Chemoimmunotherapy with low-dose fludarabine and cyclophosphamide and high dose rituximab in previously untreated patients with chronic lymphocytic leukemia.
OBJECTIVE
Chemoimmunotherapy combining fludarabine, cyclophosphamide, and rituximab (FCR) is an active regimen for untreated patients with chronic lymphocytic leukemia (CLL) with 70% complete responses (CRs) and 95% overall responses (ORs). However, grade 3/4 neutropenia was reported in 52% of cycles of treatment. The purpose of this trial was to maintain the high responses but reduce the toxicity of FCR by decreasing the fludarabine and cyclophosphamide (FCR-Lite).


METHODS
We conducted a single arm study of FCR-Lite which includes maintenance rituximab in 50 untreated CLL patients. Patients were evaluated for response using both the 1996 National Cancer Institute Working Group (NCIWG) guidelines and the 2008 guidelines. Two thirds of patients were treated by community physicians.


RESULTS
The median age was 58 years (range, 36 to 85 years); 20 patients had Rai stage 1, 22 had Rai stage 2, and eight had Rai stage 3 and 4. The OR and CR rates were 100% and 79%, respectively, using the 1996 NCIWG guidelines and 100% and 77% using the 2008 guidelines. Median duration of complete response was 22.3 months (range, 5.2 to 42.5 months) and none of the complete responders have relapsed. Grade 3/4 neutropenia was noted in 13% of the cycles of therapy.


CONCLUSIONS
FCR-Lite is highly effective in previously untreated CLL patients. Grade 3/4 neutropenia was dramatically reduced compared to standard FCR and our data demonstrated FCR-Lite can be safely administered in the community setting.
Foon
Kenneth A
KA
Department of Medicine and Biostatistics, University of Pittsburgh School of Medicine, Graduate School of Public Health, University of Pittsburgh Cancer Institute, University of Pittsburgh Medical Center Cancer Centers, PA, USA. kfoon@nvcancer.org
Boyiadzis
Michael
M
Land
Stephanie R
SR
Marks
Stanley
S
Raptis
Anastasios
A
Pietragallo
Louis
L
Meisner
Dennis
D
Laman
Andrew
A
Sulecki
Mathew
M
Butchko
Allyson
A
Schaefer
Patricia
P
Lenzer
Diana
D
Tarhini
Ahmad
A
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000493:pharmacokinetics; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents / Q000008:administration & dosage; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D000069283:Rituximab; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D000069283:Rituximab; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine