title: Safety and therapeutic effect of metronomic chemotherapy with cyclophosphamide and celecoxib in advanced breast cancer patients.
abstract: Metronomic chemotherapy (MCT), the chronic administration, at regular intervals, of low doses of chemotherapeutic drugs without extended rest periods, allows chronic treatment with therapeutic efficacy and low toxicity. Our preclinical results suggested that combined MCT with cyclophosphamide and celecoxib could inhibit breast cancer growth. The aim of this study was to determine the toxicity, safety and efficacy of oral MCT with cyclophosphamide 50 mg per orem daily and celecoxib 400 mg (200 mg per orem two-times a day) in advanced breast cancer patients. During the first stage of the study, the therapeutic response consisted of prolonged stable disease for ≥24 weeks in six out of 15 (40%) patients with a median duration of 37.5 weeks and a partial response in one out of 15 (response rate: 6.7%) patients lasting 6 weeks. The overall clinical benefit rate was 46.7%. The median time to progression was 14 weeks. Progression-free survival at 24 weeks was 40% and the 1-year overall survival rate was 46.7%. The adverse events were mild (gastric, grade 1; and hematologic, grade 1 or 2). No grade 3 or 4 toxicities were associated with the treatment. Evaluation of patients' quality of life showed no changes during the response period. MCT with cyclophosphamide plus celecoxib is safe and shows a therapeutic effect in advanced breast cancer patients.
authors.affiliation: Institute of Experimental Genetics, School of Medical Sciences, National University of Rosario, Argentina.
authors.forename: Herman A
authors.initials: HA
authors.lastname: Perroud
authors.forename: Maria José
authors.initials: MJ
authors.lastname: Rico
authors.forename: Carlos M
authors.initials: CM
authors.lastname: Alasino
authors.forename: Francisco
authors.initials: F
authors.lastname: Queralt
authors.forename: Leandro E
authors.initials: LE
authors.lastname: Mainetti
authors.forename: Stella M
authors.initials: SM
authors.lastname: Pezzotto
authors.forename: Viviana R
authors.initials: VR
authors.lastname: Rozados
authors.forename: O Graciela
authors.initials: OG
authors.lastname: Scharovsky
mesh_terms: D059250:Administration, Metronomic; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000068579:Celecoxib; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009360:Neoplastic Cells, Circulating / Q000187:drug effects; D011720:Pyrazoles / Q000008:administration & dosage; D011788:Quality of Life; D013449:Sulfonamides / Q000008:administration & dosage; D011795:Surveys and Questionnaires; D016896:Treatment Outcome
chemical_list: D011720:Pyrazoles; D013449:Sulfonamides; D003520:Cyclophosphamide; D000068579:Celecoxib