Pentostatin and cyclophosphamide: An effective new regimen in previously treated patients with chronic lymphocytic leukemia Journal Article


Authors: Weiss, M. A.; Maslak, P. G.; Jurcic, J. G.; Scheinberg, D. A.; Aliff, T. B.; Lamanna, N.; Frankel, S. R.; Kossman, S. E.; Horgan, D.
Article Title: Pentostatin and cyclophosphamide: An effective new regimen in previously treated patients with chronic lymphocytic leukemia
Abstract: Purpose: Purine analogs and alkylators are important agents in the treatment of chronic lymphocytic leukemia (CLL). Previously, combinations of fludarabine and chlorambucil were abandoned because of increased toxicity from overlapping myelosuppression and immunosuppression. Of the purine analogs active in CLL, pentostatin may be least myelosuppressive. We hypothesized that combining pentostatin with cyclophosphamide would have less myelotoxicity than combinations using other purine analogs. Patients and Methods: We studied 23 patients with previously treated CLL. All patients received pentostatin 4 mg/ m2. Seventeen patients received cyclophosphamide 600 mg/m 2, and six patients received cyclophosphamide 900 mg/m2. Both drugs were administered on day 1 of each cycle, and cycles were repeated every 3 weeks for six treatments. Filgrastim, sulfamethoxazole/trimethoprim, and acyclovir were administered prophylactically. The median number of prior treatment regimens was three (range, one to five) with 13 patients (57%) refractory to prior fludarabine therapy. Results: The cyclophosphamide 900 mg/m2 dose level was associated with moderate to severe nausea, and we chose cyclophosphamide 600 mg/m2 as the dose for further study. There were 17 responses (74%; 95% confidence interval, 63% to 85%), including four complete responses. The response rate was 77% in fludarabine-refractory patients. Myelosuppression was acceptable with grade 3/4 neutropenia and thrombocytopenia, seen in 35% and 30% of patients, respectively. The relative sparing of thrombopoiesis can be seen in that only one patient (5%) with an initial platelet count of more than 20,000 required platelet transfusions while receiving therapy. Conclusion: Pentostatin 4 mg/m2 with cyclophosphamide 600 mg/m2 is safe and effective in previously treated patients with CLL. On the basis of these results, we are currently studying pentostatin, cyclophosphamide, and rituximab (PCR) therapy in patients with CLL. © 2003 by American Society of Clinical Oncology.
Keywords: adult; clinical article; controlled study; treatment outcome; aged; middle aged; fludarabine; neutropenia; drug efficacy; drug safety; unspecified side effect; antineoplastic agent; multiple cycle treatment; bone marrow; bone marrow suppression; blood toxicity; nausea; thrombocytopenia; antineoplastic combined chemotherapy protocols; drug administration schedule; aciclovir; cyclophosphamide; drug effect; drug resistance; chemically induced disorder; drug derivative; drug administration; recombinant granulocyte colony stimulating factor; antibiotics, antineoplastic; chronic lymphatic leukemia; antineoplastic antibiotic; cotrimoxazole; immunosuppressive agents; chlorambucil; pentostatin; immunosuppressive agent; vidarabine; thrombocyte transfusion; leukemia, lymphocytic, chronic; humans; human; male; female; priority journal; article
Journal Title: Journal of Clinical Oncology
Volume: 21
Issue: 7
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2003-04-01
Start Page: 1278
End Page: 1284
Language: English
DOI: 10.1200/jco.2003.08.100
PUBMED: 12663715
PROVIDER: scopus
DOI/URL:
Notes: Export Date: 12 September 2014 -- Source: Scopus
Altmetric Score
MSK Authors
  1. Nicole Lamanna
    57 Lamanna
  2. Timothy Aliff
    7 Aliff
  3. Joseph G Jurcic
    127 Jurcic
  4. Peter Maslak
    166 Maslak
  5. Mark Weiss
    80 Weiss
  6. Denise E Horgan
    9 Horgan