A Phase III trial of fludarabine, cyclophosphamide, and rituximab vs. pentostatin, cyclophosphamide, and rituximab in B-cell chronic lymphocytic leukemia

• Published in: Investigational new drugs 2012-06, Vol.30 (3), p.1232-1240
• Main Authors: Reynolds, Craig, Di Bella, Nicholas, Lyons, Roger M., Hyman, William, Richards, Donald A., Robbins, Gerald J., Vellek, Mark, Boehm, Kristi A., Zhan, Feng, Asmar, Lina
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal, Murine-Derived - administration & dosage; Antibodies, Monoclonal, Murine-Derived - adverse effects; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Cancer therapies; Cardiovascular disease; Chemotherapy; Creatinine; Cyclophosphamide - administration & dosage; Cyclophosphamide - adverse effects; Drug dosages; Female; Humans; Infections; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy; Male; Medicine; Medicine & Public Health; Middle Aged; Neutropenia; Oncology; Pentostatin - administration & dosage; Pentostatin - adverse effects; Pharmacology; Pharmacology/Toxicology; Phase III Studies; Radiation; Response rates; Rituximab; Side effects; Studies; Toxicity; Treatment Outcome; Vidarabine - administration & dosage; Vidarabine - adverse effects; Vidarabine - analogs & derivatives; Viral infections
• ISSN: 0167-6997; 1573-0646
• DOI: 10.1007/s10637-011-9737-y

Summary Background Uncontrolled studies comparing pentostatin (P), cyclophosphamide (C), and rituximab (R) (PCR) to fludarabine plus C+R (FCR) suggest similar efficacy with fewer infectious complications with PCR. We compared FCR and PCR in previously-untreated or minimally-treated B-cell chronic lymphocytic leukemia (CLL). Treatment FCR (F 20 mg/m 2 Days 1–5, C 600 mg/m 2 Day 1, R 375 mg/m 2 Day 1) (28-day cycles) or PCR (P 4 mg/m 2 Day 1, C 600 mg/m 2 Day 1, R 375 mg/m 2 Day 1) (21-day cycles). Dose 1 of R: 100 mg/m 2 was given on Day 8 Cycle 1 and the remainder on Day 9; in subsequent cycles the entire dose was given on Day 1. Results Ninety-two patients were randomly assigned to each group ( N  = 184). Groups were balanced; ~20% had received prior chemotherapy. The infection rate (FCR/PCR) was 31%/36%, the infective event rate was 38%/45%; 30 (35%)/37 (44%) patients were hospitalized; total hospitalization days was 271/404. 12 (14%)/6 (7%) patients achieved complete remissions (CR); the overall response rate (ORR) including CR+nodular PR (nPR)+PR was 59%/49%. Grade 3–4 treatment related AEs: neutropenia (69%/57%), leukopenia (34%/17%), thrombocytopenia (13%/6%). Grade 3–4 infections: febrile neutropenia (8%/6%), fever (2%/6%), infection (1%/3%), urinary tract infection (1%/0%), pneumonia (3%/1%), and sepsis (1%/2%); 5 deaths (1 FCR/4 PCR) were treatment-related. Conclusions PCR and FCR have significant activity in CLL and can be given safely in the community setting despite significant toxicity. ORRs were lower than expected; the CR rate was higher (NS) with FCR. This trial did not demonstrate a lower infection rate with PCR.