Pentostatin and cyclophosphamide

An effective new regimen in previously treated patients with chronic lymphocytic leukemia

Mark A. Weiss, Peter G. Maslak, Joseph G. Jurcic, David A. Scheinberg, Timothy B. Aliff, Nicole Lamanna, Stanley R. Frankel, Steven E. Kossman, Denise Horgan

Research output: Contribution to journalArticle

90 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1278-1284
Number of pages7
JournalJournal of Clinical Oncology
Volume21
Issue number7
DOIs
StatePublished - Apr 1 2003
Externally publishedYes

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Pentostatin
B-Cell Chronic Lymphocytic Leukemia
Cyclophosphamide
Therapeutics
Thrombopoiesis
Chlorambucil
Platelet Transfusion
Acyclovir
Alkylating Agents
Sulfamethoxazole Drug Combination Trimethoprim
Neutropenia
Platelet Count
Immunosuppression
Nausea

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Weiss, M. A., Maslak, P. G., Jurcic, J. G., Scheinberg, D. A., Aliff, T. B., Lamanna, N., ... Horgan, D. (2003). Pentostatin and cyclophosphamide: An effective new regimen in previously treated patients with chronic lymphocytic leukemia. Journal of Clinical Oncology, 21(7), 1278-1284. https://doi.org/10.1200/JCO.2003.08.100

Pentostatin and cyclophosphamide : An effective new regimen in previously treated patients with chronic lymphocytic leukemia. / Weiss, Mark A.; Maslak, Peter G.; Jurcic, Joseph G.; Scheinberg, David A.; Aliff, Timothy B.; Lamanna, Nicole; Frankel, Stanley R.; Kossman, Steven E.; Horgan, Denise.

In: Journal of Clinical Oncology, Vol. 21, No. 7, 01.04.2003, p. 1278-1284.

Research output: Contribution to journalArticle

Weiss, MA, Maslak, PG, Jurcic, JG, Scheinberg, DA, Aliff, TB, Lamanna, N, Frankel, SR, Kossman, SE & Horgan, D 2003, 'Pentostatin and cyclophosphamide: An effective new regimen in previously treated patients with chronic lymphocytic leukemia', Journal of Clinical Oncology, vol. 21, no. 7, pp. 1278-1284. https://doi.org/10.1200/JCO.2003.08.100
Weiss, Mark A. ; Maslak, Peter G. ; Jurcic, Joseph G. ; Scheinberg, David A. ; Aliff, Timothy B. ; Lamanna, Nicole ; Frankel, Stanley R. ; Kossman, Steven E. ; Horgan, Denise. / Pentostatin and cyclophosphamide : An effective new regimen in previously treated patients with chronic lymphocytic leukemia. In: Journal of Clinical Oncology. 2003 ; Vol. 21, No. 7. pp. 1278-1284.
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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.",
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AU - Scheinberg, David A.

AU - Aliff, Timothy B.

AU - Lamanna, Nicole

AU - Frankel, Stanley R.

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