TY - JOUR
T1 - Phase II study of cladribine and cyclophosphamide in patients with chronic lymphocytic leukemia and prolymphocytic leukemia
AU - Montillo, Marco
AU - Tedeschi, Alessandra
AU - O'Brien, Susan
AU - Di Raimondo, Francesco
AU - Lerner, Susan
AU - Ferrajoli, Alessandra
AU - Morra, Enrica
AU - Keating, Michael J.
PY - 2003/1/1
Y1 - 2003/1/1
N2 - BACKGROUND. One of the mechanisms of action of cladribine is the inhibition of DNA repair of damage caused by radiation, alkylating agents, or other drugs. To determine its antitumor activity in combination with cyclophosphamide, we initiated a Phase II trial of the two agents in patients with advanced chronic lymphocytic leukemia (CLL) or prolymphocytic leukemia (PLL). METHODS. Twenty-nine patients with refractory or recurrent CLL or PLL received cladribine 4 mg/m2/day and cyclophosphamide 350 mg/m2/day (both administered intravenously) for 3 days every 4 weeks. RESULTS. Eleven patients (38%), nine with CLL and two with PLL, had a response. The median duration of response was 12 months. Severe extrahematologic toxicity (National Cancer Institute Grade 3-4) occurred in two patients, consisting of skin rash in one patient and progressive multifocal leukoencephalopathy in the other. The most common form of hematologic toxicity was severe neutropenia, which developed after 25% of the 84 courses was administered. Severe thrombocytopenia and anemia developed after 12% and 7% of the courses, respectively, and five episodes of anemia were immunomediated. In addition, three major infections resulted in the death of one patient. CONCLUSIONS. Although inferior to the combination fludarabine plus cyclophosphamide, this regimen showed interesting activity in patients with advanced CLL or PLL. Myelosuppression was the major dose-limiting toxic effect.
AB - BACKGROUND. One of the mechanisms of action of cladribine is the inhibition of DNA repair of damage caused by radiation, alkylating agents, or other drugs. To determine its antitumor activity in combination with cyclophosphamide, we initiated a Phase II trial of the two agents in patients with advanced chronic lymphocytic leukemia (CLL) or prolymphocytic leukemia (PLL). METHODS. Twenty-nine patients with refractory or recurrent CLL or PLL received cladribine 4 mg/m2/day and cyclophosphamide 350 mg/m2/day (both administered intravenously) for 3 days every 4 weeks. RESULTS. Eleven patients (38%), nine with CLL and two with PLL, had a response. The median duration of response was 12 months. Severe extrahematologic toxicity (National Cancer Institute Grade 3-4) occurred in two patients, consisting of skin rash in one patient and progressive multifocal leukoencephalopathy in the other. The most common form of hematologic toxicity was severe neutropenia, which developed after 25% of the 84 courses was administered. Severe thrombocytopenia and anemia developed after 12% and 7% of the courses, respectively, and five episodes of anemia were immunomediated. In addition, three major infections resulted in the death of one patient. CONCLUSIONS. Although inferior to the combination fludarabine plus cyclophosphamide, this regimen showed interesting activity in patients with advanced CLL or PLL. Myelosuppression was the major dose-limiting toxic effect.
KW - CLL
KW - Cladribine
KW - Cyclophosphamide
KW - PLL
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U2 - 10.1002/cncr.11000
DO - 10.1002/cncr.11000
M3 - Article
C2 - 12491512
AN - SCOPUS:0037214931
SN - 0008-543X
VL - 97
SP - 114
EP - 120
JO - Cancer
JF - Cancer
IS - 1
ER -