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.

Abstract

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/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.

• Authors: Robert E Martell, Bercedis L Peterson, Harvey Jay Cohen, William P Petros, Kanti R Rai, Vicki A Morrison, Laurence Elias, Lois Shepherd, John Hines, Richard A Larson, Charles A Schiffer, Herbert I Hurwitz
• Journal: Cancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 50 Issue 1 Pg. 37-45 (Jul 2002) ISSN: 0344-5704 [Print] Germany
• PMID: 12111110 (Publication Type: Clinical Trial, Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antineoplastic Agents
• Creatinine
• Vidarabine
• fludarabine

Topics

• Adult
• Age Factors
• Aged
• Aged, 80 and over
• Antineoplastic Agents (adverse effects)
• Body Mass Index
• Creatinine (blood)
• Disease-Free Survival
• Female
• Hematologic Tests
• Humans
• Kidney Function Tests
• Leukemia, Lymphocytic, Chronic, B-Cell (blood, drug therapy)
• Leukocyte Count
• Male
• Middle Aged
• Neoplasm Staging
• Neutrophils (drug effects)
• Vidarabine (adverse effects, analogs & derivatives)