In this report, we present our results of the biochemotherapy combination of
rituximab (Rituxan), a monoclonal antibody against CD20, with fludarabine (Fludara) and cyclophosphamide
(Cytoxan, Neosar). During course 1, rituximab is given at a slow rate at 375
mg/m² on day 1 followed by fludarabine at 25 mg/m² and cyclophosphamide at 250
mg/m² on days 2-4. During subsequent courses (2-6), rituximab is given at
500 mg/m² on day 1 and fludarabine and cyclophosphamide are given at the same
doses but on days 1-3. From November 1999 to July 2001, 167 patients were
registered, and 102 patients are currently evaluable after more than 6 months of
Patient characteristics are as follows: median age, 59 years (range: 36-81
years); males, 72.5%; Rai stage IV, 42%; median platelet count, 117 × 109
cells/L (range: 15-367 × 109 cells/L); median hemoglobin, 12.1 g/dL (range:
6.8-16.5 g/dL); median white blood cell count, 52 × 109 cells/L (range: 1.3-584
× 109 cells/L); three or more lymph node sites involved, 59%;
beta-2-microglobulin greater than 3 mg/dL, 83%; performance status of ≤ 1, 79%.
The median number of prior treatments was 2: 14.7% of the patients had received
alkylating agents only, 58.8% had been sensitive to fludarabine-containing
regimens, and 26.4% had been resistant to fludarabine.
The median follow-up time is 13+ months. Using National Cancer Institute
criteria, the complete response (CR) rate is 23%; nodular partial response, 14%;
partial response, 36%; and no response, 20.9%. The total response rate was
72.2%. Of 13 patients (38%) in CR, five had immunoglobulin rearrangements
undetectable by polymerase chain reaction. Responses based on prior therapy are
summarized as follows:
Frequent toxicities related to rituximab included chills and fever. Other
toxicities included nausea/vomiting, hypotension, and dyspnea. Serious
toxicities from the treatment included eight episodes of pneumonia, seven
episodes of neutropenic fever, five of sepsis, and one prolonged
myelosuppression. A total of 26 patients have died.
CONCLUSION: The combination of fludarabine, cyclophosphamide, and rituximab
is a very active program for patients with previously treated CLL.