title: tAnGo: a randomised phase III trial of gemcitabine in paclitaxel-containing, epirubicin/cyclophosphamide-based, adjuvant chemotherapy for early breast cancer: a prospective pulmonary, cardiac and hepatic function evaluation.
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 FEV(1) 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.
authors.affiliation: CR UK Department of Medical Oncology, Christie Hospital, Manchester M20 4BX, UK. Andrew.Wardley@christie.nhs.uk
authors.forename: A M
authors.initials: AM
authors.lastname: Wardley
authors.forename: L
authors.initials: L
authors.lastname: Hiller
authors.forename: H C
authors.initials: HC
authors.lastname: Howard
authors.forename: J A
authors.initials: JA
authors.lastname: Dunn
authors.forename: A
authors.initials: A
authors.lastname: Bowman
authors.forename: R E
authors.initials: RE
authors.lastname: Coleman
authors.forename: I N
authors.initials: IN
authors.lastname: Fernando
authors.forename: D M
authors.initials: DM
authors.lastname: Ritchie
authors.forename: H M
authors.initials: HM
authors.lastname: Earl
authors.forename: C J
authors.initials: CJ
authors.lastname: Poole
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000556:secondary; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy / Q000556:secondary; D018275:Carcinoma, Lobular / Q000188:drug therapy / Q000556:secondary; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D006321:Heart / Q000187:drug effects*; D006334:Heart Function Tests; D006801:Humans; D008099:Liver / Q000187:drug effects*; D008111:Liver Function Tests; D008168:Lung / Q000187:drug effects*; D017239:Paclitaxel / Q000008:administration & dosage; D011446:Prospective Studies; D012129:Respiratory Function Tests; D015996:Survival Rate; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D015251:Epirubicin; D003520:Cyclophosphamide; D017239:Paclitaxel; D000093542:Gemcitabine