Marketing authorization procedures for advanced cancer drugs: exploring the views of patients, oncologists, healthcare decision makers and citizens in France

International audienceBackground. The past decades have seen advances in cancer treatments in terms of toxicity and side effects but progress in the treatment of advanced cancer has been modest. New drugs have emerged improving progression free survival but with little impact on overall survival, raising questions about the criteria on which to base decisions to grant marketing authorizations and about the authorization procedure itself. For decisions to be fair, transparent and accountable, it is necessary to consider the views of those with relevant expertise and experience. Methods. We conducted a Q-study to explore the views of a range of stakeholders in France, involving: 54 patients (18 months after diagnosis); 50 members of the general population; 27 oncologists; 19 healthcare decision makers; and 2 individuals from the pharmaceutical industry. Results. Three viewpoints emerged, focussing on different dimensions entitled: 1) ‘Quality of life (QoL), opportunity cost and participative democracy’; 2)‘QoL and patient-centeredness’; and 3) ‘Length of life’. Respondents from all groups were associated with each viewpoint, except for healthcare decision makers, who were only associated with the first one. Conclusion. Our results highlight plurality in the views of stakeholders, emphasize the need for transparency in decision making processes, and illustrate the importance of a re-evaluation of treatments for all 3 viewpoints. In the context of advanced cancer, our results suggest that QoL should be more prominent amongst authorization criteria, as it is a concern for 2 of the 3 viewpoints

Perception de l'information à travers une brochure sur la recherche biomédicale en cancérologie.

International audienceL’objectif de cette étude a été d’évaluer l’opinion des patients sur le contenu d’une brochure d’information concernant les objectifs de la recherche biomédicale en oncologie et sur le respect de leurs droits en cas de participation à un essai clinique. Cent vingt-neuf patients traités pour cancer à l’institut Paoli-Calmettes (Marseille) et éligibles pour un essai clinique ont été inclus dans l’étude. La brochure d’information leur a été remise avec la lettre d’information et le formulaire de consentement éclairé relatifs à l’essai. Après lecture, les patients ont rempli un questionnaire d’enquête (10 items). Près de 84 % d’entre eux ont jugé que la brochure était compréhensible par la majorité des patients. Cependant, 18,2 % réclamaient plus d’information sur les différentes phases des essais cliniques et 39,4 % plus d’information sur leurs propres traitements. Par ailleurs, 41,4 % n’étaient pas ou pas entièrement assurés de recevoir toute l’information en cas de participation à un essai clinique et environ 23 % que leurs droits seraient respectés. Seulement 9,6 % des patients connaissaient l’existence du Comité consultatif de protection des personnes se prêtant à la recherche biomédicale (CCPPRB) ; son intervention (information fournie dans la brochure) n’était pas considérée comme rassurante par 28,6 % des patients. Cette étude a d’importantes implications pour les patients éligibles pour des essais cliniques

A spin-crossover iron( ii ) coordination polymer with the 8-aminoquinoline ligand: synthesis, crystal structure and magnetic properties of [Fe(aqin) 2 (4,4′-bpy)](ClO 4 ) 2 ·2EtOH (aqin = 8-aminoquinoline, 4,4′-bpy = 4,4′-bipyridyl)

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Efficacy and tolerance of a scalp-cooling system for prevention of hair loss and the experience of breast cancer patients treated by adjuvant chemotherapy

International audienceThe applicability and efficacy of a scalp cooling system were studied in 105 breast cancer patients receiving four cycles of adjuvant chemotherapy with mitoxantrone + cyclophosphamide (NC chemotherapy). Women accepting the scalp-cooling system were compared for alopecia both against those who refused and against a "reference" group of 109 patients similarly treated but without being offered a scalp-cooling system. Hair loss in the 105 study patients was evaluated by nurses using World Health Organization (WHO) criteria at each cycle of chemotherapy. Concomitantly, tolerance and side-effects of the helmet were also recorded in 48 accepting patients. Similarly to reference group patients, a subsample of 27 accepting patients self-assessed hair loss using a specific questionnaire measuring its frequency and severity and the distress associated with this symptom. Nurses' ratings ( n = 105) indicated that hair loss frequency was constantly lower, at each cycle of chemotherapy, in study patients with scalp-cooling system ( n = 77) than in those without ( n = 28). Differences between the two groups were statistically significant at cycles 1 and 3 ( P < 0.05). When compared with those reported by reference group patients ( n = 109), study patients' self-measures of alopecia frequency ( n = 27) provided even more marked results than those achieved by nurses (cycles 1-3: P < 0.01; cycle 4: P < 0.05). Tolerance was generally good and no scalp metastasis was observed among the 77 accepting patients followed up. This study demonstrates that scalp cooling was an effective method of protection against hair loss caused by NC chemotherapy. Its routine use as part of adjuvant chemotherapy, especially in cancers with low prevalences of scalp metastasis, should be seriously considered

Que signifie pour les participants la notion de « résultats » d’un essai thérapeutique ?

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Quality of life of breast cancer patients receiving high-dose-intensity chemotherapy: impact of length of cycles

International audiencehis study was designed to measure treatment side-effects and quality of life (QL) of 47 nonmetastatic breast cancer patients subjected to a dose-intensity increase while receiving a sequential high dose chemotherapy (doxorubicin+cyclophosphamide - 4 cycles). The dose-intensity increase was obtained by shortening the length of cycles from 21 to 14 days. Treatment side-effects were self-assessed in terms of frequency and associated distress in cycles 1 and 3 by using a specific side-effect self-report questionnaire (19 items). Multidimensional QL measurement was performed at inclusion and before the start of cycles 2 and 4, by using the EORTC QLQ-C30. Pain was evaluated by patients on a visual analogue scale at the same times as QL evaluation. Patients' self-ratings indicated that the total number of symptoms, the number of symptoms rated by patients as quite or very distressing, and symptom frequency were comparable whatever the length of cycle. Overall, although underestimating most patients' symptoms, physicians' reports provided similar results. However, analysis of multidimensional QL showed that, in comparison to standard administration of 4 cycles of 21 days, there was a more significant deterioration of the QLQ-C30 global QL score ( P=0.01) at the second cycle of chemotherapy and of the physical functioning score ( P=0.02) at the fourth cycle when the cycle length was reduced. This study, although limited by a small patient cohort, has shown that shortening cycles to increase dose intensity had relatively few consequences on adverse treatment effects but a highly negative impact on patients' quality of life

Stem Cells Inhibition by Bevacizumab in Combination with Neoadjuvant Chemotherapy for Breast Cancer

International audiencePreclinical works have suggested cytotoxic chemotherapies may increase the number of cancer stem cells (CSC) whereas angiogenesis inhibition may decrease CSC proliferation. We developed a proof of concept clinical trial to explore bevacizumab activity on breast CSC. Breast cancer patients requiring preoperative chemotherapy were included in this open-label, randomized, prospective, multicenter phase II trial. All received FEC-docetaxel combination, and patients randomized in the experimental arm received concomitant bevacizumab. The primary endpoint was to describe ALDH1 (Aldehyde dehydrogenase 1) positive tumor cells rate before treatment and after the fourth cycle. Secondary objectives included safety, pathological complete response (pCR) rate, disease-free survival (DFS), relapse-free survival (RFS), and overall survival (OS). Seventy-five patients were included. ALDH1+ cells rate increase was below the predefined 5% threshold in both arms for the 32 patients with two time points available. Grade 3 or 4 adverse events rates were similar in both arms. A non-significant increase in pCR was observed in the bevacizumab arm (42.6% vs. 18.2%, p = 0.06), but survival was not improved (OS: p = 0.89; DFS: p = 0.45; and RFS: p = 0.68). The increase of ALDH1+ tumor cells rate after bevacizumab-based chemotherapy was less than 5%. However, as similar results were observed with chemotherapy alone, bevacizumab impact on breast CSC cells cannot be confirmed

A multicentre randomised controlled trial to evaluate the efficacy, morbidity and functional outcome of endoscopic transanal proctectomy versus laparoscopic proctectomy for low-lying rectal cancer (ETAP-GRECCAR 11 TRIAL): rationale and design

Abstract Background Total mesorectal excision is the standard surgical treatment for mid- and low-rectal cancer. Laparoscopy represents a clear leap forward in the management of rectal cancer patients, offering significant improvements in post-operative measures such as pain, first bowel movement, and hospital length of stay. However, there are still some limits to its applications, especially in difficult cases. Such cases may entail either conversion to an open procedure or positive resection margins. Transanal endoscopic proctectomy (ETAP) was recently described and could address the difficulties of approaching the lower third of the rectum. Early series and case-control studies have shown favourable short-term results, such as a low conversion rate, reduced hospital length of stay and oncological outcomes comparable to laparoscopic surgery. The aim of the proposed study is to compare the rate of positive resection margins (R1 resection) with ETAP versus laparoscopic proctectomy (LAP), with patients randomly assigned to each arm. Methods/design The proposed study is a multicentre randomised trial using two parallel groups to compare ETAP and LAP. Patients with T3 lower-third rectal adenocarcinomas for whom conservative surgery with manual coloanal anastomosis is planned will be recruited. Randomisation will be performed immediately prior to surgery after ensuring that the patient meets the inclusion criteria and completing the baseline functional and quality of life tests. The study is designed as a non-inferiority trial with a main criterion of R0/R1 resection. Secondary endpoints will include the conversion rate, the minimal invasiveness of the abdominal approach, postoperative morbidity, the length of hospital stay, mesorectal macroscopic assessment, functional urologic and sexual results, faecal continence, global quality of life, stoma-free survival, and disease-free survival at 3 years. The inclusion period will be 3 years, and every patient will be followed for 3 years. The number of patients needed is 226. Discussion There is a strong need for optimal evaluation of the ETAP because of substancial changes in the operative technique. Assessment of oncological safety and septic risk, as well as digestive and urological functional results, is particularily mandatory. Moreover, benefits of the ETAP technique could be demonstrated  in post-operative outcome. Trial registration ClinicalTrial.gov: NCT02584985 . Date and version identifier: Version n°2 – 2015 July 6

Simple Aspiration versus Drainage for Complete Pneumothorax: A Randomized Noninferiority Trial

International audienceRationale: Management of first episodes of primary spontaneous pneumothorax remains the subject of debate.Objectives: To determine whether first-line simple aspiration is noninferior to first-line chest tube drainage for lung expansion in patients with complete primary spontaneous pneumothorax.Methods: We conducted a prospective, open-label, randomized noninferiority trial. Adults aged 18–50 years with complete primary spontaneous pneumothorax (total separation of the lung from the chest wall), recruited at 31 French hospitals from 2009 to 2015, received simple aspiration (n = 200) or chest tube drainage (n = 202) as first-line treatment. The primary outcome was pulmonary expansion 24 hours after the procedure. Secondary outcomes were tolerance of treatment, occurrence of adverse events, and recurrence of pneumothorax within 1 year. Substantial discordance in the numerical inputs used for trial planning and the actual trial rates of the primary outcome resulted in a reevaluation of the trial analysis plan.Measurement and Main Results: Treatment failure occurred in 29% in the aspiration group and 18% in the chest tube drainage group (difference in failure rate, 0.113; 95% confidence interval [CI], 0.026–0.200). The aspiration group experienced less pain overall (mean difference, −1.4; 95% CI, −1.89, −0.91), less pain limiting breathing (frequency difference, −0.18; 95% CI, −0.27, −0.09), and less kinking of the device (frequency difference, −0.05; 95% CI, −0.09, −0.01). Recurrence of pneumothorax was 20% in this group versus 27% in the drainage group (frequency difference, −0.07; 95% CI, −0.16, +0.02).Conclusions: First-line management of complete primary spontaneous pneumothorax with simple aspiration had a higher failure rate than chest tube drainage but was better tolerated with fewer adverse events