P Piedbois1, D Serin2, F Priou3, P Laplaige4, S Greget5, E Angellier6, E Teissier7, J-F Berdah8, M Fabbro9, B Valenza10, P Herait11, V Jehl12, M Buyse12. 1. Hôpital Henri-Mondor, Créteil. Electronic address: pascal.piedbois@hmn.aphp.fr. 2. Institut Sainte-Catherine, Avignon. 3. Hôpital départemental, La Roche-sur-Yon. 4. Clinique Saint-Come et Saint-Damien, Blois. 5. Clinique Sainte-Clotilde, Saint-Louis de la Réunion. 6. Hôpital Fontenoy, Chartres. 7. Clinique Plein Ciel, Mougins. 8. Clinique de l'Espérance, Hyères. 9. CRLCC Val d'Aurelle, Montpellier. 10. Centre Hospitalier, Draguignan, France, for the European Association for Research in Oncology. 11. Soisy-sous-Montmorency. 12. International Drug Development Institute, Brussels, Belgium.
Abstract
BACKGROUND: Adding a taxane to anthracycline-based adjuvant chemotherapy prolongs survival in node-positive patients but optimal dose and schedule remain undetermined. This study aimed to select a dose-dense regimen for further assessment in phase III studies. PATIENTS AND METHODS: Ninety-nine patients with node-positive invasive breast adenocarcinoma were randomly assigned to docetaxel (Taxotere) (T) 75 mg/m2, epirubicin (E) 75 mg/m2 and cyclophosphamide (C) 500 mg/m2 (TEC)x6, every 3 weeks; E 100 mg/m2, C 600 mg/m2 x 4, then T 100 mg/m2 x 4 (EC-->T) or the reverse sequence (T-->EC), every 2 weeks, with pegfilgrastim support. The primary end point was the incidence of grade 4 toxicity. RESULTS:Dose intensity was almost doubled with dose-dense regimens, compared with TEC. Twenty-seven patients experienced grade 4 toxicity: 26%, 40% and 18% with TEC, EC-->T and T-->EC, respectively, mainly neutropenia, but febrile neutropenia occurred only in 11%, 10% and 3%. Grade 3-4 nail disorders, hand-foot syndrome and peripheral neuropathy occurred in 46%, 73% and 68% of patients with TEC, EC-->T and T-->EC, respectively. CONCLUSIONS: Dose-dense regimens yield more frequent and severe nonhematological toxic effects than standard dose TEC regimen. Though grade 4 toxicity rates appear acceptable with the T-->EC regimen, the incidence of grade 3-4 events makes it difficult to recommend either dose-dense regimen for further investigation.
RCT Entities:
BACKGROUND: Adding a taxane to anthracycline-based adjuvant chemotherapy prolongs survival in node-positive patients but optimal dose and schedule remain undetermined. This study aimed to select a dose-dense regimen for further assessment in phase III studies. PATIENTS AND METHODS: Ninety-nine patients with node-positive invasive breast adenocarcinoma were randomly assigned to docetaxel (Taxotere) (T) 75 mg/m2, epirubicin (E) 75 mg/m2 and cyclophosphamide (C) 500 mg/m2 (TEC)x6, every 3 weeks; E 100 mg/m2, C 600 mg/m2 x 4, then T 100 mg/m2 x 4 (EC-->T) or the reverse sequence (T-->EC), every 2 weeks, with pegfilgrastim support. The primary end point was the incidence of grade 4 toxicity. RESULTS: Dose intensity was almost doubled with dose-dense regimens, compared with TEC. Twenty-seven patients experienced grade 4 toxicity: 26%, 40% and 18% with TEC, EC-->T and T-->EC, respectively, mainly neutropenia, but febrile neutropenia occurred only in 11%, 10% and 3%. Grade 3-4 nail disorders, hand-foot syndrome and peripheral neuropathy occurred in 46%, 73% and 68% of patients with TEC, EC-->T and T-->EC, respectively. CONCLUSIONS: Dose-dense regimens yield more frequent and severe nonhematological toxic effects than standard dose TEC regimen. Though grade 4 toxicity rates appear acceptable with the T-->EC regimen, the incidence of grade 3-4 events makes it difficult to recommend either dose-dense regimen for further investigation.
Authors: P Vici; M Brandi; F Giotta; P Foggi; F Schittulli; L Di Lauro; N Gebbia; B Massidda; G Filippelli; D Giannarelli; A Di Benedetto; M Mottolese; G Colucci; M Lopez Journal: Ann Oncol Date: 2011-09-28 Impact factor: 32.976
Authors: Robert I Griffiths; Richard L Barron; Michelle L Gleeson; Mark D Danese; Anthony O'Hagan; Victoria M Chia; Jason C Legg; Gary H Lyman Journal: Pharmacoeconomics Date: 2012-02-01 Impact factor: 4.558
Authors: Patrizia Vici; Laura Pizzuti; Teresa Gamucci; Domenico Sergi; Francesca Conti; Germano Zampa; Pietro Del Medico; Roy De Vita; Marcello Pozzi; Claudio Botti; Simona Di Filippo; Federica Tomao; Isabella Sperduti; Luigi Di Lauro Journal: J Cancer Date: 2014-04-25 Impact factor: 4.207