Abstract 2242: A randomized phase 2 study of the cyclin-dependent kinase (CDK) inhibitor Dinaciclib (SCH 727965) in patients with non-small cell lung cancer (NSCLC)
Notice bibliographique
Résumé
Abstract Dinaciclib is a potent, selective inhibitor of CDKs 1, 2, 5, and 9 with preclinical activity against NSCLC cell lines and tumor xenografts. NSCLC tumors have numerous defects in cell cycle regulation (abnormal p16/cyclin D/Rb pathway, cyclin E overexpression, loss of p27/KIP1). The rationale for this study is that abnormal cell cycle regulation may predispose NSCLC cells to the pro-apoptotic effects of dinaciclib. A randomized, multicenter, open-label phase 2 study was conducted to compare the efficacy of dinaciclib and erlotinib (150 mg PO QD) in patients (pts) with locally advanced previously treated Non-Small Cell Lung Cancer (NSCLC). Dinaciclib 50 mg/m2 was administered by 2-hour i.v. infusion once every 21 days. Key inclusion criteria included ≤ 2 prior chemotherapy regimens and measurable disease. Patients were randomized to treatment with dinaciclib or erlotinib using an adaptive Bayesian design to adjust the randomization ratio in favor of the more active arm. Patients could cross-over to dinaciclib after progressing on erlotinib. This design provides a comparison of dinaciclib versus erlotinib and assesses dinaciclib activity in patients who've progressed on erlotinib. Primary endpoints: Time-to-progression (TTP) for pts receiving upfront treatment; and response rate (RR) for pts who crossed over to dinaciclib. Sixty-four pts received upfront treatment with either erlotinib (n=49) or dinaciclib (n=15). Seventeen patients crossed over from upfront erlotinib arm to dinaciclib. Median age was 65 (range 46-82) with a median of 1 (range 1-2) prior chemotherapy regimens and median ECOG performance status of 1 (0-2). The median number of treatment cycles was 2 (range 1-19), with 27/32 treated pts receiving > 1 cycle of treatment with dinaciclib. Tumor responses were assessed using RECIST. No dinaciclib responses were observed in either upfront or cross over arms. Two of forty-nine (4%) evaluable subjects receiving upfront erlotinib were reported to have partial responses (PR). Analysis of TTP will be presented at the meeting. Treatment-related grade 1 and 2 toxicities, occurring in >30% of pts included diarrhea (76%), neutropenia (66%), vomiting (59%), nausea (55%), fatigue (38%) and leukopenia (38%). The most common treatment-related grade 3 and 4 toxicities, occurring in 2 or more pts were neutropenia (60%), leukopenia (32%), vomiting (20%), diarrhea (16%), fatigue (12%), nausea (12%), electrolyte imbalance (8%) and hyperuricemia (8%). PK results are pending and will be included in the final abstract. Dinaciclib has acceptable safety and tolerability in patients with NSCLC but did not demonstrate anti-tumor activity. In accordance with pre-specified rules of the adaptive design, patient enrollment was stopped initially in the crossover stage and in the upfront stage of the trial. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2242. doi:10.1158/1538-7445.AM2011-2242
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 | 0,001 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,001 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 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 ».