Little Effect of Pretreatment Renal Function on Outcomes in Older Women Receiving Chemotherapy for Early-Stage Breast Cancer
As reported by Lichtman et al in the Journal of Clinical Oncology, an ancillary study (Alliance A171201) of the CALGB 49907 trial showed no significant association of pretreatment creatinine clearance with grade ≥ 3 hematologic toxicity, dose modification, therapy completion, relapse-free survival, or overall survival in women aged ≥ 65 years with early-stage breast cancer receiving adjuvant cyclophosphamide/doxorubicin, cyclophosphamide/methotrexate/fluorouracil, or single-agent capecitabine. CALGB 49907, which showed the superiority of standard adjuvant therapy over single-agent capecitabine in this setting, allowed dose adjustments of methotrexate and capecitabine based on pretreatment renal function.
Study Details
In the ancillary study, the outcomes were assessed in 619 women based on pretreatment renal function, defined as creatinine clearance using the Cockcroft-Gault equation. Stage III or IV renal dysfunction was present at baseline in 72% of the cyclophosphamide/methotrexate/fluorouracil group, 64% of the cyclophosphamide/doxorubicin group, and 75% of the capecitabine group.
Absence of Significant Relationships
No significant relationship was observed between baseline renal function and any treatment regimen for hematologic toxicity, dose modification, therapy completion, or relapse-free or overall survival. Risk of grade ≥ 3 nonhematologic toxicity was decreased with increasing creatinine clearance for cyclophosphamide/doxorubicin (odds ratio [OR] = 0.69, P = .008, for 10-unit increase) and borderline significantly increased for capecitabine (OR = 1.21, P = .052, for 10-unit increase); risk of hematologic or nonhematologic toxicity was increased with increasing creatinine clearance for capecitabine (OR = 1.23, P = .035, per 10-unit increase). No increased risk of complications was observed for patients with renal insufficiency who received dose modifications vs patients without renal insufficiency who received full doses.
The investigators concluded: “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.”
The study was supported by the National Cancer Institute and Alliance for Clinical Trials in Oncology.
Stuart M. Lichtman, MD, of Memorial Sloan Kettering Cancer Center, is the corresponding author of the Journal of Clinical Oncology article.
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