Purpose: 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. Methods: We evaluated 192 patients with previously untreated B-cell CLL who were entered onto the fludarabine treatment arm (25 mg/m2 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 (CrClest) was estimated using serum creatinine, age and body mass index. Results: The median age was 64 years (range 37-87 years) and median CrClest 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 CrClest and the time-to-toxicity endpoint. Patients with CrClest below 80 ml/min had increased incidence of toxicity during their treatment course (P<0.0001). Pretreatment anemia, thrombocytopenia and Rai stage were highly associated with the incidence of neutrophil toxicity and grade III/IV hematologic toxicities during the first cycle of treatment (P<0.0001). Conclusions: Patient age was not an independent risk factor for fludarabine-related toxicity, but CrClest was associated with time to toxicity.
|Original language||English (US)|
|Number of pages||9|
|Journal||Cancer chemotherapy and pharmacology|
|State||Published - 2002|
Bibliographical noteFunding Information:
This work was supported by an unrestricted educational grant from Berlex Laboratories, Richmond, CA.
R.E.M. was supported by the John A. Hartford Foundation and by the National Institutes of Healt h grant no. 5T32AG00029.
- Chronic lymphocytic leukemia
- Drug toxicity
- Kidney function tests