Abstract B81: Phase I/II trial of vorinostat in combination with etoposide in pediatric patients with relapsed/refractory solid tumors.
Notice bibliographique
Résumé
Abstract Introduction: Vorinostat has been shown to potentiate DNA damage induced by topoisomerase II inhibitors in a sequence dependent fashion. A multi-center, open label phase I study with escalating doses of vorinostat in combination with etoposide was conducted to establish the safety of the combination in pediatric patients with refractory solid tumors to determine the maximum tolerated dose (MTD), dose limiting toxicity (DLT) and recommended phase II dose (RP2D) of this regimen. Methods: Eligible patients were ≤21 years of age with relapsed/refractory solid tumors including central nervous system tumors. Study design consisted of a standard 3+3 dose escalation schema. Vorinostat was administered once daily for days 1-4 of the treatment cycle in escalating doses (125 mg/m2, 160 mg/m2, 210 mg/m2, and 270 mg/m2). Etoposide was administered at a fixed dose of 100 mg/m2/day on days 3-5 of the treatment cycle. Etoposide was administered 4 hours after administration of vorinostat. Each treatment cycle was 21 days. Intrapatient dose escalation was not permitted. The maximum tolerated dose (MTD) was defined as the highest dose level with an observed incidence of dose-limiting toxicity (DLT) in no more than one of six patients within the first treatment cycle. Histone acetylation, histone phosphorylation, and gene expression profiling were performed as correlative studies. Exploratory studies included assessment of symptom distress by self report in children between the ages of 10 and 18 with the MSAS (10-18) instrument. Results: Twenty-one patients (CNS 12, neuroblastoma 6, Wilms’ tumor 1, rhabdomyosarcoma 1, hepatoblastoma 1) were enrolled on study and 19 patients were treated. Median age was 12 years (range 4-20 years); 11 males and 10 females with a median performance status 90% were included. One patient experienced a DLT (Gr 4 platelet count decreased) at the 1stdose level (125 mg/m2 vorinostat,100 mg/m2 etoposide). The predominant Grade 3 and 4 toxicities attributed to the combination included white blood cell count decreased (45%), neutrophil count decreased (55%), lymphocyte count decreased (30%), and platelet count decreased (25%). Grade 3-4 events in ≤10% of patients included anemia (10%), hypophosphatemia (5%), and infection (5%). Stable disease was reported in 4 patients (CNS 3, sarcoma 1). Biologic correlative studies and symptom distress data will be presented. Conclusion: Vorinostat followed in combination with etoposide was found to be safe and well tolerated in children with refractory solid tumors. The recommended phase II dose was established at vorinostat 270 mg/m2 and etoposide 100 mg/m2 and will be evaluated in an ongoing phase II study in pediatric patients with sarcoma. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):B81. Citation Format: Tanya M. Trippett, Amy Smith, Kathleen Neville, Susan Chi, Aru Narendran, Robert Arceci, Jennifer Direnzo, Lia Gore. Phase I/II trial of vorinostat in combination with etoposide in pediatric patients with relapsed/refractory solid tumors. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr B81.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».