Is measurement of total body nitrogen (TBN) a useful predictor of chemotherapy (C/T) toxicity in breast cancer?

Abstract

Controversy exists as to reliance on body surface area in determining C/T dose, particularly with obese patients. Measurement of TBN has been suggested as a more accurate predictor of clinical course and prognosis in serious illness. We tested the hypothesis that a depletion of TBN may also be associated with increased toxicity in patients receiving standard CMF (Cyclophosphamide, Methotrexate, 5-Fluorouracil) C/T for breast cancer. Absolute neutrophil count nadir (ANCN) was used as a measure of toxicity. 26 patients with breast adenocarcinoma had serial measurements of TBN, whilst receiving intravenous CMF. Their calculated Nitrogen Index (NI) was then compared with ANCN. Patient characteristics: median age: 48.5 (range: 26-78). C/T indication: adjuvant-18 (lymph node +ve 10, -ve 8), metastatic-6, neoadjuvant-1, local recurrence-1. The protocol was completed by 13 patients and continues for 3, while 10 patients had fewer than 5 measurements due to death, refusal or inconvenience. The confounding clinical events included 2 deaths due to progressive disease, 3 major infections in 2 patients and in 1 case G-CSF was started by the clinician.There was no significant change in TBN, NI or % body fat during treatment. Following C/T: when NI<0.89, 9 of 11 (81%) courses led to ANCN<1.0, and for NI>0.89, 21 of 82 (26%) courses led to ANCN<1.0 (Fisher Exact Test: p<0.001). The 2 deaths, but none of the infections, occurred in patients with NI<0.89. Further stratification of NI>0.89 showed no significant predictive ability for ANCN. We conclude that low NI is predictive of neutropoenia, although few from this subset of patients would benefit from its measurement. It may be better utilised in patients with suspected nutritional deficiencies.