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

Stuart M. Lichtman, Constance T. Cirrincione, Arti Hurria, Aminah Jatoi, Maria Theodoulou, Antonio C. Wolff, Julie Gralow, Daniel E. Morganstern, Gustav Magrinat, Harvey Jay Cohen, Hyman B. Muss

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Purpose: 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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)699-705
Number of pages7
JournalJournal of Clinical Oncology
Volume34
Issue number7
DOIs
StatePublished - Mar 1 2016

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Breast Neoplasms
Creatinine
Kidney
Methotrexate
Cyclophosphamide
Renal Insufficiency
Fluorouracil
Clinical Trials
Therapeutics
Survival
Doxorubicin
Recurrence
Capecitabine
Incidence

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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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. / Lichtman, Stuart M.; Cirrincione, Constance T.; Hurria, Arti; Jatoi, Aminah; Theodoulou, Maria; Wolff, Antonio C.; Gralow, Julie; Morganstern, Daniel E.; Magrinat, Gustav; Cohen, Harvey Jay; Muss, Hyman B.

In: Journal of Clinical Oncology, Vol. 34, No. 7, 01.03.2016, p. 699-705.

Research output: Contribution to journalArticle

Lichtman, Stuart M. ; Cirrincione, Constance T. ; Hurria, Arti ; Jatoi, Aminah ; Theodoulou, Maria ; Wolff, Antonio C. ; Gralow, Julie ; Morganstern, Daniel E. ; Magrinat, Gustav ; Cohen, Harvey Jay ; Muss, Hyman B. / 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. In: Journal of Clinical Oncology. 2016 ; Vol. 34, No. 7. pp. 699-705.
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abstract = "Purpose: 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. Conclusion: 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.",
author = "Lichtman, {Stuart M.} and Cirrincione, {Constance T.} and Arti Hurria and Aminah Jatoi and Maria Theodoulou and Wolff, {Antonio C.} and Julie Gralow and Morganstern, {Daniel E.} and Gustav Magrinat and Cohen, {Harvey Jay} and Muss, {Hyman B.}",
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T1 - Effect of pretreatment renal function on treatment and clinical outcomes in the adjuvant treatment of older women with breast cancer

T2 - Alliance A171201, an ancillary study of CALGB/CTSU 49907

AU - Lichtman, Stuart M.

AU - Cirrincione, Constance T.

AU - Hurria, Arti

AU - Jatoi, Aminah

AU - Theodoulou, Maria

AU - Wolff, Antonio C.

AU - Gralow, Julie

AU - Morganstern, Daniel E.

AU - Magrinat, Gustav

AU - Cohen, Harvey Jay

AU - Muss, Hyman B.

PY - 2016/3/1

Y1 - 2016/3/1

N2 - Purpose: 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. Conclusion: 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.

AB - Purpose: 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. Conclusion: 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.

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