title: Pentostatin, cyclophosphamide, and rituximab is an active, well-tolerated regimen for patients with previously treated chronic lymphocytic leukemia.
abstract: OBJECTIVE
  Purine analogs and alkylators are important agents for treating chronic lymphocytic leukemia (CLL). Early studies combining fludarabine and chlorambucil were abandoned owing to increased toxicity from overlapping myelosuppression and immunosuppression. Of the purine analogs active in CLL, pentostatin appears to be the least myelosuppressive. We previously reported that pentostatin and cyclophosphamide (PC) is active and well-tolerated in patients with relapsed or refractory CLL. Subsequently, we added rituximab, and now report on this three-drug combination.
  
  
  METHODS
  We treated 46 patients with either previously treated CLL (32 patients) or other low-grade B-cell neoplasms (14 patients). Patients received pentostatin 4 mg/m2, cyclophosphamide 600 mg/m2, and rituximab 375 mg/m2 (PCR). All drugs were administered on the same day (rituximab omitted from cycle 1), and patients received six cycles at 3-week intervals. Filgrastim, sulfamethoxazole/trimethoprim, and acyclovir were administered prophylactically.
  
  
  RESULTS
  The median age was 62 years (range, 30 to 80 years). The median number of prior regimens was two (range, one to seven). For CLL patients, there were 24 responses (75%), including eight complete responses (25%). In fludarabine-refractory patients, 75% responded. Toxicity was acceptable, with grade 3/4 infections (including fever of unknown origin) in 28%. The regimen was well tolerated, with 72% of patients receiving the planned treatment at full dose.
  
  
  CONCLUSIONS
  PCR is safe and effective in previously treated patients with CLL. In comparison with our prior two-drug regimen, we find that rituximab did not seem to add significantly to the toxicity, but did appear to confer a survival advantage. Based on these results, we are currently studying PCR as initial therapy for patients with CLL.
authors.affiliation: Leukemia Service, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
authors.forename: Nicole
authors.initials: N
authors.lastname: Lamanna
authors.forename: Matt
authors.initials: M
authors.lastname: Kalaycio
authors.forename: Peter
authors.initials: P
authors.lastname: Maslak
authors.forename: Joseph G
authors.initials: JG
authors.lastname: Jurcic
authors.forename: Mark
authors.initials: M
authors.lastname: Heaney
authors.forename: Renier
authors.initials: R
authors.lastname: Brentjens
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Zelenetz
authors.forename: Denise
authors.initials: D
authors.lastname: Horgan
authors.forename: Alison
authors.initials: A
authors.lastname: Gencarelli
authors.forename: Katherine S
authors.initials: KS
authors.lastname: Panageas
authors.forename: David A
authors.initials: DA
authors.lastname: Scheinberg
authors.forename: Mark A
authors.initials: MA
authors.lastname: Weiss
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D058846:Antibodies, Monoclonal, Murine-Derived; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D015649:Pentostatin / Q000008:administration & dosage / Q000009:adverse effects; D000069283:Rituximab
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D015649:Pentostatin; D000069283:Rituximab; D003520:Cyclophosphamide