A prospective evaluation of pulmonary, cardiac, and hepatic function (fn) in ‘tAnGo’: A randomized phase III trial of gemcitabine (G) in paclitaxel (T)-containing, epirubicin/cyclophosphamide (EC)-based, adjuvant chemotherapy (CT) for early stage breast cancer

Abstract

821 Background: tAnGo is an ongoing 3000-patient (pt) randomized trial evaluating for the first time the role of G in adjuvant CT for breast cancer. We present the results of a preliminary prospective safety study designed to assess the incidence of any treatment (trt)-related clinical or sub-clinical disturbances of pulmonary, cardiac, or hepatic fn in the first 135 pts randomised. Methods: Pulmonary (Hb-adjusted TLCO, FEV1, FVC, CXR), cardiac (LVEF, ECG), and hepatic (AST/ALT) fn tests were conducted in 135 pts (66 EC+T, 69 EC+GT) at baseline, mid-CT, post-CT/pre-RT, and 6 months post-CT. Results: Pulmonary fn tests: majority normal at all time points, with no differences between trts or changes over time in FEV1 (p>0.3 and 0.9 resp) or FVC (p=0.95 and 0.5 resp). TLCO dropped marginally during trt (p<0.001), slightly lower for EC+GT pts (p=0.03). 94% of all CXRs normal with no differences between trts (p>0.25) and no changes over time (p=0.14). Cardiac fn tests: 95% of all Echo/MUGA scans and 90% of all ECGs normal, with no differences between trts (p>0.35 and >0.25 resp) and no changes in Echo/MUGAs over time (p=0.4); only a slight time effect in ECGs (p=0.03). Hepatic fn tests: 92% of all AST levels and 82% of all ALT levels normal (majority of abnormal results graded 1/2): EC+T pts show a modest increase in transaminases at mid-CT but this resolves by post-CT (AST p=0.08 and ALT p=0.38 for change over time); transaminase increases in EC+GT pts persist post-CT but resolve by 6 months (AST p=0.004 and ALT p=0.001 resp for change over time). Acute skin toxicity during RT: 87% of reports graded this as Nil/Mild; only 1% as severe; no difference between trts (p>0.1), although severity increased over time (p<0.0001). There were no trt related deaths. Conclusions: These data suggest that clinically relevant trt effects on pulmonary or cardiac fn will be rare over the course of the entire study. Reported transaminase increases are both modest and reversible. Long term follow-up tests will be performed at 5 and 10 yrs. No significant financial relationships to disclose.