Randomized phase 2 study of the cyclin-dependent kinase inhibitor dinaciclib (MK-7965) versus erlotinib in patients with non-small cell lung cancer.
Lung Cancer
; 83(2): 219-23, 2014 Feb.
Article
en En
| MEDLINE
| ID: mdl-24388167
ABSTRACT
OBJECTIVES:
Dinaciclib (MK-7965, formerly SCH 727965), a novel, small-molecule inhibitor of cyclin-dependent kinases, has been shown to induce apoptosis in preclinical studies of human tumor cell lines, including non-small cell lung cancer (NSCLC) cells. Erlotinib, an epidermal growth factor receptor inhibitor, is approved for the treatment of advanced NSCLC as second- or third-line therapy. This phase 2, randomized, multicenter, open-label study compared dinaciclib with erlotinib in patients with previously treated NSCLC. MATERIALS ANDMETHODS:
The study was comprised of 2 parts in part 1, patients were randomized to either intravenous (IV) dinaciclib (50 mg/m2) or oral erlotinib (150 mg) using an adaptive Bayesian design that adjusted the randomization ratio in favor of the more active arm, and in part 2, patients who had progressed on erlotinib were permitted to cross over to receive dinaciclib at the same dosage as in part 1. Patients were followed until disease progression or death, initiation of nonstudy cancer treatment, discontinuation, or withdrawal of consent. The primary efficacy end point was time-to-progression (TTP) in part 1 and objective response rate (ORR) in part 2.RESULTS:
Based on Kaplan-Meier estimates, the median TTP was 1.49 months (95% confidence interval [CI] 1.31, 2.63) following initial treatment with dinaciclib, compared with 1.58 months (95% CI 1.38, 2.83) with erlotinib. No objective responses were observed following initial treatment with dinaciclib. Common severe (grade 3 or 4) drug-related adverse effects included neutropenia, leukopenia, vomiting, and diarrhea.CONCLUSIONS:
Dinaciclib, administered IV, was well tolerated at the 50 mg/m2 dose, but does not have activity as monotherapy in previously treated NSCLC. Evaluation of dinaciclib in combination with other agents for other indications including breast cancer and multiple myeloma is in progress.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Compuestos de Piridinio
/
Quinazolinas
/
Protocolos de Quimioterapia Combinada Antineoplásica
/
Carcinoma de Pulmón de Células no Pequeñas
/
Compuestos Bicíclicos Heterocíclicos con Puentes
/
Neoplasias Pulmonares
Tipo de estudio:
Clinical_trials
/
Etiology_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Adult
/
Aged
/
Aged80
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Lung Cancer
Asunto de la revista:
NEOPLASIAS
Año:
2014
Tipo del documento:
Article
País de afiliación:
Estados Unidos