Adjuvant chemotherapy in older women (ACTION) study – what did we learn from the pilot phase?

Abstract

Background:The ACTION trial was initiated to provide evidence from a randomised trial on the effects of chemotherapy in women aged over 70 years where evidence for risk and benefit are lacking.Methods:This was a randomised, phase III clinical trial for high risk, oestrogen receptor (ER) negative/ER weakly positive early breast cancer. The trial planned to recruit 1000 women aged 70 years and older, randomised to receive 4 cycles of anthracycline chemotherapy or observation. The primary endpoint was relapse-free interval. The trial included a pilot phase to assess the acceptability and feasibility of recruitment.Results:The trial opened at 43 UK centres. Information on number of patients approached was available from 38 centres. Of the 43 eligible patients that were approached, 39 were not randomised due to patients declining entry. After 10 months only 4 patients had been randomised and after discussion with the research funder, the trial was closed and funding terminated.Conclusion:Despite widespread support at several public meetings, input from patient groups including representation on the Trial Management Group, the trial failed to recruit due to the inability to convince patients to accept randomisation. It would therefore seem that randomising the patients to receive chemotherapy vs observation is not a viable design in the current era for this patient population.

Elderly Postmenopausal Patients With Breast Cancer Are at Increased Risk for Distant Recurrence: A Tamoxifen Exemestane Adjuvant Multinational Study Analysis

“…Standard chemotherapy was shown to be superior to oral capecitabine, especially in patients with hormone receptor-negative tumors. Two studies aimed to evaluate the benefit of chemotherapy in elderly patients with breast cancer, in which chemotherapy was compared with a no-treatment arm [25,26]. Both trials failed to recruit and were closed early.…”

Slow accrual of elderly patients with metastatic breast cancer in the Dutch multicentre OMEGA study

“…12 In the ACTION trial, patients were randomised between four cycles of anthracycline/cyclophosphamide or alternatively observation only. 13 In their analysis of potential causes, the ACTION trial investigators stated that in contrast to their pre-trial audits, many patients were not eligible, and eligible ones often refused participation because they did not want to be randomised to the chemotherapy arm. The investigators stated that this is a particularly important issue in trials that use a no-treatment arm.…”

Vers une approche multidisciplinaire optimale du traitement du cancer du sein chez les patientes plus âgées

“…Le premier essai clinique aléatoire effectué chez des patientes de 65 ans et plus atteintes d'un cancer du sein au stade précoce a montré que les patientes traitées par capécitabine présentaient des probabilités de rechute deux fois supérieures (RR : 2,09, 95 %; IC : 1,38-3,17; p < 0,001), et présentaient presque deux fois plus de risques de mourir (RR : 1,85, 95 %; IC : 1,11-3,08; P = 0,02) comparativement à celles traitées par la chimiothérapie standard (cyclophosphamide, méthrotexate et fluoroucacil [CMF] ou cyclophosphamide (Muss et al, 2009). Deux récents essais cliniques aléatoires examinant les divers protocoles de chimiothérapie chez les personnes âgées se sont terminés plus tôt en raison du nombre insuffisant de participantes (Crivellari et al, 2013;Leonard et al, 2011). Des essais en cours (décrits au tableau 1) étudient la chimiothérapie adjuvante chez ce groupe de patientes.…”