Adjusted Adjuvant Chemotherapy Feasible For Older Renal Dysfunction Breast Cancer Patients

Renal dysfunction is not necessarily a contraindication for breast cancer adjuvant chemotherapy in older women

medwireNews: Chemotherapy for early-stage breast cancer is feasible in older women with renal dysfunction, suggest results from an ancillary study of a trial comparing standard chemotherapy regimens with capecitabine .

Complications associated with cyclophosphamide /doxorubicin (AC), cyclophosphamide/methotrexate /fluorouracil or capecitabine were no more likely in women with moderate or severe renal dysfunction than those without when doses were adjusted appropriately.

And there was no significant relationship between pretreatment renal function and the need for dose modification or the likelihood of treatment completion, the researchers report in the Journal of Clinical Oncology.

Nor was there a relation between baseline renal function and median relapse-free survival or overall survival.

“The general exclusion of patients with renal insufficiency from studies may not be justified, particularly if the drug of interest does not have renal excretion as its primary mechanism of elimination”, say Stuart Lichtman, from Memorial Sloan Kettering Cancer Center in New York, USA, and co-authors.

The 619 patients included in the study were aged 65 years or older and had a creatinine clearance rate (CrCl) of at least 30 mL/minute, as calculated by a modified form of the Cockcroft–Gault equation.

In all, 64% of patients given AC had moderate or severe renal dysfunction, as did 72% of patients given cyclophosphamide/methotrexate/fluorouracil and 75% given capecitabine. Dose modifications were made during the course of treatment using the CrCl and their body weight, the researchers explain.

For patients given AC, there was a significant correlation between increasing CrCl and a reduced likelihood of experiencing at least one non-haematological toxicity, with each 10-unit increase in CrCl giving a 31% decrease.

However, among capecitabine-treated patients there was a significant correlation between increasing CrCl and an increased risk of non-haematological toxicity, so that each 10-unit increase gave a 21% increase in the likelihood of at least one non-haematological adverse event.

“This unusual finding occurred because 26% of patients with higher CrCl (early renal function level 1 and 2) experienced grade ≥ 3 rash (hand-foot reaction) compared with 12% of patients with lower CrCl (late renal function level 3 and 4)”, the researchers explain.

Stuart Lichtman et al observe that the exclusion of patients with renal dysfunction has “unnecessarily decreased the already low participation of older patients in studies.”

Suggesting that their results can “provide guidance and some reassurance” to clinicians treating older patients, who have a higher incidence of renal dysfunction, they emphasize the need to determine CrCl before chemotherapy begins.

“Clinical trial design, data reporting, and treatment guidelines need to emphasize these factors”, they write.


Lichtman SM, Cirrincione CT, Hurria A, et al. 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. J Clin Oncol 2016; Advance online publication 11 January. doi: 10.1200/JCO.2015.62.6341

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