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 (Po0.0001), with a significantly lower drop in EC-GT patients (P ¼ 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 LVEFo50%. Transient transaminitis occurred in both treatment arms with significantly more in EC-GT patients postchemotherapy (AST P ¼ 0.03, ALT P ¼ 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.

The Efficacy and Safety of Gemcitabine Plus Paclitaxel Compared to Doxorubicin Plus Cyclophosphamide as Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer

“…The reason of this reduction may be attributed to advances in chemotherapy. Currently, anthracyclin-and taxanebased combination chemotherapy is considered as standard regimen in patients with locally advanced breast cancer [11]. Despite improvement in adjuvant therapies, when metastasis occurs, the patient is not considered curable [12,1].…”

Update Mammakarzinom 2019 Teil 1 – Implementierung der Ergebnisse neuer Studienkonzepte beim frühen Mammakarzinom in die klinische Praxis

“…In einigen Studien ist die Wirksamkeit von Gemcitabin, nab-Paclitaxel und Carboplatin beim frühen Mammakarzinom bereits untersucht worden [70][71][72][73][74][75][76][77][78][79][80]. Zusammengefasst zeigten diese Studien, dass eine Hinzunahme von Gemcitabin zu einer Standardtherapie zu keiner Verbesserung führte und in einem Vergleich zwischen einer Standardtherapie und einer platinhaltigen Therapie Letztere einen Vorteil erbrachte.…”

Addition of gemcitabine to paclitaxel, epirubicin, and cyclophosphamide adjuvant chemotherapy for women with early-stage breast cancer (tAnGo): final 10-year follow-up of an open-label, randomised, phase 3 trial

“…Cardiac, pulmonary and hepatic function were initially monitored at four time points (randomisation, mid-chemotherapy, post-chemotherapy and 6-months post-chemotherapy) and showed the treatment regimens as equally well tolerated, only causing mild to moderate reduction in pulmonary function, which recovered completely by 6 months, and gemcitabine causing increased levels of liver transaminases but no adverse clinical events 10 . For the evaluation of long-term toxicity, these assessments were also undertaken at 5 and 10 years post-treatment.…”

“…A preliminary safety analysis without outcome data on the first 135 patients reported in 2008, demonstrated that both regimens were well tolerated, with only temporary changes in pulmonary function and transaminitis 10 . The preliminary results of tAnGo were presented as a conference abstract in 2008 at a median of 3 years follow-up 11 , and showed no benefit from the addition of gemcitabine (DFS HR=1·0 (95%CI 0·8-1·2), p=0·96, OS HR=1·1 (95%CI 0·9-1·4), p=0·35).…”