Pentostatin, Cyclophosphamide, and Rituximab (PCR) Has Comparable Activity but Appears To Be Better Tolerated Than Fludarabine, Cyclophosphamide, and Rituximab (FCR) in Patients with Previously Treated Chronic Lymphocytic Leukemia.

Combination therapy with purine analogs, alkylators, and monoclonal antibodies has transformed the treatment paradigm in patients with CLL by dramatically enhancing both the quality and frequency of responses that can be achieved in these patients. However, combinations utilizing fludarabine as the purine analog have augmented myelosuppression and immunosuppression requiring careful attention to dosing and schedule in order to minimize these complications. Even with these precautions many patients are unable to complete the entire treatment program at full dose and for the planned number of cycles. Comparative experience with pentostatin indicates that it is less myelosuppressive than either fludarabine or cladribine. We previously reported our experience with pentostatin and cyclophosphamide. Subsequently, we have added rituximab to this active combination (PCR regimen) and treated a second cohort of 46 patients with previously treated CLL (32 patients) and other low grade lymphoid neoplasms (14 patients). The PCR regimen consists of pentostatin 4mg/m², cyclophosphamide 600mg/m², and rituximab 375mg/m² all given on a single day with anti-emetics, hydration, and careful monitoring of renal function. The treatment was administered every 3 weeks for a total of 6 treatments. Rituximab was not given during the first cycle to reduce the frequency and severity of infusion reactions. Filgrastim, sulfamethoxazole/trimethoprim, and acyclovir were administered prophylactically. The median age of the patients treated was 62 (range 44–80) and the median number of prior regimens was 2 (range 1–7). The overall frequency of response was 75% with 25% achieving a complete response, 3% a nodular response, and 47% a partial response. We have compared these results to the recently reported MD Anderson FCR regimen. In terms of pre-treatment characteristics the patient groups in both studies appear comparable with the exception of a higher proportion of high-risk patients treated with PCR (78%) compared to FCR (50%) (P=0.003). The response frequencies are virtually identical in both studies with responses seen 75% of PCR treated patients and 73% of FCR treated patients and CR achieved in 25% in both studies. In terms of toxicity, however, PCR compares favorably to FCR in the following categories: Grade 3/4 neutropenia PCR 53% vs FCR 81% (P=0.0007), thrombocytopenia PCR 16% vs FCR 34% (P=0.04), anemia PCR 9% vs FCR 24% (P=0.06), and grade 3/4 infections (including fever of unknown origin) PCR 28% vs FCR 47% (P=0.05). PCR also appeared to be better tolerated than FCR as indicated by the fraction of patients completing all planned cycles of chemotherapy at full dose 72% vs 38% (P=0.0004). An important caveat in these comparisons is that myeloid growth factor was routinely administered to patients on the PCR study but was not routinely administered to patients treated with FCR. In conclusion, PCR appears to be equivalent in activity to FCR but may be better tolerated and less toxic. These results indicate that a prospective randomized comparison is warranted.