Phase II study of 2-chlorodeoxyadenosine in combination with chlorambucil in previously untreated B-cell chronic lymphocytic leukemia

Ayalew Tefferi, Ralph Levitt, Chin Yang Li, Georgene Schroeder, Loren K. Tschetter, John C. Michalak, James E. Krook, Thomas E. Witzig

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

The objective was to determine the safety and efficacy of adding a maximally tolerated dose of 2-chlorodeoxyadenosine (2-CdA) to standard chlorambucil (CLB) therapy in previously untreated B-cell chronic lymphocytic leukemia (CLL). Thirty patients with CLL (median age, 64 years) received two courses of 2-CdA given intravenously (2 mg/m2 daily for 7 days) added to biweekly administration of CLB at 30 mg/m2 given orally. The diagnosis of CLL, treatment indications, and response criteria were according to the National Cancer Institute established guidelines. Sixteen patients (53%) had advanced-stage disease, and four (13%) had trisomy 12 abnormality. The overall remission rate was 80%, including 20% complete remission (CR), 30% nodular partial remission (nPR), and 30% partial remission (PR). Minimal residual disease was detected phenotypically in two of five patients with CR and in eight of nine with nPR. Overall, CR, nPR, and PR rates were not influenced significantly by the presence of cytogenetic abnormalities or advanced clinical stage. With a median follow-up of 33 months, 58% of patients who had a response had relapse. Median time to progression in all 30 patients was 30 months, and time to progression and progression-free survival were not significantly different for the different response groups, clinical stages, or cytogenetic groups. Severe neutropenia and thrombocytopenia occurred in 33% and 7% of patients, respectively. Only two patients had documented bacterial infections, and four had herpetic infections. Concurrent combination chemotherapy with abbreviated doses of 2-CdA and standard-dose CLB is feasible and safe in previously untreated CLL. Antitumor activity may be superior to that of CLB alone given in conventional doses. Whether a different schedule of combining these two agents would result in improved outcome is being investigated.

Original languageEnglish (US)
Pages (from-to)509-516
Number of pages8
JournalAmerican Journal of Clinical Oncology: Cancer Clinical Trials
Volume22
Issue number5
DOIs
StatePublished - Oct 1999

Keywords

  • 2- Chlorodeoxyadenosine
  • B-cell chronic lymphocytic leukemia
  • Chemotherapy
  • Chlorambucil
  • Leukemia

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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