Abstract A95: The determination of the maximum tolerated dose (MTD) of MGCD265 on an intermittent schedule: Phase I study results (Study 265-102).
Notice bibliographique
Résumé
Abstract Background: MGCD265 is an orally administered multi-targeted receptor tyrosine kinase (RTK) inhibitor that specifically targets Met RTK and the vascular endothelial growth factor (VEGF) receptors (VEGFR1, VEGFR2 and VEGFR3). Additional RTK targets include Tie-2 and Ron. These kinases are known to be involved in tumor development and angiogenesis. Methods: This was a Phase I dose-escalation study in patients with advanced solid tumors (classic 3+3 design). Oral MGCD265 was administered intermittently (one week on/one week off) over 28-day cycles. The primary objectives were to determine the MTD, dose limiting toxicities (DLTs) and safety of MGCD265. Secondary objectives were pharmacokinetics (PK) profile, pharmacodynamic (PD) change, and anti-tumor activity of MGCD265. Results: Forty seven patients with advanced solid tumors were recruited (median age: 60 years old, M/F: 23/24, ECOG 0/1/2: 10/33/4). MGCD265 was administered once a day (QD) in the initial cohorts and then twice daily (BID) in the last two cohorts. The observed DLTs were grade 3 mood alteration and grade 3 fatigue in one patient and grade 3 hemoptysis in another patient at the dose of 170 mg/m2 BID (n=6). Therefore, the previously tested dose level of 128 mg/m2 BID was determined to be the MTD. The most frequent treatment-related adverse events included diarrhea, nausea, and fatigue. Most of these AEs were reported as grade 1 or 2 in severity. Fourteen patients experienced serious AEs; none were considered related to study medication. MGCD265 has a terminal half-life of approximately 23 hours. Exposure on the QD schedule appeared to increase with increasing doses from 24 mg/m2 up to 96 mg/m2 and approached a plateau with subsequent dose increases up to 340 mg/m2. With the BID schedule, higher exposures at steady state were achieved and a plateau was less evident with the two doses tested (128 and 170 mg/m2 BID). Four patients (papillary renal cell, sarcomatoid bladder, neuroendocrine, and head & neck cancers) had prolonged stable disease (range: ∼6–14 cycles). The patient with sarcomatoid bladder cancer was stable for 10 cycles and exhibited decreases in Met and phospho-Met protein expression, as well as a change in intact vascular structures, in a post-treatment biopsy sample. Conclusions: MGCD265 is safe and well tolerated when using the intermittent schedule of administration. Based on the results obtained in other trials with daily administration, MGCD265 will be administered continuously in future studies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr A95.
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 ».