Abstract
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.
Original language | English (US) |
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Pages (from-to) | 505-511 |
Number of pages | 7 |
Journal | Annals of Oncology |
Volume | 25 |
Issue number | 2 |
DOIs | |
State | Published - Feb 2014 |
Keywords
- Cisplatin
- Etoposide
- Everolimus
- Phase I
- Small-cell lung cancer
ASJC Scopus subject areas
- Hematology
- Oncology