Analysis of age, estimated creatinine clearance and pretreatment hematologic parameters as predictors of fludarabine toxicity in patients treated for chronic lymphocytic leukemia: a CALGB (9011) coordinated intergroup study

Fludarabine is a renally excreted agent that is an effective treatment for chronic lymphocytic leukemia (CLL), a disease predominantly of the elderly. We sought to determine whether age, renal function or pretreatment hematologic status predicted toxicity of fludarabine treatment for CLL. We evaluated 192 patients with previously untreated B-cell CLL who were entered onto the fludarabine treatment arm (25 mg/m(2) daily for 5 days every 28 days) of CALGB study 9011, an intergroup study with participation from SWOG, CTG/NCI-C and ECOG. Patients were required to have serum creatinine within 1.5 times normal. Hematologic indices and infections were recorded during the first 28-day cycle of treatment. A time-to-toxicity endpoint was evaluated over the entire course of fludarabine treatment. Creatinine clearance (CrCl(est)) was estimated using serum creatinine, age and body mass index. The median age was 64 years (range 37-87 years) and median CrCl(est) was 62 ml/min (range 27-162 ml/min, interquartile range 52-79 ml/min). We found no association between age and incidence of hematologic toxicity or infection during the first cycle of treatment. There was a strong association between CrCl(est) and the time-to-toxicity endpoint. Patients with CrCl(est) below 80 ml/min had increased incidence of toxicity during their treatment course ( P