The Saskatchewan Experience for Using FCR in Treatment of CLL – A Comparison of Oral Versus IV Regimens

Abstract 4613

The addition of Rituximab to the combination of Fludarabine and Cyclophosphamide (FCR) for treatment of patients with chronic lymphocytic leukemia (CLL) was recently found by two phase III studies, REACH and CLL8, to be superior to the combination of Fludarabine and Cyclophosphamide alone (Robak T, et al. J Clin Oncol. 2010; 28(10): 1756 – 1765; Hallek M, et al. Lancet 2010; 376(9747): 1164 – 1174). As a result, treatment with FCR was approved for use in Saskatchewan beginning in January of 2010. The characteristic regimen for FCR involves administration of rituximab 375 mg/m² intravenously (IV) on day 1 followed by fludarabine 25 mg/m² and cyclophosphamide 250 mg/m² (FC) administered IV on days 1–3 for a total of 6 treatment cycles at intervals of 28 days. Due to the large geographic area of the province of Saskatchewan, patients are often required to travel extensive distances for appointments and treatment. This has resulted in an adaptation of the FCR regimen to incorporate the administration of oral fludarabine (40 mg/m²) and cyclophosphamide (300 mg/m²) for 3 days following the IV rituximab. In many cases, this has allowed patients to receive Rituximab IV on one day and then to continue the remaining days of treatment with oral therapy from home.

This study retrospectively reviewed all patients in Saskatchewan who received FCR treatment for CLL since January 2010. 32 charts were reviewed and examined for the overall efficacy, regimen toxicity and tolerability to the 2 different regimens. Of the 32 patients, 16 patients received an IV regimen and 16 received a regimen that involved receiving FC orally. Of those who received the IV regimen, 2 were female and 14 were male. The average age was 58 (38 – 77). Of those who received the oral regimen, 5 were female and 11 were male. The average age was 62 (48 – 75). Eleven of the 32 patients received FCR as a first line therapy (IV: 6; Oral: 5).The remaining 21 patients received FCR as either a second, third or fourth line therapy (IV: 10, Oral: 11).

Results of this study showed that 75% of those who received IV treatment completed 6 cycles, while only 50% of patients who were on an oral regimen were able to complete 6 cycles (OR = 3.00). Infectious complications encountered during treatment were the most common cause for dose reductions for the IV regimen (43.3%) while neutropenia and/or thrombocytopenia accounted for 36.7%. The most common reason for a dose reduction in the oral regimen was neutropenia and/or thrombocytopenia (61.5%). The average number of dose delays for patients receiving both the IV and oral regimen was similar at 1 (0 – 4). Neutropenia and/or thrombocytopenia were the most common reasons for dose delays in both the IV and oral regimens (75% IV, 65% Oral). The oral regimen resulted in hospitalization of 43.8% of patients, while only 12.5% of patients who received the IV regimen required hospitalization at some point during treatment (OR = 5.44). Reasons for hospitalization for those patients on the oral regimen included febrile neutropenia (5), infection (3) and observation (1). The complete remission (CR) and partial remission (PR) rates for the 2 regimens were similar (IV regimen: CR = 56.3%, PR = 25%; Oral regimen: CR = 56.3%, PR = 25%).

In conclusion, this retrospective study has shown that an oral regimen of FCR resulted in similar response rates to the IV FCR regimen. However, the oral regimen does result in more hospitalizations and an inability to complete treatment. Whether using an oral FCR regimen remains feasible for treating regions that cover a large geographic territory requires further study.