TY - JOUR
T1 - Phase I study of combined 2-chlorodeoxyadenosine and chlorambucil in chronic lymphoid leukemia and low-grade lymphoma
AU - Tefferi, Ayalew
AU - Witzig, Thomas E.
AU - Reid, Joel M.
AU - Li, Chin Yang
AU - Ames, Matthew M.
PY - 1994/3
Y1 - 1994/3
N2 - Purpose: We conducted a dose-escalation study of 2-chlorodeoxyadenosine (2-CdA) added to a standard fixed dose of chlorambucil to evaluate the toxicity of the combined regimen in patients with chronic lymphocytic leukemia (CLL) and low-grade lymphoma. Patients and Methods: A total of 15 adults with relapsed or refractory CLL or low-grade lymphoma were to receive chlorambucil orally (30 mg/m2) every 2 weeks. Also, groups of three patients were to receive escalating doses of continuous intravenously administered 2- CdA at 1, 2, or 4 mg/m2/d for 7 days repeated at monthly intervals. All patients had pharmacokinetic studies during the first cycle of 2-CdA therapy; the results were compared with other institutional phase I studies in which comparable amounts of 2-CdA were administered by bolus infusion for 5 days. Results: The maximal-tolerated dose of 2-CdA that could be combined with chlorambucil was 2 mg/m2/d for 7 days for a maximum of two courses. At a higher dose level of 2-CdA or at the maximal-tolerated dose level given for more than two courses, severe and protracted pancytopenia, sometimes associated with life-threatening infections, was noted. Nonhematologic toxicities were limited to moderate degrees of nausea, vomiting, anorexia, and fatigue. Results of the pharmacologic studies suggested that 2-CdA clearance was independent of administration schedule and was unaffected by concomitant administration of chlorambucil. Conclusion: These observations suggest the possibility of combining two cycles of continuous intravenously administered 2-CdA (2 mg/m2/d for 7 days) with standard doses of oral chlorambucil to test the efficacy of the combination regimen in phase II trials.
AB - Purpose: We conducted a dose-escalation study of 2-chlorodeoxyadenosine (2-CdA) added to a standard fixed dose of chlorambucil to evaluate the toxicity of the combined regimen in patients with chronic lymphocytic leukemia (CLL) and low-grade lymphoma. Patients and Methods: A total of 15 adults with relapsed or refractory CLL or low-grade lymphoma were to receive chlorambucil orally (30 mg/m2) every 2 weeks. Also, groups of three patients were to receive escalating doses of continuous intravenously administered 2- CdA at 1, 2, or 4 mg/m2/d for 7 days repeated at monthly intervals. All patients had pharmacokinetic studies during the first cycle of 2-CdA therapy; the results were compared with other institutional phase I studies in which comparable amounts of 2-CdA were administered by bolus infusion for 5 days. Results: The maximal-tolerated dose of 2-CdA that could be combined with chlorambucil was 2 mg/m2/d for 7 days for a maximum of two courses. At a higher dose level of 2-CdA or at the maximal-tolerated dose level given for more than two courses, severe and protracted pancytopenia, sometimes associated with life-threatening infections, was noted. Nonhematologic toxicities were limited to moderate degrees of nausea, vomiting, anorexia, and fatigue. Results of the pharmacologic studies suggested that 2-CdA clearance was independent of administration schedule and was unaffected by concomitant administration of chlorambucil. Conclusion: These observations suggest the possibility of combining two cycles of continuous intravenously administered 2-CdA (2 mg/m2/d for 7 days) with standard doses of oral chlorambucil to test the efficacy of the combination regimen in phase II trials.
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U2 - 10.1200/JCO.1994.12.3.569
DO - 10.1200/JCO.1994.12.3.569
M3 - Article
C2 - 8120555
AN - SCOPUS:0028231835
SN - 0732-183X
VL - 12
SP - 569
EP - 574
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 3
ER -