Menopausal symptoms in epithelial ovarian cancer survivors: a GINECO VIVROVAIRE2 study.

OBJECTIVE: We have previously shown that epithelial ovarian cancer (EOC) and its treatments have negative effects on long-term quality of life (QoL) and fatigue. The present multicenter study investigated the main menopausal symptoms and gynecological management of EOC survivors (EOCS). METHODS: 166 patients with relapse-free ≥3 years after the end of treatment attended a consultation with a gynecologist, including a questionnaire related to vasomotor symptoms (VMS) and sexuality, a clinical examination, a blood sample and an osteodensitometry. QoL, fatigue, insomnia and mood disorders were measured with validated questionnaires and correlated to VMS. VMS and QoL were assessed according to natural menopause (NM) or surgical menopause (SM). RESULTS: Mean age at the survey was 62 [21-83] years and stage III/IV (48%). Mean delay since the end of treatment was 6 years. Fifty-nine patients (36%) had SM. Half of patients reported VMS. Seventy-two percent of EOCS with SM had VMS compared to 41% with NM (P < .001). VMS were not associated with poor global QoL, fatigue, insomnia or mood disorders. Two-thirds of EOCS reported a decrease in libido. Patients with SM showed a greater decrease in libido than NM (P < .02). Fourteen percent of them had osteoporosis and 50% osteopenia. Among the 85 patients with VMS, 80 did not receive HRT after cancer treatment. At the time of the survey, only 7 (4%) patients were receiving hormone replacement therapy (HRT). CONCLUSIONS: VMS and sexual disorders are frequently reported by EOCS, particularly among patients with SM. Most EOCS with menopausal symptoms could benefit from HRT to improve these symptoms.

Long-term safety in patients with recurrent ovarian cancer treated with niraparib versus placebo: Results from the phase III ENGOT-OV16/NOVA trial.

OBJECTIVE: Niraparib is a poly(ADP-ribose) polymerase (PARP) inhibitor approved for use in heavily pretreated patients and as maintenance treatment in patients with newly-diagnosed or recurrent ovarian cancer following a response to platinum-based chemotherapy. We present long-term safety data for niraparib from the ENGOT-OV16/NOVA trial. METHODS: This multicenter, double-blind, randomized, controlled phase III trial evaluated the efficacy and safety of niraparib for the treatment of recurrent ovarian cancer. Patients were randomly assigned 2:1 to receive either once-daily niraparib 300 mg or placebo. Two independent cohorts were enrolled based on germline BRCA mutation status. The primary endpoint was progression-free survival, reported previously. Long-term safety data were from the most recent data cutoff (September 2017). RESULTS: Overall, 367 patients received niraparib 300 mg once daily. Dose reductions due to TEAEs were highest in month 1 (34%) and declined every month thereafter. Incidence of any-grade and grade ≥ 3 hematologic and symptomatic TEAEs was also highest in month 1 and subsequently declined. Incidence of grade ≥ 3 thrombocytopenia decreased from 28% (month 1) to 9% and 5% (months 2 and 3, respectively), with protocol-directed dose interruptions and/or reductions. Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) were reported in 2 and 6 niraparib-treated patients, respectively, and in 1 placebo patient each. Treatment discontinuations due to TEAEs were <5% in each month and time interval measured. CONCLUSION: These data demonstrate the importance of appropriate dose reduction according to toxicity criteria and support the safe long-term use of niraparib for maintenance treatment in patients with recurrent ovarian cancer. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01847274.

Need for risk-adapted therapy for malignant ovarian germ cell tumors: A large multicenter analysis of germ cell tumors' patients from French TMRG network.

BACKGROUND: Malignant ovarian germ cell tumors are rare tumors, affecting young women with a generally favorable prognosis. The French reference network for Rare Malignant Gynecological Tumors (TMRG) aims to improve their management. The purpose of this study is to report clinicopathological features and long-term outcomes, to explore prognostic parameters and to help in considering adjuvant strategy for stage I patients. PATIENTS AND METHODS: Data from patients with MOGCT registered among 13 of the largest centers of the TMRG network were analyzed. We report clinicopathological features, estimated 5-year event-free survival (5y-EFS) and 5-year overall survival (5y-OS) of MOGCT patients. RESULTS: We collected data from 147 patients including 101 (68.7%) FIGO stage I patients. Histology identifies 40 dysgerminomas, 52 immature teratomas, 32 yolk sac tumors, 2 choriocarcinomas and 21 mixed tumors. Surgery was performed in 140 (95.2%) patients and 106 (72.1%) received first line chemotherapy. Twenty-two stage I patients did not receive chemotherapy. Relapse occurred in 24 patients: 13 were exclusively treated with upfront surgery and 11 received surgery and chemotherapy. 5y-EFS was 82% and 5y-OS was 92.4%. Stage I patients who underwent surgery alone had an estimated 5y-EFS of 54.6% and patients receiving adjuvant chemotherapy 94.4% (P < .001). However, no impact on estimated 5y-OS was observed: 96.3% versus 97.8% respectively (P = .62). FIGO stage, complete primary surgery and post-operative alpha fetoprotein level significantly correlated with survival. CONCLUSION: Adjuvant chemotherapy does not seem to improve survival in stage I patients. Active surveillance can be proposed for selected patients with a complete surgical staging.

Long-term fatigue and quality of life among epithelial ovarian cancer survivors: a GINECO case/control VIVROVAIRE I study.

BACKGROUND: Few data are available on long-term fatigue (LTF) and quality of life (QoL) among epithelial ovarian cancer survivors (EOCS). In this case-control study, we compared LTF, symptoms and several QoL domains in EOCS relapse-free ≥3 years after first-line treatment and age-matched healthy women. PATIENTS AND METHODS: EOCS were recruited from 25 cooperative GINECO centers in France. Controls were randomly selected from the electoral rolls. All participants completed validated self-reported questionnaires: fatigue (FACIT-F), QoL (FACT-G/O), neurotoxicity (FACT-Ntx), anxiety/depression (HADS), sleep disturbance (ISI), and physical activity (IPAQ). Severe LTF (SLTF) was defined as a FACIT-F score <37/52. Univariate and multivariate logistic regressions were conducted to analyze SLTF and its influencing factors in EOCS. RESULTS: A total of 318 EOCS and 318 controls were included. EOCS were 63-year-old on average, with FIGO stage I/II (50%), III/IV (48%); 99% had received platinum and taxane chemotherapy, with an average 6-year follow-up. There were no differences between the two groups in socio-demographic characteristics and global QoL. EOCS had poorer FACIT-F scores (40 versus 45, P < 0.0001), lower functional well-being scores (18 versus 20, P = 0.0002), poorer FACT-O scores (31 versus 34 P < 0.0001), and poorer FACT-Ntx scores (35 versus 39, P < 0.0001). They also reported more SLTF (26% versus 13%, P = 0.0004), poorer sleep quality (63% versus 47%, P = 0.0003), and more depression (22% versus 13%, P = 0.01). Fewer than 20% of EOCS and controls exercised regularly. In multivariate analyses, EOCS with high levels of depression, neurotoxicity, and sleep disturbance had an increased risk of developing SLTF (P < 0.01). CONCLUSION: Compared with controls, EOCS presented similar QoL but persistent LTF, EOC-related symptoms, neurotoxicity, depression, and sleep disturbance. Depression, neuropathy, and sleep disturbance are the main conditions associated with severe LTF.

Safety and dose modification for patients receiving niraparib.

Background: Niraparib is a poly(ADP-ribose) polymerase inhibitor approved in the USA and Europe for maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy. In the pivotal ENGOT-OV16/NOVA trial, the dose reduction rate due to treatment-emergent adverse event (TEAE) was 68.9%, and the discontinuation rate due to TEAE was 14.7%, including 3.3% due to thrombocytopenia. A retrospective analysis was carried out to identify clinical parameters that predict dose reductions. Patients and methods: All analyses were carried out on the safety population, comprising all patients who received at least one dose of study drug. Patients were analyzed according to the study drug consumed (i.e., as treated). A predictive modeling method (decision trees) was used to identify important variables for predicting the likelihood of developing grade ≥3 thrombocytopenia within 30 days after the first dose of niraparib and determine cut-off points for chosen variables. Results: Following dose modification, 200 mg was the most commonly administered dose in the ENGOT-OV16/NOVA trial. Baseline platelet count and baseline body weight were identified as risk factors for increased incidence of grade ≥3 thrombocytopenia. Patients with a baseline body weight <77 kg or a baseline platelet count <150 000/µl in effect received an average daily dose ∼200 mg (median = 207 mg) due to dose interruption and reduction. Progression-free survival in patients who were dose reduced to either 200 or 100 mg was consistent with that of patients who remained at the 300 mg starting dose. Conclusions: The analysis presented suggests that patients with baseline body weight of <77 kg or baseline platelets of <150 000/µl may benefit from a starting dose of 200 mg/day. ClinicalTrials.gov ID: NCT01847274.

Phase II randomized study of PM01183 versus topotecan in patients with platinum-resistant/refractory advanced ovarian cancer.

BACKGROUND: PM01183 is a new compound that blocks active transcription, produces DNA breaks and apoptosis, and affects the inflammatory microenvironment. PM01183 showed strong antitumor activity in preclinical models of cisplatin-resistant epithelial ovarian cancer. PATIENTS AND METHODS: Patients with platinum-resistant/refractory ovarian cancer were included in a two-stage, controlled, randomized (in a second stage), multicenter, phase II study. Primary endpoint was overall response rate (ORR) by RECIST and/or GCIG criteria. The exploratory first stage (n = 22) confirmed the activity of PM01183 as a single agent at 7.0 mg flat dose every 3 weeks (q3wk). The second stage (n = 59) was randomized and controlled with topotecan on days 1-5 q3wk or weekly (every 4 weeks, q4wk). RESULTS: ORR was 23% (95% CI, 13%-37%) for 52 PM01183-treated patients. Median duration of response was 4.6 months (95% CI, 2.5-6.9 months), and 23% (95% CI, 0%-51%) of responses lasted 6 months or more. Ten of the 12 confirmed responses were reported for 33 patients with platinum-resistant disease [ORR = 30% (95% CI, 16%-49%)]; for the 29 patients treated with topotecan in the second stage, no responses were found. Median PFS for all PM01183-treated patients was 4.0 months (95% CI, 2.7-5.6 months), and 5.0 months (95% CI, 2.7-6.9 months) for patients with platinum-resistant disease. Grade 3/4 neutropenia in 85% of patients; febrile neutropenia in 21% and fatigue (grade 3 in 35%) were the principal safety findings for PM01183. CONCLUSION: PM01183 is an active drug in platinum-resistant/refractory ovarian cancer and warrants further development. The highest activity was observed in platinum-resistant disease. Its safety profile indicates the dose should be adjusted to body surface area (mg/m2). TRIAL CODE: EudraCT 2011-002172-16.

Phase II study of the PI3K inhibitor BKM120 in patients with advanced or recurrent endometrial carcinoma: a stratified type I-type II study from the GINECO group.

Backround:Patients with metastatic endometrial carcinoma have a poor prognosis and PIK3CA mutations and amplifications are common in these cancers. This study evaluated the efficacy and safety of the pure PI3K inhibitor BKM120 in advanced or recurrent endometrial carcinoma. METHODS: This phase II, multicentre, single-arm, double strata (histological low grade (LG) or high grade (HG)) open-label study enrolled patients with histologically confirmed advanced or recurrent endometrial carcinoma who had received not more than one prior chemotherapy regimen. Patients received initially BKM120 100 mg tablets once daily. Primary end points were proportion of patients free of progression at 2 months (HG strata) or at 3 months (LG strata), objective response rate (ORR), and safety. RESULTS: A total of 40 patients were enrolled, of whom 16 patients had received BKM120 at 100 mg. Because of high toxicities (cutaneous rash (54%), depressive events (47%), and anxiety (40%), the IDMC has proposed to stop recruitment at 100 mg and to continue the clinical trial with a lower dose of 60 mg per day. In addition, 24 patients (median age 67 years old) were newly enrolled (14 in the LG strata and 10 in the HG strata). Rate of nonprogression at 2 months in the HG strata was 70% and at 3 months was 60% in the LG strata. Median progression-free survival (PFS) for all patients is 4.5 months (CI 95% 2.8-6.1), and the median PFS for LG strata is 8.3 months compared with 3.8 months for the HG strata. No response was reported. At 60 mg per day, the most commonly reported treatment-related adverse events (AEs) were hyperglycaemia (58%), cognitive (31%), digestive (28%), hepatic liver functions (26%), and rash (23%). The most commonly reported treatment-related grade ⩾3 AEs were HTA (17%), hyperglycaemia (17%), and increased alanine aminotransferase (24%). Five patients (21%) stopped BKM120 for toxicity. CONCLUSIONS: The BKM120 was associated with an unfavourable safety profile and minimal antitumour activity in monotherapy in advanced or recurrent endometrial carcinoma. The clinical trial was stopped before end of recruitment for toxicity.

A phase II study of lenalidomide in platinum-sensitive recurrent ovarian carcinoma.

BACKGROUND: Lenalidomide has dual antiangiogenic and immunomodulatory properties and confirmed antitumor activity in hematologic malignancies. A phase II study investigating the safety and efficacy of continuous lenalidomide in recurrent ovarian cancer patients was initiated. PATIENTS AND METHODS: Patients with histologically confirmed epithelial ovarian, fallopian tube or primary peritoneal carcinoma, with asymptomatic recurrence 6 months after prior therapy were treated with continuous oral lenalidomide (20 mg/day). The primary end point was to evaluate efficacy according to the rate of disease control at 4 months. Secondary objectives were progression-free survival (PFS) and safety. RESULTS: Most of the 45 patients enrolled and treated had serous histology (78%) and a single line of prior chemotherapy (73%). Median platinum-free interval (PFI) was 11.3 months (range 6.9-56.8). Clinical benefit at 4 months was 38% [95% confidence interval (CI) 23% to 53%]. A 59% disease control rate was reported in patients with a PFI >12 months versus 24% with PFI of 6-12 months (P = 0.023). Four patients had RECIST partial responses and 21 had stable disease. CA125 responses were reported in eight patients, including one complete response. Median PFS was 3.4 months (95% CI 2.4-4.4). Most frequent toxicity was hematologic, notably grade 3-4 neutropenia in 29% of patients, along with fatigue (69%), gastrointestinal toxicity (constipation 53%, abdominal pain 49%, diarrhea 38%, nausea/vomiting 36%) and thrombosis (11%). Eight patients withdrew due to related toxicity. CONCLUSIONS: Lenalidomide shows interesting efficacy in late recurrent ovarian cancer patients. Toxicity was mainly hematologic, gastrointestinal and venous thrombosis. Future studies will evaluate combination of lenalidomide with chemotherapy agents. CLINICALTRIALSGOV: NCT01111903.

[Alteration in quality of life in anorexia nervosa and improvement under treatment: validation of a new questionnaire, the QUAVIAM]. / Altération de la qualité de vie dans l'anorexie mentale et amélioration sous traitement : validation d'un nouveau questionnaire, le QUAVIAM.

Anorexia nervosa (AN) is a chronic and often severe eating disorder, which could have a serious impact on various life domains. AN may lead to physical, mental, behavioural and socioprofessional impairment. Thus, one could expect a poor quality of life (QoL) in AN patients. QoL is certainly a key factor to provide quantitative measurement of treatment efficacy that will facilitate clinical decision-making and treatment planning. Despite that QoL was rarely prospectively analyzed in AN patients, one could conclude that AN patients showed reduced QoL, as compared to normal controls and other psychiatric-disordered patients. It seems that mental health components of QoL are more impaired than the physical ones in AN patients, who showed a modest impact in the physical domain. Thus, our aim was to analyse the QoL using a new, French, questionnaire, the QUAVIAM (qualité de vie dans l'anorexie mentale). After a bibliography research (including EDE, EDI, SF-36, QOL.ED), the choice of 12 themes, regrouped in six scores, was made by three eating disorder specialists and two recovered patients. For each score, 10 to 15 questions were written by the experts, and then corrections and validation were made by the five experts and 21 patients. After this, we prospectively determined the reproducibility (3 days interval), the specificity, and the sensitivity for short-term change in patients exhibiting an "active" AN (n=54, mean age: 31 ± 9 yrs, mean BMI: 14.1 ± 2.8 kg/m(2), AN duration: 2.6 ± 1.9 yrs), and again after cognitive behavioral therapy (CBT). We also analyzed the QUAVIAM score and subscores in 48 recovering patients and in 56 subjects without eating disorder. The QUAVIAM final version (61 questions) was collected in 76 patients and the 56 healthy controls matched for sex and age. Its reproducibility was 91% (intra-questionnaire) and 94% (inter-questionnaire), its specificity 98% (versus controls; P<0.0001) and its sensitivity 99%. The QUAVIAM global score of the AN patients was more impaired (389 ± 87) than that of the recovering patients (157 ± 82) and the normal controls (89 ± 49; P<0.0001). Each of the six subscores was higher (more altered) in active AN than in recovering AN patients and in normal subjects: the somatic, the psychological, the hedonic, the socioprofessional, the affective and the TCA-related ones (P<0.001 for each comparison). The QUAVIAM global score and its subscores were significantly improved (decreased) by the 3-month CBT: 385 ± 25 before and 189 ± 30 after CBT (P<0.0001). The changes were observed for all the subscales (P<0.0001). The somatic subscore did not decrease less than the other subscores. Thus, the present study permits proposing the QUAVIAM for analysis of physical, mental, behavioural and socioprofessional impairment or improvements in AN patients.

[Triggers of bulimia and compulsion attacks: validation of the "Start" questionnaire]. / Les inducteurs des crises dans la boulimie et la compulsion : validation du questionnaire « Start ¼

AIM: There are few published studies on the triggers of binge eating in anorexia nervosa of binge/purging subtype (BPAN), bulimia nervosa (BN) and binge eating disorder (BED). PATIENTS AND METHODS: We validated in 29 patients (10 BPAN, 10 BN and 9 BED) the perspicuity, the clarity and the intra- (doubles) and inter- (test-retest) reproducibility of a 24-item Start questionnaire on the triggers of binge eating. Then the Start questionnaire was administered to 176 patients (65 BPAN, 62 BN and 59 BED patients) being 27.5+9.1 yr old, having 15+9 binge eating (BE) episodes/week, with a mean binge duration of 1 hr 36min (+ 38min)/day. RESULTS: BE episodes occurred mainly during the second part of the day: afternoon after work (67% of the patients), "tea" time (55%), evening after dinner (42%) and at night (22%). The principal place for BE episodes was at home (96%). The BED patients avoided binges at the parents' home (89%) more often than the BPAN (62%, P<0.02). The binges occurred mainly in the living room (44%), in the kitchen (43%), and less in the bedroom (31%). Hunger pangs seemed to be a trigger of binges in 31% of the patients, and a stronger trigger in BED (42%) than in the BPAN and BN patients (24%; P=0.04). Binge eating episodes could occur despite a high satiety level (just after lunch or dinner) in 29% of the BN and in 16% of the BED patients (P<0.02). Concerning food, the major triggers were high energy-density food (77%) and comfort food (60%), such as chocolate, cakes, bread and pasta. The food consumed for binge episodes (in-binge food) was more often a strong trigger than the other food (not used for binges): olfaction (19% versus 10%), sight (52% versus 25%) and placing in the mouth (71% versus 26%; P<0.02 for all, in the 3 groups). Being tired could be a strong trigger in 37% of the patients, but "being aroused" in the other 38 % of the patients. Stressful events (65%), anxiety (74%), "being under pressure" or irritated (51% and 55%) were of course major triggers in a majority of the patients, as well as sadness (61%), feeling of powerlessness (62%), inefficiency (73%) and depressive state (71%). Flashback from traumatism (sexual trauma in 17% of the patients) was a strong trigger of binges more often in BPAN and BED (44%) than in BN (23%; P<0.05). The binge eating was painful (and "not at all a pleasure") in 69% of the patients, but could also be a relaxing behavior in 31% of the patients, more often in the BED (43%) than in the BPAN patients (20%; P<0.05). The binge eating behavior was quoted as obsessive in 63% of BPAN, 92% of BN and only 34% of BED patients (P<0.001). The patients said that they were unable to avoid the binge (76% of the patients), more often in BPAN and BN than in BED patients (P<0.01). As a whole, 62% of BPAN, 89% of BN and only 4 % of BED patients (P<0.05) were unable to avoid purging (vomiting). In 12% of the cases, there was a pleasure felt when binging. For the other patients, shame, filth and incapacity were the feelings related to binges in 58% of the BPAN, 45% of BN and 43% of BED patients (P<0.04). The global score of addiction (zero=not addicted, 10=very addicted) was 8.56+1.2 in BPAN, 8.42+1.5 in BN and 6.74+1.1 in BED patients (NS between BPAN and BN; P<0.01 between BPAN and BN on the one hand and BED on the other). CONCLUSION: The present study has demonstrated the usefulness of the Start questionnaire. It also evidences the key role of intrinsic factors, both metabolic and emotional, as strong triggers for binge eating episodes in BPAN, BN and BED. It has also demonstrated the role of environmental determinants.

A prognostic nomogram to predict overall survival in patients with platinum-sensitive recurrent ovarian cancer.

BACKGROUND: Patients with platinum-sensitive recurrent ovarian cancer have variable prognosis and survival. We extend previous work on prediction of progression-free survival by developing a nomogram to predict overall survival (OS) in these patients treated with platinum-based chemotherapy. PATIENTS AND METHODS: The nomogram was developed using data from the CAELYX in Platinum-Sensitive Ovarian Patients (CALYPSO) trial. Multivariate proportional hazards models were generated based on pre-treatment characteristics to develop a nomogram that classifies patient prognosis based on OS outcome. We also developed two simpler models with fewer variables and conducted model validations in independent datasets from AGO-OVAR Study 2.5 and ICON 4. We compare the performance of the nomogram with the simpler models by examining the differences in the C-statistics and net reclassification index (NRI). RESULTS: The nomogram included six significant predictors: interval from last platinum chemotherapy, performance status, size of the largest tumour, CA-125, haemoglobin and the number of organ sites of metastasis (C-statistic 0.67; 95% confidence interval 0.65-0.69). Among the CALPYSO patients, the median OS for good, intermediate and poor prognosis groups was 56.2, 31.0 and 20.8 months, respectively. When CA-125 was not included in the model, the C-statistics were 0.65 (CALYPSO) and 0.64 (AGO-OVAR 2.5). A simpler model (interval from last platinum chemotherapy, performance status and CA-125) produced a significant decrease of the C-statistic (0.63) and NRI (26.4%, P < 0.0001). CONCLUSIONS: This nomogram with six pre-treatment characteristics improves OS prediction in patients with platinum-sensitive ovarian cancer and is superior to models with fewer prognostic factors or platinum chemotherapy free interval alone. With independent validation, this nomogram could potentially be useful for improved stratification of patients in clinical trials and also for counselling patients.

Prognostic factors for patients treated for a recurrent FIGO stage III ovarian cancer: a retrospective study of 108 cases.

AIMS: To determine overall survival of patients treated for a first relapse of FIGO stage III ovarian cancer, outside of randomized trial, with a long term follow-up and to identify prognostic factors. MATERIALS AND METHODS: A consecutive series of 108 patients treated for a first relapse of a FIGO stage III ovarian cancer was retrospectively included from December 1999 to November 2004. Each patient was treated with platinum-based chemotherapy in case of late (>6 months) relapse and with salvage chemotherapy without platinum in case of <6 months relapse. For statistical analysis the studied parameters were age, histological subtype, the completeness of initial surgery, disease-free period, localization of the relapse, clinical response to second-line chemotherapy, the completeness of secondary cytoreductive surgery (SCS) when it was performed. RESULTS: Median follow-up from the first relapse was 40 months. From the 108 patients, 35 underwent SCS. Median overall survival from the first relapse was 13 months in case of no SCS or non-optimal SCS and 35 months for patient with an optimal SCS (p = 0.006). In a multivariate analysis age, disease-free period, the clinical presentation of the relapse, completeness of SCS and response to second line chemotherapy appeared to be independent prognostic factors. CONCLUSIONS: Prognostic factors of ovarian cancer relapse are directly or indirectly linked with the feasibility of a complete SCS. Thus in the case of an ovarian cancer relapse, the feasibility of SCS must be considered in order to give the patient the best chance to experience its complete removal.

Outcome in AN adult patients: a 13-year follow-up in 484 patients.

BACKGROUND: To study the long-term prognosis of anorexia nervosa (AN), 484 adult AN patients were followed on a mean duration of 13 years. RESULTS: The mortality rate was 1.2%. Eight factors were linked to the lack of recovery at 2 years: low BMI at discharge, low energy and fat intakes, high drive for excessive exercising, high score for perfectionism, for interpersonal distrust and for anxiety, use of tube-feeding and adhesion to treatment (P<0.02). Four factors explained the risk of the binge/purging form at 2 years: having had binge-eating disorder and overweight before AN, having had purging episodes within the first 2 years of AN; having had very high energy intakes through meals and being not treated by tube-feeding. During the 13-year follow-up, very few binge/purging patients turned out to have the restrictive form. Two main factors explained 67% of the variance of menses recovery: having a BMI>18.5 kg/m(2); and having no physical hyperactivity. The recovery rate increased with the elapsing of relapse-free time (P=0.02). After a 13.5-year follow-up, 292 out of the 484 patients were recovered (60.3%), 25.8% had a relatively good outcome, 6.4% a bad outcome and 6.4% a severe outcome. Very few factors were identified as predictors of a good outcome (binge-eating/purging subtype, personality disorder).

[Intraperitoneal chemotherapy in the treatment of advanced ovarian cancer]. / La chimiothérapie intrapéritonéale dans les cancers avancés de l'ovaire.

The standard treatment for advanced ovarian cancer consist in complete surgical debulking and intravenous platin and taxane based chemotherapy. Despite research efforts, a lot of patients still die from peritoneal carcinomatosis. The aim of our work was to present the state of art about intraperitoneal chemotherapy. Intraperitoneal chemotherapy (IPC): three multi-institutional randomised trials showed that platin based IPC gave better results in term of overall and disease free survival when compared to standard intravenous treatment. Even so, IPC is not yet becoming a new international standard of treatment because a high rate of morbidity. Hyperthermic Intraperitoneal chemotherapy (HIPEC) represents an innovative alternative to IPC. HIPEC is based on a complete surgical debulking without any visible mass and an intraperitoneal chemotherapy with synergy of hyperthermia. Phase II trails have shown its feasibility. Randomised trials are needed to assess its efficiency in improving survival.

Subliminal fear priming potentiates negative facial reactions to food pictures in women with anorexia nervosa.

BACKGROUND: To investigate hedonic reactivity and the influence of unconscious emotional processes on the low sensitivity to positive reinforcement of food in anorexia nervosa (AN). METHOD: AN and healthy women were exposed to palatable food pictures just after a subliminal exposure to facial expressions (happy, disgust, fear and neutral faces), either while fasting or after a standardized meal (hunger versus satiety). Both implicit [facial electromyographic (EMG) activity from zygomatic and corrugator muscles, skin conductance, heart rate, and videotaped facial behavior] and explicit (self-reported pleasure and desire) measures of affective processes were recorded. RESULTS: In contrast to healthy women, the AN patients did not display objective and subjective indices of pleasure to food pictures when they were in the hunger states. Pleasure to food cues (liking) was more affected than the desire to eat (wanting) in AN patients. Subliminal 'fear faces' increased corrugator muscle reactivity to food stimuli in fasting AN patients, as compared to controls. CONCLUSIONS: The results suggest that unconscious fear cues increase the negative appraisal of alimentary stimuli in AN patients and thus contribute to decreased energy intake.

Lapatinib in metastatic breast cancer.

Lapatinib is an oral, small-molecule, dual kinase inhibitor that targets both HER2 and the EGF receptor. Lapatinib was approved in June 2008 in Europe for the treatment of advanced HER2-positive breast cancer. Promising results in trastuzumab-refractory metastatic breast cancer were obtained from Phase I, II and III studies in combination with chemotherapy. Diarrhea and rash are the most common side-effects and are mostly moderate and treatable. Cardiac toxicity occurs rarely and mostly as an asymptomatic and reversible decrease of left ventricular ejection fraction. Unlike trastuzumab, some data show that lapatinib could cross the blood-brain barrier, with some evidence of activity in treating or preventing brain metastases. Its evaluation is actively ongoing, in combination with trastuzumab and in the adjuvant setting.

Variety enhances food intake in humans: role of sensory-specific satiety.

Twenty-one subjects were studied to evaluate the effect of renewal of sensory stimulations of previously eaten foods on sensory-specific satiety and intake. The subjects ate French fries then brownie cakes ad libitum in three situations: "monotonous" - fries then brownies were consumed alone; "simultaneous" - condiments (ketchup and mayonnaise for the fries, vanilla cream and whipped cream for the brownies) were added during intakes; "successive" - after intake of fries alone, ketchup then mayonnaise were available with fries and, after intake of brownies alone, vanilla cream then whipped cream were offered with brownies. The quantities eaten in the "simultaneous" and "successive" situations were higher (p<0.001) than those in the "monotonous" one (1485+/-582 and 1682+/-777 kcal vs 1195+/-552 kcal, respectively). In the "successive" situation, hedonic ratings for fries diminished during intake but increased after the introduction of ketchup, leading to additional intake of fries. Similarly, hedonic ratings for brownies diminished during intake and increased after the introduction of vanilla cream leading to additional brownie intake (mayonnaise and whipped cream had no significant effect). Food variety, obtained by adding condiments can increase food intake in the short term. The mechanism by which food consumption is increased after the addition of condiments is introduced is at least partly related to the attenuation of sensory-satiety for a given food.

Safety and pharmacokinetics of paclitaxel and the oral mTOR inhibitor everolimus in advanced solid tumours.

Everolimus displays antiproliferative effects on cancer cells, yields antiangiogenic activity in established tumours, and shows synergistic activity with paclitaxel in preclinical models. This study assessed the safety and the pharmacokinetic interactions of everolimus and paclitaxel in patients with advanced malignancies. Everolimus was dose escalated from 15 to 30 mg and administered with paclitaxel 80 mg m(-2) on days 1, 8, and 15 every 28 days. Safety was assessed weekly, and dose-limiting toxicity (DLT) was evaluated in cycle 1. A total of 16 patients (median age 54.5 years, range 33-69) were entered; 11 had prior taxane therapy for breast (n=5), ovarian (n=3), and vaginal cancer (n=1) or angiosarcoma (n=2). Grade 3 neutropenia in six patients met the criteria for DLT in two patients receiving everolimus 30 mg weekly. Other drug-related grade 3 toxicities were leucopenia, anaemia, thrombocytopenia, stomatitis, asthenia, and increased liver enzymes. Tumour stabilisation reported in 11 patients exceeded 6 months in 2 patients with breast cancer. Everolimus showed an acceptable safety profile at the dose of 30 mg when combined with weekly paclitaxel 80 mg m(-2), warranting further clinical investigation.

Hypercholesterolaemia in anorexia nervosa: frequency and changes during refeeding.

UNLABELLED: High total cholesterol (TC) is common in patients with anorexia nervosa (AN), but its mechanisms remain unclear. PATIENTS AND METHODS: We prospectively studied plasma lipoprotein (LP), haptoglobin, free (f) T3, fT4, TSH, transthyretin and albumin in 120 malnourished adult AN patients (BMI: 13.5+/-1.5 kg/m(2)), 116 non-AN malnourished patients and 119 healthy subjects, matched for age and gender. RESULTS: In 18% of our AN patients, TC was higher than 270 mg/100mL (in non-AN: 5%; P<0.01). TC, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and HDL2 levels were higher in AN patients than in non-AN patients (P<0.001). Low TC (<150 mg/100mL) and LP levels were observed in 8% of AN patients, but only when BMI was less than 13 kg/m(2). Cholesterol ester transfer protein (CETP) activity was higher in AN patients than in healthy subjects. LP was positively correlated with BMI, albumin, fT3 and haptoglobin levels. In AN patients, there was a biphasic LP profile (low values when BMI was very low, normal values in an intermediate state, and high values when BMI was highest and where bulimia was also present). CONCLUSION: In AN, both high and low cholesterol-rich LP levels were observed. Low T3 and low catabolism allow LP to be maintained, while CETP activity increases cholesterol turnover as an adaptation to its low intake. In severely malnourished AN patients, this fails and LP drops. On the other hand, LP values were higher in the bingeing-purging type of AN than in the restrictive type. Recovery from AN results in the normalization of the LP profile.