Faculty Collaboration Database

Phase I-II study of oxaliplatin, fludarabine, cytarabine, and rituximab combination therapy in patients with Richter's syndrome or fludarabine-refractory chronic lymphocytic leukemia. J Clin Oncol 2008 Jan 10;26(2):196-203

Date

01/10/2008

Pubmed ID

18182662

DOI

10.1200/JCO.2007.11.8513

Scopus ID

2-s2.0-38349163290 (requires institutional sign-in at Scopus site)   137 Citations

Abstract

PURPOSE: Richter's syndrome (RS) and fludarabine-refractory chronic lymphocytic leukemia (CLL) are associated with poor clinical outcomes. We conducted a phase I-II trial of oxaliplatin, fludarabine, cytarabine, and rituximab (OFAR) in these diseases.

PATIENTS AND METHODS: The OFAR regimen consisted of increasing doses of oxaliplatin (17.5, 20, or 25 mg/m(2)/d) on days 1 to 4 (phase I), fludarabine 30 mg/m(2) on days 2 to 3, cytarabine 1 g/m(2) on days 2 to 3, rituximab 375 mg/m(2) on day 3 of cycle 1 and day 1 of subsequent cycles, and pegfilgrastim 6 mg on day 6, every 4 weeks for a maximum of six courses. Dose-limiting toxicity (DLT) was defined as any nonhematologic, treatment-related toxicity >/= grade 3.

RESULTS: Fifty patients were treated (20 patients had RS, and 30 had CLL). The highest tolerated oxaliplatin dose was 25 mg/m(2), which was the highest dose tested. DLT was not observed. Pharmacodynamic analyses demonstrated enhanced leukemia cell killing by oxaliplatin in the presence of fludarabine and cytarabine. The overall response rates were 50% in RS and 33% in fludarabine-refractory CLL. The overall response rate in 14 patients with age >/= 70 years was 50%. Responses were achieved in seven (35%) of 20 patients with 17p deletion, two (29%) of seven patients with 11q deletion, all four patients with trisomy 12, and two (40%) of five patients with 13q deletion. The median response duration was 10 months. Toxicities were mainly hematologic; prolonged myelosuppression was not observed.

CONCLUSION: The OFAR regimen is highly active in RS and has activity in fludarabine-refractory patients with CLL. This regimen warrants further investigation in the treatment of these disorders.

Author List

Tsimberidou AM, Wierda WG, Plunkett W, Kurzrock R, O'Brien S, Wen S, Ferrajoli A, Ravandi-Kashani F, Garcia-Manero G, Estrov Z, Kipps TJ, Brown JR, Fiorentino A, Lerner S, Kantarjian HM, Keating MJ

Author

Razelle Kurzrock MD Center Associate Director, Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Aged
Antibodies, Monoclonal
Antibodies, Monoclonal, Murine-Derived
Antineoplastic Combined Chemotherapy Protocols
Chi-Square Distribution
Cytarabine
Drug Administration Schedule
Female
Humans
Infusions, Intravenous
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, Non-Hodgkin
Male
Middle Aged
Organoplatinum Compounds
Proportional Hazards Models
Research Design
Rituximab
Statistics, Nonparametric
Survival Analysis
Syndrome
Treatment Outcome
Vidarabine