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
2013; Elsevier BV; Volume: 25; Issue: 2 Linguagem: Inglês
10.1093/annonc/mdt535
ISSN1569-8041
AutoresBenjamin Besse, Rebecca S. Heist, V.A. Papadmitrakopoulou, D. Ross Camidge, J. Thaddeus Beck, Peter Schmid, C Mulatero, Neil Miller, Saša Dimitrijević, Shweta Urva, Ilona Pylvaenaeinen, Katarina Petrović, Bruce E. Johnson,
Tópico(s)Cancer therapeutics and mechanisms
ResumoBackgroundThis 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 methodsAn 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.ResultsPatients 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).ConclusionsEverolimus 2.5 mg/day plus G-CSF was the only feasible dose given with standard-dose EP in untreated extensive-stage SCLC.
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