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.
OBJECTIVE
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/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.


RESULTS
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<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 CrCl(est) was associated with time to toxicity.
Geriatrics Research, Education and Clinical Center, Veterans Affairs Medical Center and Hematology/Oncology Division, Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
Robert E
RE
Martell
Bercedis L
BL
Peterson
Harvey Jay
HJ
Cohen
William P
WP
Petros
Kanti R
KR
Rai
Vicki A
VA
Morrison
Laurence
L
Elias
Lois
L
Shepherd
John
J
Hines
Richard A
RA
Larson
Charles A
CA
Schiffer
Herbert I
HI
Hurwitz
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects*; D015992:Body Mass Index; D003404:Creatinine / Q000097:blood*; D018572:Disease-Free Survival; D005260:Female; D006403:Hematologic Tests; D006801:Humans; D007677:Kidney Function Tests; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood / Q000188:drug therapy*; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009504:Neutrophils / Q000187:drug effects; D014740:Vidarabine / Q000009:adverse effects* / Q000031:analogs & derivatives
D000970:Antineoplastic Agents; D003404:Creatinine; D014740:Vidarabine; C024352:fludarabine