Publication Date:
2008-11-16
Description:
Maintenance therapy with the monoclonal anti-CD20 antibody Rituximab (R) improves clinical outcome in patients with follicular lymphoma in complete or partial remission (CR, PR) after induction therapy. However, optimal dosing schedule and duration of maintenance therapy are still under investigation. Commonly applied regimen include four doses of 375mg/m2 Rituximab once a week every 6 months, one dose every 3 months, or one dose every 2 months. Maintenance is usually given for 2 years. In addition to clinical trials, pharmacokinetic (PK) studies could help determining optimal dosing of Rituximab. PK values have been obtained during induction therapy in several trials and an association between drug trough levels and clinical effectiveness has been established (25μg/ml in responding patients). However, data on Rituximab PK during maintenance therapy are lacking. The Austrian Cooperative Study Group for Cancer Drug Therapy (AGMT) has conducted a phase II trial in 33 patients with follicular lymphoma in CS III/IV with an induction therapy with 6 cycles of Rituximab (375mg/m2 i.v., day 1), Fludarabine (30mg/m2 p.o., day 2–4)) and Mitoxantron (10mg/m2 i.v., day 1) every 4 weeks (R-FM) (NHL9). Thirty two patients obtaining a CR, CRu or PR received maintenance treatment with Rituximab 375mg/m2 every 2 months for 1 year. Pharmacokinetic data for Rituximab were obtained during induction and maintenance treatment in 16 of these patients. All patients converted from BCL2/IgH PCR positivity to negativity in peripheral blood after R-FM induction. PK serum concentrations during induction corresponded well to known data: A steady increase in pre- and post-dose levels was observed with increasing cycle number. Median, minimum and maximum Rituximab serum concentrations are given in the upper panel of Table 1: Table 1. Serum concentrations (μg/ml) during R-FM induction and two-monthly maintenance treatment with 375mg/m2 of Rituximab. R-FM Induction Cycle 1 2 4 6 (Q 4 weeks) min. med. max. min. med. max. min. med. max. min. med. max. Pre-dose N.A.
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
Permalink