title: Effect of Pretreatment Renal Function on Treatment and Clinical Outcomes in the Adjuvant Treatment of Older Women With Breast Cancer: Alliance A171201, an Ancillary Study of CALGB/CTSU 49907.
abstract: OBJECTIVE
  CALGB 49907 showed the superiority of standard therapy, which included either cyclophosphamide/doxorubicin (AC) or cyclophosphamide/methotrexate/fluorouracil over single-agent capecitabine in the treatment of patients age ≥ 65 with early-stage breast cancer. The treatment allowed dosing adjustments of methotrexate and capecitabine for pretreatment renal function. The purpose of the current analysis was to assess the relationship between pretreatment renal function and five end points: toxicity, dose modification, therapy completion, relapse-free survival, and overall survival.
  
  
  METHODS
  Pretreatment renal function was defined as creatinine clearance (CrCl) using the Cockcroft-Gault equation. Multivariable logistic and proportional hazards regression were used to model separately for each regimen the relationship between CrCl and the first three binary end points and the last two time-to-event end points, respectively, after adjusting for variables of prognostic importance.
  
  
  RESULTS
  Six hundred nineteen assessable patients were analyzed. The incidence of stage III (moderate) or stage IV (severe) renal dysfunction was 72%, 64%, and 75% for treatment with cyclophosphamide/methotrexate/fluorouracil, AC, and capecitabine, respectively. There was no relationship for any regimen between pretreatment renal function and the five end points. For AC, as CrCl increased, the odds of nonhematologic toxicity decreased (P = .008), whereas for capecitabine, as CrCl increased, the odds of experiencing toxicity of any type also increased (P = .035). Patients with renal insufficiency who received dose modifications were not at increased risk for complications compared with those who did not have renal insufficiency and received a full dose.
  
  
  CONCLUSIONS
  Excluding from clinical trials patients with renal insufficiency but good performance status on the basis of concern of excessive hematologic toxicity or poor outcomes may not be justified with appropriate dosing modifications. Results should be considered in the design of clinical trials for older patients.
authors.affiliation: Stuart M. Lichtman and Maria Theodoulou, Memorial Sloan Kettering Cancer Center, New York, NY; Constance T. Cirrincione, Duke University; Harvey Jay Cohen, Duke University Medical Center, Durham; Gustave Magrinat, Cone Health Cancer Center, Greensboro; Hyman B. Muss, University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, NC; Arti Hurria, City of Hope, Duarte, CA; Aminah Jatoi, Mayo Clinic, Rochester, MN; Antonio C. Wolff, The Johns Hopkins Kimmel Comprehensive Cancer Center, Baltimore, MD; Julie Gralow, Seattle Cancer Care Alliance, Seattle, WA; and Daniel E. Morganstern, Dana-Farber Cancer Institute, Boston, MA. lichtmas@mskcc.org.
authors.forename: Stuart M
authors.initials: SM
authors.lastname: Lichtman
authors.affiliation: Stuart M. Lichtman and Maria Theodoulou, Memorial Sloan Kettering Cancer Center, New York, NY; Constance T. Cirrincione, Duke University; Harvey Jay Cohen, Duke University Medical Center, Durham; Gustave Magrinat, Cone Health Cancer Center, Greensboro; Hyman B. Muss, University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, NC; Arti Hurria, City of Hope, Duarte, CA; Aminah Jatoi, Mayo Clinic, Rochester, MN; Antonio C. Wolff, The Johns Hopkins Kimmel Comprehensive Cancer Center, Baltimore, MD; Julie Gralow, Seattle Cancer Care Alliance, Seattle, WA; and Daniel E. Morganstern, Dana-Farber Cancer Institute, Boston, MA.
authors.forename: Constance T
authors.initials: CT
authors.lastname: Cirrincione
authors.affiliation: Stuart M. Lichtman and Maria Theodoulou, Memorial Sloan Kettering Cancer Center, New York, NY; Constance T. Cirrincione, Duke University; Harvey Jay Cohen, Duke University Medical Center, Durham; Gustave Magrinat, Cone Health Cancer Center, Greensboro; Hyman B. Muss, University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, NC; Arti Hurria, City of Hope, Duarte, CA; Aminah Jatoi, Mayo Clinic, Rochester, MN; Antonio C. Wolff, The Johns Hopkins Kimmel Comprehensive Cancer Center, Baltimore, MD; Julie Gralow, Seattle Cancer Care Alliance, Seattle, WA; and Daniel E. Morganstern, Dana-Farber Cancer Institute, Boston, MA.
authors.forename: Arti
authors.initials: A
authors.lastname: Hurria
authors.affiliation: Stuart M. Lichtman and Maria Theodoulou, Memorial Sloan Kettering Cancer Center, New York, NY; Constance T. Cirrincione, Duke University; Harvey Jay Cohen, Duke University Medical Center, Durham; Gustave Magrinat, Cone Health Cancer Center, Greensboro; Hyman B. Muss, University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, NC; Arti Hurria, City of Hope, Duarte, CA; Aminah Jatoi, Mayo Clinic, Rochester, MN; Antonio C. Wolff, The Johns Hopkins Kimmel Comprehensive Cancer Center, Baltimore, MD; Julie Gralow, Seattle Cancer Care Alliance, Seattle, WA; and Daniel E. Morganstern, Dana-Farber Cancer Institute, Boston, MA.
authors.forename: Aminah
authors.initials: A
authors.lastname: Jatoi
authors.affiliation: Stuart M. Lichtman and Maria Theodoulou, Memorial Sloan Kettering Cancer Center, New York, NY; Constance T. Cirrincione, Duke University; Harvey Jay Cohen, Duke University Medical Center, Durham; Gustave Magrinat, Cone Health Cancer Center, Greensboro; Hyman B. Muss, University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, NC; Arti Hurria, City of Hope, Duarte, CA; Aminah Jatoi, Mayo Clinic, Rochester, MN; Antonio C. Wolff, The Johns Hopkins Kimmel Comprehensive Cancer Center, Baltimore, MD; Julie Gralow, Seattle Cancer Care Alliance, Seattle, WA; and Daniel E. Morganstern, Dana-Farber Cancer Institute, Boston, MA.
authors.forename: Maria
authors.initials: M
authors.lastname: Theodoulou
authors.affiliation: Stuart M. Lichtman and Maria Theodoulou, Memorial Sloan Kettering Cancer Center, New York, NY; Constance T. Cirrincione, Duke University; Harvey Jay Cohen, Duke University Medical Center, Durham; Gustave Magrinat, Cone Health Cancer Center, Greensboro; Hyman B. Muss, University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, NC; Arti Hurria, City of Hope, Duarte, CA; Aminah Jatoi, Mayo Clinic, Rochester, MN; Antonio C. Wolff, The Johns Hopkins Kimmel Comprehensive Cancer Center, Baltimore, MD; Julie Gralow, Seattle Cancer Care Alliance, Seattle, WA; and Daniel E. Morganstern, Dana-Farber Cancer Institute, Boston, MA.
authors.forename: Antonio C
authors.initials: AC
authors.lastname: Wolff
authors.affiliation: Stuart M. Lichtman and Maria Theodoulou, Memorial Sloan Kettering Cancer Center, New York, NY; Constance T. Cirrincione, Duke University; Harvey Jay Cohen, Duke University Medical Center, Durham; Gustave Magrinat, Cone Health Cancer Center, Greensboro; Hyman B. Muss, University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, NC; Arti Hurria, City of Hope, Duarte, CA; Aminah Jatoi, Mayo Clinic, Rochester, MN; Antonio C. Wolff, The Johns Hopkins Kimmel Comprehensive Cancer Center, Baltimore, MD; Julie Gralow, Seattle Cancer Care Alliance, Seattle, WA; and Daniel E. Morganstern, Dana-Farber Cancer Institute, Boston, MA.
authors.forename: Julie
authors.initials: J
authors.lastname: Gralow
authors.affiliation: Stuart M. Lichtman and Maria Theodoulou, Memorial Sloan Kettering Cancer Center, New York, NY; Constance T. Cirrincione, Duke University; Harvey Jay Cohen, Duke University Medical Center, Durham; Gustave Magrinat, Cone Health Cancer Center, Greensboro; Hyman B. Muss, University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, NC; Arti Hurria, City of Hope, Duarte, CA; Aminah Jatoi, Mayo Clinic, Rochester, MN; Antonio C. Wolff, The Johns Hopkins Kimmel Comprehensive Cancer Center, Baltimore, MD; Julie Gralow, Seattle Cancer Care Alliance, Seattle, WA; and Daniel E. Morganstern, Dana-Farber Cancer Institute, Boston, MA.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Morganstern
authors.affiliation: Stuart M. Lichtman and Maria Theodoulou, Memorial Sloan Kettering Cancer Center, New York, NY; Constance T. Cirrincione, Duke University; Harvey Jay Cohen, Duke University Medical Center, Durham; Gustave Magrinat, Cone Health Cancer Center, Greensboro; Hyman B. Muss, University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, NC; Arti Hurria, City of Hope, Duarte, CA; Aminah Jatoi, Mayo Clinic, Rochester, MN; Antonio C. Wolff, The Johns Hopkins Kimmel Comprehensive Cancer Center, Baltimore, MD; Julie Gralow, Seattle Cancer Care Alliance, Seattle, WA; and Daniel E. Morganstern, Dana-Farber Cancer Institute, Boston, MA.
authors.forename: Gustav
authors.initials: G
authors.lastname: Magrinat
authors.affiliation: Stuart M. Lichtman and Maria Theodoulou, Memorial Sloan Kettering Cancer Center, New York, NY; Constance T. Cirrincione, Duke University; Harvey Jay Cohen, Duke University Medical Center, Durham; Gustave Magrinat, Cone Health Cancer Center, Greensboro; Hyman B. Muss, University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, NC; Arti Hurria, City of Hope, Duarte, CA; Aminah Jatoi, Mayo Clinic, Rochester, MN; Antonio C. Wolff, The Johns Hopkins Kimmel Comprehensive Cancer Center, Baltimore, MD; Julie Gralow, Seattle Cancer Care Alliance, Seattle, WA; and Daniel E. Morganstern, Dana-Farber Cancer Institute, Boston, MA.
authors.forename: Harvey Jay
authors.initials: HJ
authors.lastname: Cohen
authors.affiliation: Stuart M. Lichtman and Maria Theodoulou, Memorial Sloan Kettering Cancer Center, New York, NY; Constance T. Cirrincione, Duke University; Harvey Jay Cohen, Duke University Medical Center, Durham; Gustave Magrinat, Cone Health Cancer Center, Greensboro; Hyman B. Muss, University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, NC; Arti Hurria, City of Hope, Duarte, CA; Aminah Jatoi, Mayo Clinic, Rochester, MN; Antonio C. Wolff, The Johns Hopkins Kimmel Comprehensive Cancer Center, Baltimore, MD; Julie Gralow, Seattle Cancer Care Alliance, Seattle, WA; and Daniel E. Morganstern, Dana-Farber Cancer Institute, Boston, MA.
authors.forename: Hyman B
authors.initials: HB
authors.lastname: Muss
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D047072:Aromatase Inhibitors / Q000008:administration & dosage; D001943:Breast Neoplasms / Q000188:drug therapy*; D000069287:Capecitabine / Q000008:administration & dosage; D003404:Creatinine / Q000652:urine; D003520:Cyclophosphamide / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007677:Kidney Function Tests; D008727:Methotrexate / Q000008:administration & dosage; D011379:Prognosis; D051437:Renal Insufficiency / Q000139:chemically induced / Q000503:physiopathology*; D015996:Survival Rate; D013629:Tamoxifen / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D047072:Aromatase Inhibitors; D013629:Tamoxifen; D000069287:Capecitabine; D003520:Cyclophosphamide; D003404:Creatinine; D005472:Fluorouracil; D008727:Methotrexate