No Need to Exclude Patients With Renal Insufficiency From Clinical Trials
Excluding patients with renal insufficiency but good performance status from clinical trials due to concern of excessive hematologic toxicity or poor outcomes may not be necessary with appropriate dosing modifications, based on a report published online before print in the Journal of Clinical Oncology.1
CALGB 49907 demonstrated the superiority of standard therapy for patients age 65 years and older with early stage breast cancer. Standard therapy was described as cyclophosphamide/doxorubicin (AC) or cyclophosphamide/methotrexate/fluorouracil over capecitabine as a single agent, and dosing adjustments of methotrexate and capecitabine for pretreatment renal function were allowed.
In this analysis, the investigators sought to assess the relationship between pretreatment renal function and 5 end points: toxicity, dose modification, therapy completion, relapse-free survival, and overall survival. Renal function was defined as creatinine clearance (CrCl) using the Cockcroft-Gault equation. The researchers analyzed 619 assessable patients.
Incidence of moderate (stage III) or severe (stage IV) renal dysfunction was 72% in the cyclophosphamide/methotrexate/fluorouracil arm; 64% in the AC arm; and 75% in the capecitabine arm. No relationship was seen between pretreatment renal function and the 5 end points with any of the regimens. However, risk of nonhematologic toxicity decreased as CrCl increased (P=.008), whereas risk of any type of toxicity increased with increasing CrCl (P=.035).
In addition, risk for complications were not increased in patients who received dose modifications due to renal insufficiency compared with those who did not have renal insufficiency and received a full dose.
The researchers conclude that these results should be considered in the design of clinical trials for older patients.
1. 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 [published online ahead of print January 11, 2016]. J Clin Oncol. doi:10.1200/JCO.2015.62.6341.