Effect of creatinine clearance on patterns of toxicity in older patients receiving adjuvant chemotherapy for breast cancer.
OBJECTIVE
A number of age-related physiological changes contribute to an increased risk of toxicity of cancer chemotherapy in the elderly. One of the most important of these changes is the progressive decline in renal function with aging. We sought to determine the association between calculated creatinine clearance (CL(CR)) and grade 3 or 4 toxicities during adjuvant chemotherapy in women > or =65 years of age with breast cancer.


METHODS
We identified 1405 patients > or =65 years of age who had been treated for primary invasive breast cancer at Memorial Sloan-Kettering Cancer Center between January 1998 and December 2000. Patients were included in this analysis if they had stage I-III breast cancer and had received adjuvant chemotherapy. Patients were excluded if they had a prior history of breast cancer or chemotherapy, or had no baseline creatinine value available for review.


RESULTS
The 126 patients who met our criteria had received either cyclophosphamide, methotrexate and fluorouracil (CMF) [n = 65, mean age 71, range 65-78] or an anthracycline-based regimen (n = 61, mean age 69, range 65-79). The majority of patients (97%) had a normal creatinine. CL(CR), as calculated by the Cockcroft-Gault and Jeliffe formulas, decreased with increasing age (increased age associated with decreased Cockcroft-Gault [p = 0.02]; increased age associated with decreased Jeliffe [p < 0.01]). In multivariate analysis, after controlling for age and co-morbidity, a CL(CR) <50 mL/min by the Cockcroft-Gault formula was associated with an increased risk of fever and neutropenia (odds ratio [OR] 3.60; 95% CI 1.00, 12.94; p = 0.05) and a CL(CR) <50 mL/min by the Jeliffe formula was associated with a trend towards an increased risk of fever and neutropenia (OR 3.30; 95% CI 0.91, 12.33; p = 0.07), grade 3 or 4 haematological toxicity (OR 2.43; 95% CI 0.90, 6.55; p = 0.08), and need for erythropoietin (OR 4.15; 95% CI 0.81, 2.99; p = 0.09). An increase in creatinine (as a continuous variable) was associated with a trend towards an increased risk of grade 3 or 4 haematological toxicity (OR 5.81; 95% CI 0.96, 35.33; p = 0.06).


CONCLUSIONS
In this cohort of older breast cancer patients, a decreased CL(CR) and increased creatinine was associated with an increased risk of fever and neutropenia or haematological toxicity. CL(CR) should be considered when determining chemotherapy dosage in the elderly.
Hurria
Arti
A
Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. hurriaa@mskcc.org
Hurria
Anju
A
Brogan
Kelly
K
Panageas
Katherine S
KS
Pearce
Carol
C
Norton
Larry
L
Jakubowski
Ann
A
Howard
Jane
J
Hudis
Clifford
C
D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D018943:Anthracyclines / Q000008:administration & dosage / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy*; D017024:Chemotherapy, Adjuvant; D003404:Creatinine / Q000097:blood / Q000493:pharmacokinetics*; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D013997:Time Factors
D018943:Anthracyclines; D003520:Cyclophosphamide; D003404:Creatinine; D005472:Fluorouracil; D008727:Methotrexate