Pentostatin, chlorambucil and prednisone therapy for B-chronic lymphocytic leukemia: A phase I/II study by the Eastern Cooperative Oncology Group study E1488

Martin M. Oken, Sandra Lee, Neil Elliot Kay, William Knospe, Peter A. Cassileth

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Pentostatin is a purine nucleoside analog with demonstrated activity in low-grade lymphoid malignancies. The purpose of this study was to determine the dose of pentostatin (dCF) that could be combined with chlorambucil and prednisone to treat chronic lymphocytic leukemia (CLL), evaluate the toxicity of the resulting regimen and to estimate its efficacy. This was a multi-institutional Eastern Cooperative Oncology Group (ECOG) phase I-II study. Individuals with active B-CLL were eligible if they had no prior treatment or were in sensitive first relapse, provided they had normal renal and hepatic function. Pentostatin was evaluated in combination with orally administered chlorambucil 30 mg/m2 and prednisone 80 mg/day, 1-5 of each 14-day cycle. The pentostatin dose was 2 mg/m2 IV, day 1 for the first 6 patients; 3 mg/m2 IV, day 1 for the next 6 patients; and 4 mg/m2 IV, day 1 for the last set of 6 patients. Fifty-five patients were entered. Because of increasing toxicity with no apparent improvement in clinical efficacy on escalation of the pentostatin dose, 2 mg/m2 was chosen as the phase II dose, and 43 patients were treated at this level. Thirty-nine of these patients were eligible, of which 38 were evaluable for response, 36 of these 38 had no prior treatment. Complete response (CR) manifested by normal bone marrow morphology, peripheral blood counts and resolution of any lymphadenopathy or hepatosplenomegaly occurred in 17 patients (45%). The overall objective response rate was 87%. The median response duration was 33 months and the median survival 5 years. The median time to treatment failure is 32 months. Severe (Grade 3+) infections were seen in 31% of patients and included bacterial pneumonia (n = 4), Pneumocystis pneumonia (n = 1), fungal pneumonia (n = 2), urinary tract infection with sepsis (n = 1) and Herpes Zoster (n = 5). Overall, 11 patients had H. Zoster while on study. Due to toxicity, 33% of patients stopped therapy. Pentostatin, chlorambucil and prednisone is a highly active regimen in CLL but cannot be recommended in present form because of an unacceptable incidence of opportunistic infections. These findings add to other recent reports which suggest combination therapy with pentostatin and alkylators are active in B-CLL. However, these combination chemotherapies will need to be combined with appropriate addition of anti-bacterial and anti-viral prophylaxis to reduce infection risk for B-CLL patients.

Original languageEnglish (US)
Pages (from-to)79-84
Number of pages6
JournalLeukemia and Lymphoma
Volume45
Issue number1
DOIs
StatePublished - Jan 2004

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Pentostatin
Chlorambucil
B-Cell Chronic Lymphocytic Leukemia
Prednisone
Therapeutics
Herpes Zoster
Purine Nucleosides
Bacterial Pneumonia
Pneumocystis Pneumonia
Alkylating Agents
Opportunistic Infections
Infection
Combination Drug Therapy
Treatment Failure
Urinary Tract Infections
Sepsis
Pneumonia

Keywords

  • Alkylators
  • B-CLL
  • Combination therapy
  • Pentostatin

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Pentostatin, chlorambucil and prednisone therapy for B-chronic lymphocytic leukemia : A phase I/II study by the Eastern Cooperative Oncology Group study E1488. / Oken, Martin M.; Lee, Sandra; Kay, Neil Elliot; Knospe, William; Cassileth, Peter A.

In: Leukemia and Lymphoma, Vol. 45, No. 1, 01.2004, p. 79-84.

Research output: Contribution to journalArticle

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abstract = "Pentostatin is a purine nucleoside analog with demonstrated activity in low-grade lymphoid malignancies. The purpose of this study was to determine the dose of pentostatin (dCF) that could be combined with chlorambucil and prednisone to treat chronic lymphocytic leukemia (CLL), evaluate the toxicity of the resulting regimen and to estimate its efficacy. This was a multi-institutional Eastern Cooperative Oncology Group (ECOG) phase I-II study. Individuals with active B-CLL were eligible if they had no prior treatment or were in sensitive first relapse, provided they had normal renal and hepatic function. Pentostatin was evaluated in combination with orally administered chlorambucil 30 mg/m2 and prednisone 80 mg/day, 1-5 of each 14-day cycle. The pentostatin dose was 2 mg/m2 IV, day 1 for the first 6 patients; 3 mg/m2 IV, day 1 for the next 6 patients; and 4 mg/m2 IV, day 1 for the last set of 6 patients. Fifty-five patients were entered. Because of increasing toxicity with no apparent improvement in clinical efficacy on escalation of the pentostatin dose, 2 mg/m2 was chosen as the phase II dose, and 43 patients were treated at this level. Thirty-nine of these patients were eligible, of which 38 were evaluable for response, 36 of these 38 had no prior treatment. Complete response (CR) manifested by normal bone marrow morphology, peripheral blood counts and resolution of any lymphadenopathy or hepatosplenomegaly occurred in 17 patients (45{\%}). The overall objective response rate was 87{\%}. The median response duration was 33 months and the median survival 5 years. The median time to treatment failure is 32 months. Severe (Grade 3+) infections were seen in 31{\%} of patients and included bacterial pneumonia (n = 4), Pneumocystis pneumonia (n = 1), fungal pneumonia (n = 2), urinary tract infection with sepsis (n = 1) and Herpes Zoster (n = 5). Overall, 11 patients had H. Zoster while on study. Due to toxicity, 33{\%} of patients stopped therapy. Pentostatin, chlorambucil and prednisone is a highly active regimen in CLL but cannot be recommended in present form because of an unacceptable incidence of opportunistic infections. These findings add to other recent reports which suggest combination therapy with pentostatin and alkylators are active in B-CLL. However, these combination chemotherapies will need to be combined with appropriate addition of anti-bacterial and anti-viral prophylaxis to reduce infection risk for B-CLL patients.",
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