A phase ib dose-escalation study of everolimus combined with cisplatin and etoposide as first-line therapy in patients with extensive-stage small-cell lung cancer

B. Besse, R. S. Heist, V. A. Papadmitrakopoulou, D. R. Camidge, J. T. Beck, P. Schmid, C. Mulatero, N. Miller, S. Dimitrijevic, S. Urva, I. Pylvaenaeinen, K. Petrovic, B. E. Johnson

    Résultats de recherche: Contribution à un journalArticleRevue par des pairs

    22 Citations (Scopus)

    Résumé

    Background: This phase Ib study aimed to establish the feasible everolimus dose given with standard-dose etoposide plus cisplatin (EP) for extensive-stage small-cell lung cancer (SCLC). Patients and methods: An adaptive Bayesian dose-escalation model and investigator opinion were used to identify feasible daily or weekly everolimus doses given with EP in adults with treatment-naive extensive-stage SCLC. A protocol amendment mandated prophylactic granulocyte colony-stimulating factor (G-CSF). Primary end point was cycle 1 dose-limiting toxicity (DLT) rate. Secondary end points included safety, relative EP dose intensity, pharmacokinetics, and tumor response. Results: Patients received everolimus 2.5 or 5 mg/day without G-CSF (n = 10; cohort A), 20 or 30 mg/week without G-CSF (n = 18; cohort B), or 2.5 or 5 mg/day with G-CSF (n = 12; cohort C); all received EP. Cycle 1 DLT rates were 50.0%, 22.2%, and 16.7% in cohorts A, B, and C, respectively. Cycle 1 DLTs were neutropenia (cohorts A and B), febrile neutropenia (all cohorts), and thrombocytopenia (cohorts A and C). The most common grade 3/4 adverse events were hematologic. Best overall response was partial response (40.0%, 61.1%, and 58.3%in cohorts A, B, and C, respectively). Conclusions: Everolimus 2.5 mg/day plus G-CSF was the only feasible dose given with standard-dose EP in untreated extensive-stage SCLC.

    langue originaleAnglais
    Pages (de - à)505-511
    Nombre de pages7
    journalAnnals of Oncology
    Volume25
    Numéro de publication2
    Les DOIs
    étatPublié - 1 janv. 2014

    Contient cette citation