Etoposide pharmacokinetics impact the outcomes of lymphoma patients treated with BEAM regimen and ASCT: a multicenter study of the LYmphoma Study Association (LYSA)

{Relationships between pharmacokinetic (PK) parameters of etoposide and toxicity survivals were reported in cancer patients treated at standard doses. The clinical impact of PK variations of etoposide high doses has never been explored in lymphoma patients. The primary objective of LYMPK study was to prospectively assess the impact of etoposide PK parameters on outcomes in lymphoma patients receiving high-dose chemotherapy regimen (carmustine, cytarabine, etoposide and melphalan) followed by autologous stem cell transplant (ASCT). Individual etoposide PK parameters were estimated with a previously reported bi-compartment model using NONMEMA (R) program. The impact of PK parameters on toxicity and survival was assessed using univariate/multivariate analyses. A total of 91 patients with malignant lymphoma [non-Hodgkin's lymphoma (NHL): 79; Hodgkin's lymphoma: 12] at first line (n = 49) or relapse (n = 42) were enrolled in five centers. Large inter-individual variabilities in individual PK values were found for the same administration doses. In NHL patients, cumulative higher trough concentrations over the eight administrations of the first cycle (TotC (min), categorized by the median 58.71 mg/L) had significant prognostic value regarding the 5-year progression-free survival (PFS: 73.6 vs 46.5 %