{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T14:39:54Z","timestamp":1790779194781,"version":"4.1.0"},"reference-count":39,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"18","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCO"],"published-print":{"date-parts":[[2003,9,15]]},"abstract":"<jats:p> 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. <\/jats:p><jats:p> 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<jats:sup>2<\/jats:sup> and cyclophosphamide 600 mg\/m<jats:sup>2<\/jats:sup> 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). <\/jats:p><jats:p> 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\u2013G-CSF arms (A+B groups; 72.9%). Five-year overall survival (OS) was comparable in LND (79.1%) versus non-LND arms (81.3%) and in G-CSF (80.6%) versus non\u2013G-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). <\/jats:p><jats:p> 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. <\/jats:p>","DOI":"10.1200\/jco.2003.03.034","type":"journal-article","created":{"date-parts":[[2003,9,12]],"date-time":"2003-09-12T17:44:46Z","timestamp":1063388686000},"page":"3462-3468","source":"Crossref","is-referenced-by-count":66,"title":["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"],"prefix":"10.1200","volume":"21","author":[{"given":"Paola","family":"Papaldo","sequence":"first","affiliation":[{"name":"From the Departments of Medical Oncology and Surgery, Regina Elena Cancer Institute; Division of Medical Oncology, University \u201cLa Sapienza\u201d, School of Medicine; Division of Medical Oncology, S Filippo Neri Hospital; Division of Medical Oncology, S Eugenio Hospital; Division of Medical Oncology, S Camillo Hospital; and Division of Medical Oncology, Catholic University School of Medicine, Rome, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Lopez","sequence":"additional","affiliation":[{"name":"From the Departments of Medical Oncology and Surgery, Regina Elena Cancer Institute; 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