Dose-escalation trial of cladribine using five daily intravenous infusions in patients with advanced hematologic malignancies

J Clin Oncol. 1996 Jan;14(1):188-95. doi: 10.1200/JCO.1996.14.1.188.


Purpose: The optimal dose and schedule for cladribine (2CdA) therapy of malignant hematologic diseases have not been determined. This dose-escalation study was designed to assess toxicity when 2CdA is given using five daily 1-hour intravenous infusions.

Patients and methods: Forty-two adults with advanced hematologic malignancies were treated in one of nine cohorts, starting at 2.5 mg/m2/d for 5 days. Plasma drug concentrations were measured by high-performance liquid chromatography. Responses were assessed by bone marrow biopsy on day 15 of the first course and by clinical measurements after each course. Patients received one to four courses each.

Results: Nonhematologic toxicity was mild, and dose-limiting nonhematologic toxicity was not observed, even at the highest dose level of 21.5 mg/m2/d. In particular, neurotoxicity was not observed. The maximum-tolerated dose (MTD) was not identified. However, prolonged cytopenias and severe infections were more common in the higher 2CdA dose cohorts. Logistic regression analysis suggested that severe hematologic toxicity was associated with pretreatment platelet count and performance status (PS). Good-risk patients were identified as having a PS of 0 and platelet count > or = 80,000/microL, PS of 1 and platelet count > or = 120,000/microL, or PS of 2 and platelet count > or = 160,000/microL. Sustained complete responses (CRs) and partial responses (PRs) were observed in eight patients.

Conclusion: 2CdA can be administered using five daily 1-hour infusions at 21.5 mg/m2/d without dose-limiting nonhematologic toxicity. Unlike continuous intravenous infusions, neurotoxicity was not observed using this schedule. Further dose escalation may be possible in good PS patients with adequate platelet counts.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / toxicity
  • Bone Marrow / drug effects
  • Chi-Square Distribution
  • Cladribine / administration & dosage*
  • Cladribine / toxicity
  • Diarrhea / chemically induced
  • Digestive System Diseases / chemically induced
  • Drug Administration Schedule
  • Fatigue / chemically induced
  • Female
  • Fever / chemically induced
  • Hematologic Diseases / chemically induced
  • Humans
  • Immunocompromised Host
  • Infections / immunology
  • Infusions, Intravenous
  • Logistic Models
  • Lymphoproliferative Disorders / drug therapy*
  • Lymphoproliferative Disorders / immunology
  • Male
  • Middle Aged
  • Treatment Outcome


  • Antineoplastic Agents
  • Cladribine