Weekly carboplatin plus neoadjuvant anthracycline-taxane-based regimen in early triple-negative breast cancer: a prospective phase II trial by the Breast Cancer Task Force of the Belgian Society of Medical Oncology (BSMO).

AIM: To evaluate the pCR rate and toxicity of the addition of weekly carboplatin (Cp) to paclitaxel (wP) and dose-dense (dd) epirubicin/cyclophosphamide (EC) in an open-label phase II study in TNBC patients. METHODS: Patients were included if they had stage II and III TNBC and received wP (80 mg/m2/week) concurrent with weekly Cp (AUC = 2) for 12 weeks, followed by bi-weekly epirubicin (90 mg/m2) and cyclophosphamide (600 mg/m2) plus granulocyte colony-stimulating factor (G-CSF) for four cycles, followed by surgery. The primary endpoint was the rate of pCR [(ypT0/isypN0)]. Secondary endpoints included safety and drug delivery. RESULTS: Sixty-three eligible patients were included. Median age was 51 years (range 29-74); 88.9% had stage II disease, 46% were clinically node positive, and 77.8% had grade 3 tumors. Fifty-four percent achieved a pCR. Twelve percent missed two or more doses of wP, whereas at least two cycles of EC were missed in 9.5%. The rate of tolerance without delays or dose reductions is very low (16%). Sixty-two percent had G3/4 neutropenia. Febrile neutropenia occurred in 18 patients of which more than eighty percent occurred during EC despite primary prophylaxis with G-CSF. Thrombocytopenia grade 3/4 was noticed in 11 pts. Three patients developed grade 3 peripheral neuropathy. CONCLUSION: The addition of weekly carboplatin to neoadjuvant paclitaxel and dd EC leads to a pCR rate comparable to prior studies (54%). However, hematological toxicity and febrile neutropenia rate was unexpectedly high. Future investigations could focus on reversing the sequence, which may lead to better hematological tolerability

Efficacy and Safety of Lanreotide Autogel in the Treatment of Clinical Symptoms Associated With Inoperable Malignant Intestinal Obstruction: A Prospective Phase II Study.

Inoperable malignant intestinal obstruction (IMIO) is a severe complication in patients with cancer, usually gastrointestinal or gynecologic in origin. For patients with IMIO, there is a need to relieve symptoms and limit nasogastric tube (NGT) use. Previous studies have suggested the efficacy of somatostatin analogues in relieving obstruction-related symptoms, such as nausea, vomiting, and pain. The purpose of this study was to assess the efficacy of lanreotide autogel 120 mg (LAN 120 mg) in the management of symptoms resulting from IMIO in patients with advanced cancer. This single-arm, multicenter study enrolled 52 patients mostly with advanced gastrointestinal or ovarian malignant tumors (35 patients with NGT and 17 patients without NGT). Patients received 1 deep subcutaneous injection of LAN 120 mg. Evaluations were performed on days 7, 14, and 28. The primary end point was the percentage of responding patients before or at day 7. Response was defined as ≤2 vomiting episodes per day (for patients without NGT at baseline) or no vomiting recurrence (after NGT removal) during at least 3 consecutive days at any time point between treatment and day 7. Responders at day 28 were offered a second LAN 120 mg injection and followed up until day 56. The proportion of responders in the intention-to-treat population was 24 of 52 (46.2%), which was significantly greater than the reference proportion of 30% (P = 0.0055). Patients without NGT had a higher response (88.2%) than patients with NGT (25.7%) and had a steady trend for clinical improvement that led to sustainable responses. Median time to response was 9 days for the overall population, 3 days for patients without NGT, and 14 days for patients with NGT (P < 0.0001). Our study is the first to use long-acting LAN 120 mg in patients with IMIO and suggests an effect in controlling clinical symptoms in patients with and without NGT at baseline. The safety profile of LAN 120 mg was similar to that reported in other indications. ClinicalTrials.gov identifier: NCT02275338

Hématologie, soins palliatifs et sciences humaines : une rencontre réflexive qui déplace les représentations

La mise en place d’un séminaire d’éthique clinique, « Hématologie et soins palliatifs » a invité autour de la table acteurs de sciences humaines et sociales et cliniciens à réfléchir à l’articulation entre hématologie et soins palliatifs. Méthodologie : seize participants issus des sciences humaines et sociales et de la médecine palliative et hématologique se sont rencontrés dans une démarche d’éthique clinique, autour de cas cliniques vécus et considérés comme complexes d’un point de vue clinique et éthique. Résultats : la réflexion initiale se basait sur des questions organisationnelles entre médecine palliative et hématologie. Elle s’est déplacée au cours du séminaire, invitant à un questionnement d’ordre identitaire sur deux types de médecine, dites curative ou palliative. L’attention à la subjectivité des cliniciens et l’apport des sciences humaines et sociales dans la réflexion ont proposé un nouveau paradigme de soin, basé sur l’attention au mouvement de vie du sujet malade. Discussion : la méthodologie de l’éthique clinique a permis d’élaborer des pistes de transformation des pratiques professionnelles

Hématologie, soins palliatifs et sciences humaines : une rencontre réflexive qui déplace les représentations

INTRODUCTION : la mise en place d’un séminaire d’éthique clinique, « Hématologie et soins palliatifs » a invité autour de la table acteurs de sciences humaines et sociales et cliniciens à réfléchir à l’articulation entre hématologie et soins palliatifs. Méthodologie : seize participants issus des sciences humaines et sociales et de la médecine palliative et hématologique se sont rencontrés dans une démarche d’éthique clinique, autour de cas cliniques vécus et considérés comme complexes d’un point de vue clinique et éthique. RÉSULTATS : la réflexion initiale se basait sur des questions organisationnelles entre médecine palliative et hématologie. Elle s’est déplacée au cours du séminaire, invitant à un questionnement d’ordre identitaire sur deux types de médecine, dites curative ou palliative. L’attention a la subjectivité des cliniciens et l’apport des sciences humaines et sociales dans la réflexion ont proposé un nouveau paradigme de soin, basé sur l’attention au mouvement de vie du sujet malade. DISCUSSION : la méthodologie de l’éthique clinique a permis d’élaborer des pistes de transformation des pratiques professionnelles [Titre en angalais : Hematology, palliative care, and human sciences: a dialogue that changes portrayals

Prospective randomized study comparing docetaxel, estramustine, and prednisone with docetaxel and prednisone in metastatic hormone-refractory prostate cancer

PURPOSE: To assess the efficacy and toxicity of the addition of estramustine to docetaxel (D) for the treatment of metastatic hormone-refractory prostate cancer. PATIENTS AND METHODS: One hundred fifty patients were randomly assigned to D alone (35 mg/m(2) on days 2 and 9, every 3 weeks) or D in combination with estramustine (D/E; 280 mg orally three times a day on days 1 to 5 and 8 to 12, every 3 weeks). All patients received prednisone (10 mg/d). The primary end point was prostate-specific antigen (PSA) response rate, which was defined as a decrease in PSA >/= 50% from baseline. The study was powered to test the hypothesis that D/E would improve the PSA response rate by 25%. RESULTS: The PSA response rate was not statistically different between the two groups. PSA of less than 4 ng/mL occurred in 29 (41%) of 71 patients receiving D/E and in 17 (25%) of 69 patients receiving D (P = .05). No significant differences were found for median time to PSA progression (D/E, 6.9 months; D, 7.3 months) or median overall survival time (D/E, 19.3 months; D, 21 months). More patients had at least one grade 3 or 4 toxicity with D/E (45%) compared with D (21%; P = .005), mainly as a result of grade 3 or 4 GI toxicity (P = .05). Serious adverse events were more frequent with D/E (n = 20) than with D (n = 9; P = .04). CONCLUSION: The addition of estramustine to weekly D does not provide any clinically relevant advantage. Both regimens are well tolerated, although the toxicity profile favors D without estramustine

Abiraterone acetate plus prednisone for the Management of Metastatic Castration-Resistant Prostate Cancer (mCRPC) without prior use of chemotherapy : report from a large, international, real-world retrospective cohort study

Background: With the recent introduction of novel treatment options, real-world data from patients with metastatic castration-resistant prostate cancer (mCRPC) are required to better understand the impact on routine clinical practice. This study primarily aimed to describe the time to treatment failure (TTF) of mCRPC patients treated with abiraterone acetate plus prednisone or the corticosteroid of choice (AAP) in the pre-chemotherapy setting. Other relevant outcomes, clinical and treatment characteristics of these patients were also evaluated. Methods: This retrospective, observational study collected data from chemotherapy-naïve mCRPC patients treated with AAP from four European countries. Kaplan-Meier curves were used to estimate TTF, progression-free survival (PFS), and time to first skeletal-related event. The impact of baseline characteristics on TTF and PFS was explored using univariate and multivariate Cox proportional hazard models. Log-rank test was used to assess the potential role of duration of response to ADT in predicting response to AAP treatment. Results: Data from 481 eligible patients (Belgium: 68; France: 61; Germany: 150; UK: 202) were analysed. At AAP initiation, the median age of patients was 75.0 years (interquartile range [IQR]: 69.0–81.0), and the median PSA was 56.2 ng/mL (IQR: 22.2–133.1), with over 50% of patients presenting an ECOG score of 0 or 1. Visceral metastases were present in 7.5% of patients; an exclusion criterion in the COU-AA-302 clinical trial. The median TTF with AAP was 10.0 months (95%CI: 9.2–11.1) and the median PFS was 10.8 months (95%CI: 9.6–11.8). Shorter TTF was significantly associated with higher ALP (> 119 units/L), higher PSA (> 56.2 ng/mL), or poorer ECOG PS scores at AAP initiation (p < 0.05). Patients with longer duration of response to ADT (≥12 months) presented longer TTF and longer time to progression (p < 0.0001). Conclusions: This European real-world study provides valuable insights into the characteristics, treatment, and outcomes of chemotherapy-naïve patients with mCRPC who received AAP in routine clinical practice. Treatment effectiveness of AAP in the real-world is maintained despite patients having poorer clinical features at initiation than those observed in the COU-AA-302 trial population

La collection Ad usum Delphini. Volume II

Suite du premier volume consacré à la collection Ad usum Delphini dans son ensemble, à son élaboration et à ses aspects bibliophiliques et pédagogiques, ce second volet aborde l’analyse de chacun des volumes publiés concernant les auteurs anciens. Les différents collaborateurs se sont attachés à la fois à éclaircir la personnalité et la carrière de ces savants du XVIIe siècle, parfois jeunes ou peu connus lors de leur participation à l’équipe dauphine, à examiner leur travail philologique, mais aussi à le replacer dans son contexte historique et dans l’histoire de l’édition des classiques. Il ne s’agit pas de dire ici si ces éditions sont « bonnes » au regard de notre temps, mais à examiner leur facture, les motifs de leurs réussites comme de leurs silences, ce qu’elles ont apporté à l’histoire du texte autant que ce qu’elles ont figé dans sa transmission. L’ensemble des deux ouvrages forme la première étude exhaustive scientifique sur le fond de la collection Ad usum Delphini