HOUSTONAdding rituximab (Rituxan) to standard chemotherapy
increased complete remission (CR) rates for chronic lymphocytic leukemia (CLL)
and reduced the number of bone marrow cells expressing the CLL-associated
cell-surface markers CD5 and CD19, according to Michael J. Keating, MD.
"Fludarabine, cyclophosphamide, and rituximab (FCR) is the most active
regimen explored by our group in previously untreated CLL, and the toxicity
profile is similar to that seen with FC alone," said Dr. Keating,
professor of leukemia developmental research at the University of Texas M. D.
Anderson Cancer Center in Houston.
Rituximab was studied as part of the combination because
previous work had shown it to have significant dose-related efficacy in CLL and
to sensitize lymphoid cells to chemotherapy.
Dr. Keating reported data on
53 patients with previously untreated CLL, 41% of whom had Rai stage III or IV
disease. He pointed out that these patients were "somewhat younger than in
with a median age of 54 years (range 30-85).
60% Complete Responses
Patients were treated with fludarabine (25 mg/m2) and
cyclophosphamide (250 mg/m2) daily for 3 days for six courses every 4 weeks.
Rituximab was given at 375 mg/m2 on day 1 of course 1 and at 500
mg/m2 on day 1
of courses 2-6.
Dr. Keating reported a 92% overall response rate after 6
courses. This included 32 complete responses (60%), 9 (17%) nodular partial
remissions, and 8 (15%) non-nodular partial remissions. Levels of beta-2
microglobulin at baseline were the only significant predictors of response.
"After treatment with FCR, the median number of CD5/CD19
co-expressing cells in the bone marrow in responders was less than 1%,
significantly less than after treatment with FC without rituximab," Dr.
Keating said. Bone marrow in 12 of 17 (71%) CR patients studied had also become
PCR negative for immunoglobulin heavy chain rearrangement.
"Toxicities associated with the first infusion of
rituximab were mainly fever and chills or changes in blood pressure," Dr.
Keating said. "Toxicity grade was 1-2 in 61% and grade 3-4 in 14%. Adverse
reactions to rituximab in courses 2 through 6 were uncommon.
Toxicities associated with FC were nausea in 21% of courses,
associated with vomiting in 7%. Alopecia was noted in one patient. Neutropenia
was the most common hematologic toxicity and required dose reduction of FC in
21% of patients. No episodes of hemolytic anemia occurred. Chemical tumor lysis
was observed in three patients and clinical tumor lysis in two patients was
noted before allopurinol prophylaxis was initiated."