Pharmacokinetically-targeted dosed everolimus maintenance therapy in lymphoma patients.

Autor: Schoch LK; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, 401 N. Broadway room 1363, Baltimore, MD, 21287, USA., Asiama A; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, 401 N. Broadway room 1363, Baltimore, MD, 21287, USA., Zahurak M; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, 401 N. Broadway room 1363, Baltimore, MD, 21287, USA., Shanbhag S; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, 401 N. Broadway room 1363, Baltimore, MD, 21287, USA., Hurtt J; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, 401 N. Broadway room 1363, Baltimore, MD, 21287, USA., Sawyer K; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, 401 N. Broadway room 1363, Baltimore, MD, 21287, USA., Swinnen LJ; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, 401 N. Broadway room 1363, Baltimore, MD, 21287, USA., Wagner-Johnston N; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, 401 N. Broadway room 1363, Baltimore, MD, 21287, USA., Jones RJ; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, 401 N. Broadway room 1363, Baltimore, MD, 21287, USA., Ambinder RF; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, 401 N. Broadway room 1363, Baltimore, MD, 21287, USA., Gladstone DE; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, 401 N. Broadway room 1363, Baltimore, MD, 21287, USA. dgladst1@jhmi.edu.
Jazyk: angličtina
Zdroj: Cancer chemotherapy and pharmacology [Cancer Chemother Pharmacol] 2018 Feb; Vol. 81 (2), pp. 347-354. Date of Electronic Publication: 2017 Dec 13.
DOI: 10.1007/s00280-017-3499-y
Abstrakt: Background: Everolimus, an mTOR inhibitor, is active in refractory lymphomas. However, toxicity with flat dosing limits its usage. Speculatively, pharmacokinetically-targeted dosing could improve tolerability. Therefore, we studied serum-trough dosing with rituximab as maintenance after high-dose cyclophosphamide (HDC) consolidation in lymphoma patients.
Patients/methods: After HDC, everolimus was dosed to serum trough levels (goal 3-15 ng/mL), with quarterly rituximab infusions for 1 year while maintaining < grade II non-hematologic and < grade III hematologic toxicities. Adult patients in first PR/CR with: mantle cell, transformed, double-hit, or high risk chronic lymphocytic leukemia or in second PR for any relapsed B cell lymphoma were eligible. Prophylaxis was given for encapsulated organisms, HSV and PCP. Serum IgG levels were maintained > 500 mg/dL.
Results: 49 patients, median age: 59.0 years enrolled; MCL (26), CLL (10), transformed lymphoma (7), and other histologies (6). During the life of the study, the most frequent everolimus dosing has been 2.5 mg daily or 2.5 mg every other day; at these doses, serum levels are within the therapeutic range and non-hematologic toxicity is rare. At a median follow-up of 27.1 months, three patients remain on active therapy. Two patients withdrew secondary to potentially-attributable adverse events including a bacterial pneumonia and a viral pneumonia; this low rate of discontinuation compares well to other long-term everolimus trials. While a 58 and 76% EFS at 30 months for the entire cohort and MCL cohort, respectively, compares similarly to previously published HDC/rituximab data, longer follow-up is required.
Conclusions: Pharmacokinetically-targeted dosing appears to increase everolimus tolerability. This finding may be applicable to other patient populations.
Databáze: MEDLINE
Externí odkaz: