title: Oral metronomic cyclophosphamide and methotrexate plus fulvestrant in advanced breast cancer patients: a mono-institutional case-cohort report.
abstract: Fulvestrant is effective in postmenopausal women with estrogen receptor-positive advanced breast cancer (ABC). So far, no published data exist on fulvestrant combined with chemotherapy. We retrospectively assessed the role of combining oral metronomic cyclophosphamide and methotrexate (CM) to fulvestrant in two cohorts (A and B) of heavily pre-treated estrogen receptor-positive advanced ABC patients. From October 2006 to September 2009, 33 postmenopausal patients received fulvestrant 250 mg via i.m. injection q28 days. In A, 20 patients added metronomic cyclophosphamide (50 mg p.o. daily) and methotrexate (2.5 mg p.o. twice daily on day 1 and day 4 weekly) after disease progression, continuing fulvestrant at the same dose. In B, 13 patients started fulvestrant plus metronomic CM upfront. Thirty-two patients were evaluable for response. Clinical benefit (partial response + stable disease >24 months) for A + B was 56% (95% CI 38-74%). The addition of metronomic CM did not determine relevant toxicities. Treatment with fulvestrant plus metronomic CM was effective in advanced ABC and was minimally toxic providing long-term disease control in a high proportion of patients. The prolonged clinical benefit, often desirable in such patients, supports this regimen as an additional and useful therapeutic tool.
authors: European Institute of Oncology, Medical Oncology, Milan, Italy. gaetano.aurilio@ieo.it
authors: Gaetano
authors: G
authors: Aurilio
authors: Elisabetta
authors: E
authors: Munzone
authors: Edoardo
authors: E
authors: Botteri
authors: Angela
authors: A
authors: Sciandivasci
authors: Laura
authors: L
authors: Adamoli
authors: Ida
authors: I
authors: Minchella
authors: Angela
authors: A
authors: Esposito
authors: Daniela
authors: D
authors: Cullurà
authors: Giuseppe
authors: G
authors: Curigliano
authors: Marco
authors: M
authors: Colleoni
authors: Aron
authors: A
authors: Goldhirsch
authors: Franco
authors: F
authors: Nolè
mesh_terms: D059250:Administration, Metronomic; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D015331:Cohort Studies; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D004334:Drug Administration Schedule; D004958:Estradiol / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D005260:Female; D000077267:Fulvestrant; D006801:Humans; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D017698:Postmenopause; D011960:Receptors, Estrogen / Q000378:metabolism; D012189:Retrospective Studies
chemical_list: D011960:Receptors, Estrogen; D000077267:Fulvestrant; D004958:Estradiol; D003520:Cyclophosphamide; D008727:Methotrexate