Evaluation de la chimiothérapie associant carboplatine, cisplatine et vinorelbine dans le traitement des cancers bronchiques non a petites cellules (efficacité et toxicité)

L'incidence du cancer bronchique non à petites cellules est en constante progression dans le monde. Le nombre de nouveaux cas diagnostiqués dans les centres hospitaliers généraux était de 5000 et représente environ 25% des nouveaux cas en France. La plupart de ces cancers ( 40%) sont diagnostiqués à un stade métastatique. Nous nous sommes intéressé à la prise en charge de ces patients dans un centre hospitalier général et avons réalisé une étude rétrospective d'une cohorte de patients ayant bénéficié d'un protocole de chimiothérapie par P.C.V. :cisplatine (25 mg/mø à J2 et J3), carboplatine (200 mg/mø à J1) et vinorelbine (30 mg/mø à J8) tous les 21 jours, ce protocole ayant démontré une efficacité intéressante en phase II avec une faible toxicité chez des patients présentant un cancer non à petites cellules de stade IIIA, IIIB et IV. De 1996 à 2003, 46 patients ont été traité selon ce protocole : 74% d'hommes, âge moyen 62,2 ans, avec un indice de performance conservé ( inférieur à 3). Nos résultats montrent une médiane de survie globale de 36 semaines, une survie sans progression de 19 semaines et un taux de survie à un an de 34%. La toxicité hématologique a été très importante avec 46% de neutropénie, 26% d'aplasie fébrile, 36% d'anémie et 17% de thrombopénie. Devant les résultats de la toxicité de ce protocole, il ne paraît pas légitime de continuer cette chimiothérapie et le P.C.V est abandonnéAMIENS-BU Santé (800212102) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

A phase II study of cisplatin with intravenous and oral vinorelbine as induction chemotherapy followed by concomitant chemoradiotherapy with oral vinorelbine and cisplatin for locally advanced non-small cell lung cancer

BACKGROUND: Concomitant platinum-based chemotherapy and radiotherapy (CT-RT) is the recommended treatment for unresectable locally advanced stage III non-small cell lung cancer (NSCLC). We conducted a phase II study to evaluate the efficacy and safety of fractionated oral vinorelbine with cisplatin as induction CT followed by CT-RT. METHODS: Patients with stage III NSCLC received 2 induction cycles of intravenous vinorelbine 25 mg/m(2) and cisplatin 80 mg/m(2) on day 1 and oral vinorelbine 60 mg/m(2) on day 8. Responding patients received 2 more cycles of cisplatin 80 mg/m(2) on day 1 and oral vinorelbine 20 mg on days 1, 3 and 5 concomitantly with radiotherapy 2 Gy daily, 5 days/week for a total of 66 Gy. RESULTS: Seventy patients, median age 61 years, were enrolled. Overall response rate (ORR) was 50.0%; Disease Control Rate was 81.42%. Median PFS was 14.58 months [95% CI, 10.97-18.75]. Median OS was 17.08 months [95% CI, 13.57-29.57]. One-year and 2-year survival rates were 68.6% [95% CI, 57.7-79.4] and 37%. One patient had a grade 3 pulmonary radiation injury and 26.5% had graded 1/2 esophagitis. CONCLUSION: In non-operable IIIA-IIIB NSCLC, the combination oral vinorelbine (fractionated fixed dose) plus cisplatin, during concomitant CT-RT, could offer a well-tolerated option, with comparable activity to I.V. vinorelbine-based chemoradiotherapy regimens. TRIAL REGISTRATION: ClinicalTrials.gov, NCT0183903

Neurological complications induced by immune checkpoint inhibitors: a comprehensive descriptive case-series unravelling high risk of long-term sequelae

International audienceNeurological immune-related adverse events are complications of programmed-cell death 1 or programmed-cell death 1 ligand immunotherapies that can be life threatening and often lead to anticancer immunotherapy withdrawal. Scant clinical data are available that integrate the clinical presentation, therapeutic management and long-term outcome. All consecutive adult patients treated by programmed-cell death 1 or programmed-cell death 1 ligand immunotherapies, given alone or in combination with other treatment, who experienced a neurological immune-related adverse event with a severity grade ≥2 in Paris Saclay-University hospitals were investigated from June 2014 to February 2019. The frequency of neurological immune-related adverse events was calculated from the prospective Registre des Effets Indésirables Sévères des Anticorps Monoclonaux Immunomodulateurs en Cancérologie cohort. Forty patients presenting with 51 distinct neurological immune-related adverse events were included. The prevalence of grade ≥2 neurological immune-related adverse events was estimated to be 1.22% in the Registre des Effets Indésirables Sévères des Anticorps Monoclonaux Immunomodulateurs en Cancérologie cohort. Among 40 patients with neurological immune-related adverse events, 65% received programmed-cell death 1 or programmed-cell death 1 ligand monotherapy and 35% received a combination of programmed-cell death 1 plus anti-CTLA4 (Common Terminology Criteria for Adverse Events). Clinical neurological presentations were peripheral (48%), central (35%), or mixed (18%). The severity of neurological immune-related adverse events was grade 2 for 14 (35%) and ≥grade 3 for 26 patients (65%). The mortality rate related to neurological immune-related adverse events was 8%. Corticosteroid treatment led to neurological recovery in 74%. Long-term follow-up highlighted that 53% of patients experienced long-term neurological sequelae. Five patients were rechallenged by programmed-cell death 1 monotherapy without recurrence of their neurological immune-related adverse event(s). Neurological immune-related adverse events induced by programmed-cell death 1 or programmed-cell death 1 ligand are rare but are severe with a mortality rate of 8% and long-term sequelae for 53% of patients. Corticosteroids should be started when neurological immunological complications are identified to avoid long-term sequelae