Purpose : Lonidamine (LND) can enhance the activity of anthracyclines in patients with metastatic breast cancer. A multicenter, prospective, randomized trial was designed to determine whether the association of LND with high-dose epirubicin plus cyclophosphamide (EC) could improve disease-free survival (DFS) in patients with early breast cancer (BC) compared with EC alone. Granulocyte colony-stimulating factor (G-CSF) was added to maintain the EC dose-intensity. Patients and Methods: From October 1991 to April 1994, 506 patients with stage I/II BC Were randomly assigned to four groups: (A) epirubicin 120 mg/m(2) and cyclophosphamide 600 mg/m(2) administered intravenously on day 1 every 21 days for four cycles (124 patients); (B) EC plus LND 450 mg/d administered orally (125 patients); (C) EC plus G-CSF administered subcutaneously (129 patients); (D) EC plus LND plus G-CSF (128 patients). Results: Median follow-up was 55 months. Five-year DFS rate was similar for LND (B+D groups; 69.6%) versus non-LND arms (A+C groups; 70.3%) and G-CSF (C+D groups; 67.2%) versus non-G-CSF arms (A+B groups; 72.9%). Five-year overall survival (OS) was comparable in LND (79.1%) versus nonAND arms (81.3%) and in G-CSF (80.6%) versus non-G-CSF arms (79.6%). DFS and OS distributions in LND and G-CSF arms did not change according to tumor size, node, receptor, and menopausal status. G-CSF dramatically reduced hematologic toxicity without having a significant impact on dose-intensity (98.1% v 95.5% for C+D and A+B groups, respectively). Conclusion: EC is active and well tolerated in patients with. early breast cancer. The addition of LND or G-CSF does not improve DFS or OS. (C) 2003 by American Society of Clinical Oncology.
Addition of either lonidamine or granulocyte colony-stimulating factor does not improve survival in early breast cancer patients treated with high-dose epirubicin and cyclophosphamide / P., Papaldo; M., Lopez; Cortesi, Enrico; E., Cammilluzzi; M., Antimi; E., Terzoli; G., Lepidini; P., Vici; C., Barone; G., Ferretti; S., Di Cosimo; C., Nistico; P., Carlini; F., Conti; L., Di Lauro; C., Botti; C., Vitucci; A., Fabi; D., Giannarelli; P., Marolla; M., Di Maio; F., Perrone; C., Gallo; R. V., Iaffaioli; L., Manzione; F. V., Piantedosi; S., Cigolari; A., Illiano; S., Barbera; S. F., Robbiati; E., Piazza; G. P., Ianniello; L., Frontini; E., Veltri; F., Castiglione; F., Rosetti; E., De Maio; P., Maione; C., Gridelli; A., Rossi; E., Barletta; M. L., Barzelloni; G., Signoriello; D., Bilancia; A., Dinota; G., Rosati; D., Germano; A., Lamberti; V., Pontillo; L., Brancacio; C., Crispino; M., Esposito; C., Battiloro; G., Tufano; A., Cioffi; V., Guardasole; V., Angelini; G., Guidetti; S., Barbera; F., Renda; F., Romano; A., Volpintesta; S. F., Robbiati; M., Sannicolo; V., Filipazzi; G., Esani; A., Gambaro; S., Ferrario; V., Tinessa; M. G., Caprio; S., Zonato; M., Cabiddu; A., Raina; E., Veltri; M., D'Aprile; G., Pistillucci; G., Porcile; O., Ostellino; O., Vinante; G., Azzarello; V., Gebbia; N., Borsellino; A., Testa; G., Gasparini; A., Morabito; D., Gattuso; S., Romito; F., Carrozza; S., Fava; A., Calcagno; E., Grimi; O., Bertetto; L., Ciuffreda; G., Parello; L., Maiorino; A., Santoro; M., Santoro; G., Failla; R. A., Aiello; A., Bearz; R., Sorio; S., Scalone; M., Clerici; R., Bollina; P., Belloni; C., Sacco; A., Sibau; V., Adamo; G., Altavilla; A., Scimone; M., Spatafora; V., Bellia; M. R., Hopps; S., Monfardini; A., Favaretto; M., Stefani; G. M., Corradini; G., Pavia; G., Scagliotti; S., Novello; G., Selvaggi; M., Tonato; S., Darwish; G., Michetti; M. O., Belometti; R., Labianca; A., Quadri; F., De Marinis; M. R., Migliorino; O., Martelli; G., Colucci; D., Galetta; F., Giotta; L., Isa; P., Candido; N., Rossi; A., Calandriello; F., Ferrau; E., Malaponte; S., Barni; M., Cazzaniga; N., Gebbia; Valerio, Mr; M., Belli; G., Colantuoni; M. A., Capuano; M., Angiolillo; F., Sollitto; A., Ardizzoia; G., Luporini; M. C., Locatelli; F., Pari; E., Aitini; T., Pedicini; A., Febbraro; C., Zollo; F., Di Costanzo; R., Bartolucci; S., Gasperoni; F., Gaion; G., Palazzolo; E., Galligioni; O., Caffo; E., Cortesi; G., D'Auria; C., Curcio; M., Vasta; C., Bumma; A., Celano; S., Bretti; G., Nettis; A., Anselmo; R., Mattioli; C., Nistico; A., Aschelter; P., Foa. - In: JOURNAL OF CLINICAL ONCOLOGY. - ISSN 0732-183X. - 21:18(2003), pp. 3462-3468. [10.1200/jco.2003.03.034]
Addition of either lonidamine or granulocyte colony-stimulating factor does not improve survival in early breast cancer patients treated with high-dose epirubicin and cyclophosphamide
CORTESI, Enrico;
2003
Abstract
Purpose : Lonidamine (LND) can enhance the activity of anthracyclines in patients with metastatic breast cancer. A multicenter, prospective, randomized trial was designed to determine whether the association of LND with high-dose epirubicin plus cyclophosphamide (EC) could improve disease-free survival (DFS) in patients with early breast cancer (BC) compared with EC alone. Granulocyte colony-stimulating factor (G-CSF) was added to maintain the EC dose-intensity. Patients and Methods: From October 1991 to April 1994, 506 patients with stage I/II BC Were randomly assigned to four groups: (A) epirubicin 120 mg/m(2) and cyclophosphamide 600 mg/m(2) administered intravenously on day 1 every 21 days for four cycles (124 patients); (B) EC plus LND 450 mg/d administered orally (125 patients); (C) EC plus G-CSF administered subcutaneously (129 patients); (D) EC plus LND plus G-CSF (128 patients). Results: Median follow-up was 55 months. Five-year DFS rate was similar for LND (B+D groups; 69.6%) versus non-LND arms (A+C groups; 70.3%) and G-CSF (C+D groups; 67.2%) versus non-G-CSF arms (A+B groups; 72.9%). Five-year overall survival (OS) was comparable in LND (79.1%) versus nonAND arms (81.3%) and in G-CSF (80.6%) versus non-G-CSF arms (79.6%). DFS and OS distributions in LND and G-CSF arms did not change according to tumor size, node, receptor, and menopausal status. G-CSF dramatically reduced hematologic toxicity without having a significant impact on dose-intensity (98.1% v 95.5% for C+D and A+B groups, respectively). Conclusion: EC is active and well tolerated in patients with. early breast cancer. The addition of LND or G-CSF does not improve DFS or OS. (C) 2003 by American Society of Clinical Oncology.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
