Phase II study of cladribine and cyclophosphamide in patients with chronic lymphocytic leukemia and prolymphocytic leukemia.
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/m(2)/day and cyclophosphamide 350 mg/m(2)/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.
Montillo
Marco
M
Department of Oncology/Haematology, Division of Haematology, Niguarda Ca' Granda Hospital, Piazza dell'Ospedale Maggiore 3, 20161 Milan, Italy. m.montillo@tiscali.it
Tedeschi
Alessandra
A
O'Brien
Susan
S
Di Raimondo
Francesco
F
Lerner
Susan
S
Ferrajoli
Alessandra
A
Morra
Enrica
E
Keating
Michael J
MJ
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D017338:Cladribine / Q000008:administration & dosage; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy*; D015463:Leukemia, Prolymphocytic / Q000188:drug therapy*; D007970:Leukopenia / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009503:Neutropenia / Q000139:chemically induced; D016879:Salvage Therapy; D013921:Thrombocytopenia / Q000139:chemically induced; D016896:Treatment Outcome
D017338:Cladribine; D003520:Cyclophosphamide