Effect of creatinine clearance on patterns of toxicity in older patients receiving adjuvant chemotherapy for breast cancer Journal Article


Authors: Hurria, A.; Brogan, K.; Panageas, K. S.; Pearce, C.; Norton, L.; Jakubowski, A.; Howard, J.; Hudis, C.
Article Title: Effect of creatinine clearance on patterns of toxicity in older patients receiving adjuvant chemotherapy for breast cancer
Abstract: 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. DESIGN AND 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.
Keywords: aged; aged, 80 and over; retrospective studies; fluorouracil; chemotherapy, adjuvant; methotrexate; antineoplastic agent; antineoplastic combined chemotherapy protocols; creatinine; cyclophosphamide; age factors; breast neoplasms; retrospective study; time; time factors; age; blood; chemically induced disorder; adjuvant chemotherapy; breast tumor; prediction and forecasting; predictive value of tests; anthracycline; anthracyclines; hematologic disease; cmf regimen; hematologic diseases
Journal Title: Drugs & Aging
Volume: 22
Issue: 9
ISSN: 1170-229X
Publisher: Adis International Ltd  
Date Published: 2005-01-01
Start Page: 785
End Page: 791
Language: English
PUBMED: 16156682
PROVIDER: scopus
DOI/URL:
Notes: --- - "Cited By (since 1996): 9" - "Export Date: 24 October 2012" - "Source: Scopus"
Citation Impact
MSK Authors
  1. Clifford Hudis
    905 Hudis
  2. Larry Norton
    758 Norton
  3. Arti Hurria
    36 Hurria
  4. Katherine S Panageas
    512 Panageas
  5. Jane E Howard
    23 Howard
  6. Carol Pearce
    5 Pearce