Phase II trial of individualized rituximab dosing for patients with CD20-positive lymphoproliferative disorders.
OBJECTIVE
To determine the feasibility and efficacy of pharmacokinetic (PK) -based maintenance dosing of rituximab and possibly design a more rational maintenance schedule.


METHODS
Patients with CD20-positive lymphoproliferative disorders were treated with four weekly infusions of rituximab 375 mg/m(2). All patients without progressive disease were then monitored for 1 year and received a single infusion of 375 mg/m(2) when the level decreased below 25 microg/mL.


RESULTS
Twenty-nine of 31 patients were assessable with a variety of histologic subtypes. The overall response rate (ORR) for the entire group was 59% with 27% complete responses (CRs) and 32% partial responses. The median PFS for all patients was 19 months, with a median follow-up of 25 months. In 22 patients with low-grade non-Hodgkin's lymphoma (LGNHL), the ORR was 63% with 36% CR and median progression-free survival (PFS) has not been reached. Of 29 assessable patients, 22 were available for PK-based maintenance. The median time to repeat bolus was 5 months (range, 1 to 9 months) for the first, 3.5 months (range, 2 to 5 months) for the second, and 3 months (range, 2 to 4 months) for the third infusion. Ninety-five percent of patients required three or fewer infusions to be maintained in the therapeutic range.


CONCLUSIONS
Individualized PK dosing for rituximab produced efficacy comparable to other published maintenance strategies. PK data from this trial suggest that a rational maintenance strategy in patients with LGNHL would be a single dose of 375 mg/m(2) of rituximab every 3 to 4 months.
Gordan
Lucio N
LN
Division of Hematology/Oncology, Department of Medicine, University of Florida College of Medicine, Gainesville, FL 32610, USA.
Grow
William B
WB
Pusateri
Annette
A
Douglas
Vonda
V
Mendenhall
Nancy P
NP
Lynch
James W
JW
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20 / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D016393:Lymphoma, B-Cell / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D019233:Retreatment; D000069283:Rituximab; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D000970:Antineoplastic Agents; D000069283:Rituximab