title: Sixteen years follow-up results of a randomized phase II trial of neoadjuvant fluorouracil, doxorubicin, and cyclophosphamide (FAC) compared with cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) in stage III breast cancer: GOCS experience.
abstract: Neoadjuvant chemotherapy (NAC) allows direct evaluation of the tumor's sensitivity to therapy, eradication of micrometastatic disease and the possibility of performing breast conserving surgery. The aim of this study was to describe long-term results of NAC in stage III breast cancer patients. We evaluated 126 patients that participated in a phase II randomized trial of neoadjuvant FAC compared with CMF. Chemotherapy was administered for three cycles prior to definitive surgery and radiotherapy, and then for six cycles as adjuvant. Median follow-up was 4.5 years (range 0.2-16.4). Objective response rate (OR) was similar in both groups (61 % for FAC, 66 % for CMF, P = NS). There were no differences in median disease free survival (DFS) or overall survival (OS) (5.1 vs 3.3 years and 6.7 vs 6.3 years for FAC and CMF, respectively). After 16 years of follow-up, 53 patients are still alive. Multivariate analysis showed that the number of pathologically involved lymph nodes (pLN) was the only factor associated with both, DFS and OS (P = 0.0003 and P = 0.0005, respectively). Both regimens were well tolerated, CMF had higher incidence of grade 3-4 leukopenia, thrombocytopenia, and stomatitis, whereas alopecia was more common in FAC. To the best of our knowledge, this is the first study to report long-term outcomes of FAC and CMF in the neoadjuvant setting. Within the sensitivity of our study, both regimens showed similar OR, long-term toxicity, DFS, and OS rate at 16 years. After 5 years, the hazard of death seems to decline. The prolonged follow-up of this study provides a unique opportunity to evaluate factors that predict long-term outcomes. After 16 years of follow-up, the number of pLN remains the most powerful predictor of survival.
authors: Division of Hematology and Oncology, University of Pittsburgh Cancer Institute, UPMC Cancer Pavilion Room 463, 5150 Centre Ave, Pittsburgh, PA, 15232, USA, leonejp@upmc.edu.
authors: José Pablo
authors: JP
authors: Leone
authors: Julieta
authors: J
authors: Leone
authors: Carlos Teodoro
authors: CT
authors: Vallejo
authors: Juan Eduardo
authors: JE
authors: Pérez
authors: Alberto Omar
authors: AO
authors: Romero
authors: Mario Raul
authors: MR
authors: Machiavelli
authors: Luis
authors: L
authors: Romero Acuña
authors: María Ester
authors: ME
authors: Domínguez
authors: Mario
authors: M
authors: Langui
authors: Hebe Margot
authors: HM
authors: Fasce
authors: Bernardo Amadeo
authors: BA
authors: Leone
authors: Eduardo
authors: E
authors: Ortiz
authors: Julián
authors: J
authors: Iturbe
authors: Ariel Osvaldo
authors: AO
authors: Zwenger
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy / Q000601:surgery; D003520:Cyclophosphamide / Q000009:adverse effects / Q000627:therapeutic use; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000627:therapeutic use; D005500:Follow-Up Studies; D006801:Humans; D008207:Lymphatic Metastasis / Q000473:pathology; D015412:Mastectomy, Segmental; D008727:Methotrexate / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods*; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D011446:Prospective Studies; D013534:Survival; D055815:Young Adult
chemical_list: D004317:Doxorubicin; D003520:Cyclophosphamide; D005472:Fluorouracil; D008727:Methotrexate