunohistochemistry , Intestinal Neoplasms/drug therapy , Intestinal Neoplasms/metabolism , Male , Microsatellite Instability , Middle Aged , Phenotype , Prognosis , Survival Analysis
9.
Nutr Cancer ; 64(4): 535-42, 2012.
Article in English | MEDLINE | ID: mdl-22494155

ABSTRACT

Although malnutrition is known to be frequent in cancer patients, it has not been described in a selected population of patients with gastrointestinal malignancies under chemotherapy only. Physician judgment about malnutrition and risk factors for malnutrition were also evaluated. All consecutive in- and outpatients of 11 centers were prospectively enrolled in a cross-sectional 14-day period study and classified according to the French health recommendations [Haute Autorité de Santé (HAS)]. Among 313 patients enrolled in 11 centers (mean age = 63 yr; range = 21-93; 67% male) mainly with colorectal (58%), pancreatic (15%), gastric (11%), and hepatobiliary (10%) primary tumors, the prevalence of malnutrition was 52%. Moderate and severe malnutrition was present in 27% and 25% of cases, respectively. Physicians considered it in 36% and 6% of cases, respectively, thereby misclassifying 134 patients (43%). The agreement between the HAS definition and the physicians' judgment was very low (κ = 0.30). Most of the patients who were identified as severely malnourished received no nutritional support. Performance status and pancreatic and gastric cancers were independently associated with malnutrition. Malnutrition levels are high, around 50%, unequally distributed according to the primitive tumor. It is still underestimated by physicians. Weight loss remains a clinically relevant, simple, and reliable marker of malnutrition.


Subject(s)
Gastrointestinal Neoplasms/epidemiology , Malnutrition/epidemiology , Nutritional Status , Adult , Aged , Aged, 80 and over , Cross-Sectional Studies , Female , Gastrointestinal Neoplasms/physiopathology , Humans , Logistic Models , Male , Middle Aged , Multivariate Analysis , Nutrition Assessment , Nutritional Support/methods , Outpatients , Prevalence , Prospective Studies , Risk Factors , Weight Loss , Young Adult
10.
Water Sci Technol ; 65(5): 789-94, 2012.
Article in English | MEDLINE | ID: mdl-22339011

ABSTRACT

Fuel cells on wastewater treatment plants are a relatively new technology to convert biogas from anaerobic digestion into thermal and electrical energy. Since the end of 2007, a type of MCFC fuel cell (>250 kW(el), 180 kW(th)) has been installed at Stuttgart-Möhringen wastewater treatment plant. The goals of this research project are to raise the power self-sufficiency in Stuttgart-Möhringen, to further optimise high temperature fuel cells using biogas and to gain practical experience. After approximately 9,000 h of operation, a mean electrical 'gross'-efficiency of 44% was achieved. To fully exploit this high electrical efficiency, it is essential to keep the energy consumption of peripheral devices (gas pressure unit, gas cleaning unit, etc.) of the fuel cell as low as possible.


Subject(s)
Bioelectric Energy Sources , Carbonates/chemistry , Waste Disposal, Fluid/instrumentation , Water Purification/instrumentation , Electricity , Electrodes , Germany
11.
Ann Oncol ; 21(9): 1786-1793, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20223786

ABSTRACT

BACKGROUND: Small-bowel adenocarcinoma (SBA) is a rare tumor of poor prognosis. Data on the efficacy of chemotherapy for advanced SBA are scarce. PATIENTS AND METHODS: All patients with advanced SBA who received frontline chemotherapy from 1996 to 2008 were eligible for this retrospective multicenter study. RESULTS: Ninety-three consecutive patients were included. In the entire population, the median progression-free survival (PFS) and overall survival (OS) times were 6.6 and 15.1 months, respectively. Median PFS times among patients treated with LV5FU2 (n = 10), FOLFOX (n = 48), FOLFIRI (n = 19) and LV5FU2-cisplatin (n = 16) were 7.7, 6.9, 6.0 and 4.8 months, respectively, while median OS times were 13.5, 17.8, 10.6 and 9.3 months, respectively. In multivariate analysis, World Health Organization performance status (PS) (P < 0.0001) and elevated serum levels of carcinoembryonic antigen (CEA) (P = 0.02) and carbohydrate antigen 19-9 (CA 19-9) (P = 0.03) were the only variables significantly associated with poor OS. In the subgroup of patients treated with platinum-based chemotherapy, multivariate analysis showed that LV5FU2-cisplatin was associated with poorer PFS (P < 0.0001) and OS (P = 0.02) compared with FOLFOX. CONCLUSIONS: This is the largest study of chemotherapy in advanced SBA. Baseline PS and CEA and CA 19-9 levels were the main prognostic factors. FOLFOX seems to be the most effective platinum-based chemotherapy regimen.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Duodenal Neoplasms/drug therapy , Ileal Neoplasms/drug therapy , Jejunal Neoplasms/drug therapy , Liver Neoplasms/drug therapy , Lung Neoplasms/drug therapy , Peritoneal Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Camptothecin/administration & dosage , Camptothecin/analogs & derivatives , Cisplatin/administration & dosage , Duodenal Neoplasms/pathology , Female , Fluorouracil/administration & dosage , Follow-Up Studies , Humans , Ileal Neoplasms/pathology , Intestine, Small/drug effects , Intestine, Small/pathology , Irinotecan , Jejunal Neoplasms/pathology , Leucovorin/administration & dosage , Liver Neoplasms/secondary , Lung Neoplasms/secondary , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Staging , Organoplatinum Compounds/administration & dosage , Oxaliplatin , Peritoneal Neoplasms/secondary , Prognosis , Retrospective Studies , Survival Rate
12.
Digit Health ; 6: 2055207620968355, 2020.
Article in English | MEDLINE | ID: mdl-33194219

ABSTRACT

BACKGROUND: The potential for machine learning to disrupt the medical profession is the subject of ongoing debate within biomedical informatics. OBJECTIVE: This study aimed to explore psychiatrists' opinions about the potential impact innovations in artificial intelligence and machine learning on psychiatric practice. METHODS: In Spring 2019, we conducted a web-based survey of 791 psychiatrists from 22 countries worldwide. The survey measured opinions about the likelihood future technology would fully replace physicians in performing ten key psychiatric tasks. This study involved qualitative descriptive analysis of written responses ("comments") to three open-ended questions in the survey. RESULTS: Comments were classified into four major categories in relation to the impact of future technology on: (1) patient-psychiatrist interactions; (2) the quality of patient medical care; (3) the profession of psychiatry; and (4) health systems. Overwhelmingly, psychiatrists were skeptical that technology could replace human empathy. Many predicted that 'man and machine' would increasingly collaborate in undertaking clinical decisions, with mixed opinions about the benefits and harms of such an arrangement. Participants were optimistic that technology might improve efficiencies and access to care, and reduce costs. Ethical and regulatory considerations received limited attention. CONCLUSIONS: This study presents timely information on psychiatrists' views about the scope of artificial intelligence and machine learning on psychiatric practice. Psychiatrists expressed divergent views about the value and impact of future technology with worrying omissions about practice guidelines, and ethical and regulatory issues.

13.
Rev Mal Respir ; 36(6): 649-663, 2019 Jun.
Article in French | MEDLINE | ID: mdl-31204231

ABSTRACT

INTRODUCTION: The benefit of tyrosine kinase inhibitors for patients with an EGFR wild-type non-small cell lung cancer (NSCLC) remains controversial. METHODS: The survival of patients with an EGFR wild-type NSCLC who received second- or third-line erlotinib treatment was assessed using real-life data that had been collected in a prospective, national, multicenter, non-interventional cohort study. RESULTS: Data from 274 patients were analysed, 185 (68%) treated with erlotinib and 89 (32%) treated with supportive care only. The median overall survival was 4.2months (95% CI [3.5; 5.4]) with erlotinib, and 1.3months (95% CI [1.0; 1.8]) with supportive care. Survival rate at 3, 6, and 12months was 62%, 37%, and 17%, respectively, with erlotinib, versus 20%, 8%, et 3%, with exclusive supportive care. Significant predictive factors for longer overall survival were the presence of adenocarcinoma, and use of 1st line chemotherapy including either taxanes, pemetrexed or vinorelbine (P<0.05). CONCLUSION: Erlotinib remains a valuable therapeutic option to treat inoperable locally advanced or metastatic NSCLC after failure of at least one prior chemotherapy regimen in fragile patients who are not eligible for chemotherapy.


Subject(s)
Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/mortality , Erlotinib Hydrochloride/therapeutic use , Lung Neoplasms/drug therapy , Lung Neoplasms/mortality , Protein Kinase Inhibitors/therapeutic use , Adult , Aged , Aged, 80 and over , Carcinoma, Non-Small-Cell Lung/genetics , ErbB Receptors/genetics , Female , Humans , Lung Neoplasms/genetics , Male , Middle Aged , Prospective Studies , Survival Rate
14.
Eur J Cancer ; 97: 16-24, 2018 07.
Article in English | MEDLINE | ID: mdl-29777975

ABSTRACT

BACKGROUND: Older patients have frailty characteristics that impair the transposition of treatment results found in younger patients. Predictive factors are needed to help with treatment choices for older patients. The PRODIGE 20 study is a randomized phase II study that evaluated chemotherapy associated with bevacizumab (BEV) or not (CT) in patients aged 75 years or older. PATIENTS AND METHODS: Patients underwent a geriatric assessment at randomization and at each evaluation. The predictive value of geriatric and oncologic factors was determined for the primary composite end-point assessing safety and efficacy of treatment (BEV or CT) simultaneously and also progression-free survival (PFS) and overall survival (OS). RESULTS: 102 patients were randomized (51 BEV and 51 CT; median age 80 years [range 75-91]). On multivariate analysis, baseline normal independent activity of daily living (IADL) score and no previous cardiovascular disease predicted the primary end-point. High (versus low) baseline Köhne score predicted short PFS and baseline Spitzer quality of life (QoL) score <8, albumin level ≤35 g/L, CA19.9 >2 LN levels above normal and high baseline Köhne score predicted short OS. Survival without deteriorated QoL and autonomy was similar with BEV and CT. On subgroup analyses, the benefit of bevacizumab seemed to be maintained in patients with baseline impaired IADL or nutritional status. CONCLUSION: Normal IADL score was associated with a good efficacy and safety of both BEV and CT. Köhne criteria may be relevant prognostic factors in older patients. Adding bevacizumab to chemotherapy does not impair patient autonomy or QoL.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colorectal Neoplasms/drug therapy , Neoplasm Recurrence, Local/drug therapy , Aged , Aged, 80 and over , Bevacizumab/administration & dosage , Camptothecin/administration & dosage , Colorectal Neoplasms/pathology , Female , Fluorouracil/administration & dosage , Follow-Up Studies , Humans , Irinotecan/administration & dosage , Leucovorin/administration & dosage , Male , Neoplasm Metastasis , Neoplasm Recurrence, Local/pathology , Prognosis , Survival Rate
15.
Rev Mal Respir ; 34(9): 991-999, 2017 Nov.
Article in French | MEDLINE | ID: mdl-29111174

ABSTRACT

INTRODUCTION: The objective of the ESCAP-2011-CPHG cohort study was to perform a real-life analysis of therapeutic strategies used during the first 2years of follow-up after a diagnosis of primary lung cancer. This paper presents the study and its first results in non-small-cell lung cancer (NSCLC). METHODS: Pulmonologists in the respiratory disease departments of 53 general hospitals consecutively included all patients aged 18years and over with lung cancer newly diagnosed in 2010. RESULTS: Of the 3943 patients included, 3418 (mean age: 65.4 years; male: 76%; never smokers: 12%) had NSCLC (adenocarcinoma: 53%; stages 0-II, IIIA, IIIB and IV: 18, 14, 9 and 59%, respectively). Mean follow-up was 13.2 (SD: 10.1) months; mean number of strategies implemented was 2 (SD: 1.3). Overall, 62% of patients had chemotherapy in the first strategy (74% in the second strategy); the rate of chemotherapy alone increased from 6 to 56% with cancer stage. CONCLUSIONS: ESCAP-2011-CPHG opens the way to many possible analyses of the therapeutic strategies currently implemented in French hospitals, comparing strategies, survival or patient characteristics.


Subject(s)
Carcinoma, Non-Small-Cell Lung/epidemiology , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/therapy , Lung Neoplasms/epidemiology , Lung Neoplasms/pathology , Lung Neoplasms/therapy , Neoadjuvant Therapy , Practice Patterns, Physicians'/statistics & numerical data , Adult , Aged , Aged, 80 and over , Carcinoma, Non-Small-Cell Lung/diagnosis , Cohort Studies , Female , France/epidemiology , Hospitals, General/statistics & numerical data , Humans , Lung Neoplasms/diagnosis , Male , Middle Aged , Neoadjuvant Therapy/methods , Neoadjuvant Therapy/statistics & numerical data , Neoplasm Staging , Smoking , Time Factors
16.
Rev Mal Respir ; 23(3 Pt 1): 273-6, 2006 Jun.
Article in French | MEDLINE | ID: mdl-16788529

ABSTRACT

INTRODUCTION: Intestinal metastasis from primary lung cancers is rare and usually asymptomatic. CASE REPORT: We report two cases of symptomatic small bowel metastasis. The first one presented with a persistent anaemia occurring in a 54 year old man who had undergone a left lower lobectomy for a large cell carcinoma. The second case was a 75 year old man who presented with peritonitis which led to discovery of a lung primary. CONCLUSION: Intestinal metastasis can be the presenting feature of, or complicate lung cancer. Symptomatology depends on metastasis localisation. Their treatment is difficult and they are associated with a poor prognosis.


Subject(s)
Intestinal Neoplasms/secondary , Intestine, Small/pathology , Lung Neoplasms/pathology , Aged , Humans , Intestinal Neoplasms/diagnosis , Male , Middle Aged
17.
Rev Mal Respir ; 23(5 Pt 1): 497-502, 2006 Nov.
Article in French | MEDLINE | ID: mdl-17314755

ABSTRACT

BACKGROUND: Bone metastases are common in lung cancer and are leading to increasing consumption of health care resources. The therapeutic choice for the clinician is extensive, from biphosphonates to percutaneous vertebroplasty. In the absence of official guidelines the management varies from centre to centre. There are very few economic analyses of these patients. METHODS: Study 06-01 of the French Lung Oncology Group is a medico-economic analysis of the management of bone metastases in lung cancer. It is a national, multicentre, observational, epidemiological study. The primary objective is to assess the epidemiology, the management strategies and the costs of bone metastases in lung cancer. The secondary objective is to develop a medico-economic model of the management based on a Markov model in order to evaluate the effectiveness of different therapeutic strategies. EXPECTED RESULTS: The aim of this study is a better understanding of theses patients at a time when few observational studies have been undertaken.


Subject(s)
Bone Neoplasms/economics , Bone Neoplasms/therapy , Health Care Costs , Lung Neoplasms/economics , Lung Neoplasms/therapy , Adolescent , Adult , Aged , Aged, 80 and over , Bone Neoplasms/epidemiology , Bone Neoplasms/secondary , Cost-Benefit Analysis , France/epidemiology , Health Care Costs/statistics & numerical data , Humans , Incidence , Lung Neoplasms/epidemiology , Lung Neoplasms/pathology , Markov Chains , Middle Aged
18.
Biochim Biophys Acta ; 1160(3): 275-80, 1992 Dec 28.
Article in English | MEDLINE | ID: mdl-1477099

ABSTRACT

During the characterization of malaria vaccine candidate proteins, three metalloproteinases having a molecular mass of 220, 95 and 70 kDa were found to be co-isolated with the rhoptry-associated protein-1 (RAP-1) complex, but not with RAP-3 or gp195. These enzymes were also found in detergent extracts of saponin-lysed Plasmodium falciparum. Of nine proteinase inhibitors tested, only EDTA was found to abrogate activity. Dose-dependent curves were determined for several metal ions and cobalt was found to synergistically enhance enzyme activity. The gelatinases were immunoprecipitated with monospecific polyclonal antisera to macrophage and fibroblast gelatinase; however, these sera did not react with intracellular parasites by indirect immunofluorescence. These results indicate that the matrix metalloproteinases co-isolated with RAP-1 originate from human serum used to cultivate P. falciparum in vitro.


Subject(s)
Metalloendopeptidases/metabolism , Plasmodium falciparum/metabolism , Protozoan Proteins/isolation & purification , Protozoan Proteins/metabolism , Animals , Calcium/pharmacology , Cobalt/pharmacology , Collagenases/isolation & purification , Enzyme Activation/drug effects , Matrix Metalloproteinase 2 , Matrix Metalloproteinase 9 , Metalloendopeptidases/isolation & purification
20.
Presse Med ; 34(19 Pt 1): 1373-4, 2005 Nov 05.
Article in French | MEDLINE | ID: mdl-16292190

ABSTRACT

INTRODUCTION: This is the first reported case of a histologically-proved mediastinal metastatic site of a transitional cell carcinoma of the bladder. CASE: A 61-year-old woman who had undergone a total cystectomy 3 years earlier for transitional cell carcinoma was hospitalized for dysphagia. Endoscopy showed impassable stenosis beginning 25 cm below the dental arch, without any developing endoluminal lesion. Histologic analysis of the biopsy samples identified transitional cell carcinoma infiltration of the muscularis and deep mucosa of the esophagus. DISCUSSION: Three years after a diagnosis of bladder cancer, invasion of the paraesophageal lymph nodes was accompanied by infiltration of the esophageal muscularis and contiguous mucosa. Esophageal stenoses by carcinomatous mediastinitis are rare; when they occur, it is usually secondary to breast cancer. They are generally treated endoscopically, which entails a risk of perforation.


Subject(s)
Carcinoma, Transitional Cell/pathology , Mediastinal Neoplasms/secondary , Mediastinitis/etiology , Urinary Bladder Neoplasms/pathology , Esophageal Stenosis/etiology , Female , Humans , Mediastinal Neoplasms/diagnosis , Middle Aged
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