Fluorouracil, Doxorubicin, and Cyclophosphamide (FAC) Versus FAC Followed by Weekly Paclitaxel As Adjuvant Therapy for High-Risk, Node-Negative Breast Cancer: Results From the GEICAM/2003-02 Study

• Published in: Journal of clinical oncology Vol. 31; no. 20; pp. 2593 - 2599
• Main Authors: MARTIN, Miguel, RUIZ, Amparo, MUNOZ-MATEU, Montserrat, DORCA RIBUGENT, Joan, LOPEZ-VEGA, José Manuel, JARA, Carlos, ESPINOSA, Enrique, MENDIOLA FERNANDEZ, César, ANDRES, Raquel, RIBELLES, Nuria, PLAZAOLA, Arrate, SANCHEZ-ROVIRA, Pedro, RUIZ BORREGO, Manuel, SALVADOR BOFILL, Javier, CRESPO, Carmen, CARABANTES, Francisco J, SERVITJA, Sonia, IGNACIO CHACON, José, RODRIGUEZ, César A, HERNANDO, Blanca, ALVAREZ, Isabel, CARRASCO, Eva, LLUCH, Ana, BARNADAS, Agustí, GONZALEZ, Sonia, CALVO, Lourdes, MARGELI VILA, Mireia, ANTON, Antonio, RODRIGUEZ-LESCURE, Alvaro, SEGUI-PALMER, Miguel Angel
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Society of Clinical Oncology 10.07.2013
• Subjects: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Biological and medical sciences; Breast Neoplasms - drug therapy; Breast Neoplasms - mortality; Breast Neoplasms - pathology; Breast Neoplasms - surgery; Chemotherapy, Adjuvant; Confidence Intervals; Cyclophosphamide - administration & dosage; Cyclophosphamide - adverse effects; Disease-Free Survival; Dose-Response Relationship, Drug; Doxorubicin - administration & dosage; Doxorubicin - adverse effects; Drug Administration Schedule; Female; Fluorouracil - administration & dosage; Fluorouracil - adverse effects; Follow-Up Studies; Gynecology. Andrology. Obstetrics; Humans; Kaplan-Meier Estimate; Lymph Nodes - pathology; Mammary gland diseases; Mastectomy - methods; Maximum Tolerated Dose; Medical sciences; Middle Aged; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Neoplasm Invasiveness - pathology; Neoplasm Recurrence, Local - mortality; Neoplasm Recurrence, Local - pathology; Neoplasm Recurrence, Local - therapy; Neoplasm Staging; Paclitaxel - administration & dosage; Paclitaxel - adverse effects; Proportional Hazards Models; Risk Assessment; Survival Analysis; Treatment Outcome; Tumors; Antineoplastic agent; High risk; Breast disease; Adjuvant treatment; Administration schedule; Early stage; Doxorubicin; Negative result; Isomerases; Cancerology; Taxane derivatives; Paclitaxel; Antimitotic; Fluorouracil; DNA topoisomerase (ATP-hydrolysing); Enzyme; Fluoropyrimidine derivatives; Transferases; Enzyme inhibitor; Breast cancer; Topoisomerase II inhibitor; Malignant tumor; Thymidylate synthase; Mammary gland diseases; Cytometry; Alkylating agent; Oxazaphosphinane derivatives; Antibiotic; Cyclophosphamide; Antimetabolic; Methyltransferases; Nitrogen mustard; Pyrimidine derivatives; Anthracyclins; Comparative study; Cancer
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2012.46.9841

Adding taxanes to anthracycline-based adjuvant therapy improves survival outcomes of patients with node-positive breast cancer (BC). Currently, however, most patients with BC are node negative at diagnosis. The only pure node-negative study (Spanish Breast Cancer Research Group 9805) reported so far showed a docetaxel benefit but significant toxicity. Here we tested the efficacy and safety of weekly paclitaxel (wP) in node-negative patients, which is yet to be established. Patients with BC having T1-T3/N0 tumors and at least one high-risk factor for recurrence (according to St. Gallen 1998 criteria) were eligible. After primary surgery, 1,925 patients were randomly assigned to receive fluorouracil, doxorubicin, and cyclophosphamide (FAC) × 6 or FAC × 4 followed by wP × 8 (FAC-wP). The primary end point was disease-free survival (DFS) after a median follow-up of 5 years. Secondary end points included toxicity and overall survival. After a median follow-up of 63.3 months, 93% and 90.3% of patients receiving FAC-wP or FAC regimens, respectively, remained disease free (hazard ratio [HR], 0.73; 95% CI, 0.54 to 0.99; log-rank P = .04). Thirty-one patients receiving FAC-wP versus 40 patients receiving FAC died (one and seven from cardiovascular diseases, respectively; HR, 0.79; 95% CI, 0.49 to 1.26; log-rank P = .31). The most relevant grade 3 and 4 adverse events in the FAC-wP versus the FAC arm were febrile neutropenia (2.7% v 3.6%), fatigue (7.9% v 3.4%), and sensory neuropathy (5.5% v 0%). For patients with high-risk node-negative BC, the adjuvant FAC-wP regimen was associated with a small but significant improvement in DFS compared with FAC therapy, in addition to manageable toxicity, especially regarding long-term cardiac effects.