1. ¹CR UK Department of Medical Oncology, Christie Hospital, Manchester M20 4BX, UK
2. ²Warwick Medical School Clinical Trials Unit, University of Warwick, Coventry CV4 7AL, UK
3. ³Cancer Research UK Clinical Trials Unit, University of Birmingham, Birmingham B15 2TT, UK
4. ⁴Edinburgh Cancer Centre, Western General Hospital, Edinburgh EH4 2XU, UK
5. ⁵Cancer Research Centre, Weston Park Hospital, Sheffield S10 2SJ, UK
6. ⁶Cancer Centre, Queen Elizabeth Hospital, Birmingham B15 2TH, UK
7. ⁷Beatson Oncology Centre, Western Infirmary, Glasgow G11 6NT, UK
8. ⁸Oncology Centre, Addenbrookes Hospital, University of Cambridge, Cambridge CB2 0QQ, UK

Correspondence: Dr AM Wardley, Department of Medical Oncology, Cancer Research UK, Christie Hospital, 550 Wilmslow Road, Manchester M20 4BX, UK. E-mail: Andrew.Wardley@christie.nhs.uk

Received 14 February 2008; Revised 23 May 2008; Accepted 2 July 2008; Published online 29 July 2008.

Abstract

tAnGo is a large randomised trial assessing the addition of gemcitabine(G) to paclitaxel(T), following epirubicin(E) and cyclophosphamide(C) in women with invasive higher risk early breast cancer. To assess the safety and tolerability of adding G, a detailed safety substudy was undertaken. A total of 135 patients had cardiac, pulmonary and hepatic function assessed at (i) randomisation, (ii) mid-chemotherapy, (iii) immediately post-chemotherapy and (iv) 6 months post-chemotherapy. Skin toxicity was assessed during radiotherapy. No differences were detected in FEV₁ or FVC levels between treatment arms or time points. Diffusion capacity (TL_CO) reduced during treatment (P<0.0001), with a significantly lower drop in EC-GT patients (P=0.02). Most of the reduction occurred during EC and recovered by 6-months post treatment. There was no difference in cardiac function between treatment arms. Only 11 patients had echocardiography/MUGA results change from normal to abnormal during treatment, with only five having LVEF<50%. Transient transaminitis occurred in both treatment arms with significantly more in EC-GT patients post-chemotherapy (AST P=0.03, ALT P=0.003), although the majority was low grade. There was no correlation between transaminitis and other toxicities. Both treatment regimens reported temporary reductions in pulmonary functions and transient transaminitis levels. Despite these being greater with EC-GT, both regimens appear well tolerated.