title: Oral metronomic cyclophosphamide with and without methotrexate as palliative treatment for patients with metastatic breast carcinoma.
abstract: BACKGROUND
  Oral metronomic chemotherapy is a therapeutic option which is particularly attractive due to its ease of administration and low toxic burden. Its mechanism of action probably involves antiangiogenetic effect rather than a classical antiproliferative effect like standard maximally tolerated dose-based regimens.
  
  
  METHODS
  A retrospective analysis of 61 patients with advanced breast carcinoma was carried out with the aim of reporting activity in terms of response rate, control of tumor-related symptoms, outcome, and toxicity. All patients had hormonal therapy-resistant metastatic disease and had previously received two lines of chemotherapy. The first cohort of 22 patients received oral cyclophosphamide at 50 mg/day without interruption until re-evaluation or progressive disease, while the second cohort of 39 patients had oral cyclophosphamide at the above dose plus oral low-dose methotrexate at 2.5 mg orally twice a week.
  
  
  RESULTS
  Overall, a partial response with a median duration of 6 months (range 4-9 months) according to the RECIST criteria was recorded in 18% of patients (95% confidence intervals, CI=8%-28%), and stable disease with a median duration of 5 months (range 3-8 months) was recorded in 35% of cases (95% CI=22%-49%) for a tumor growth control rate of 52%. Symptom control was achieved in 54% of cases. Toxicity was very mild and easily manageable. No cases of extra-hematological grade 3 toxicity were observed. Grade 3 non-febrile neutropenia were recorded in 3% of cases. Liver toxicity was represented by elevation of transaminases in 20 cases (33%), mainly in the cohort of patients receiving cyclophosphamide plus methotrexate.
  
  
  CONCLUSIONS
  Although retrospectively recorded, the data presented in this study support the use of oral metronomic chemotherapy for patients with metastatic breast cancer. Significant clinical activity was seen in heavily pretreated patients without severe grade 3-4 side-effects. Further studies are warranted to optimise the treatment schedule and to select patients who may benefit from such an approach.
authors.affiliation: Medical Oncology Unit La Maddalena Cancer Clinic, via San Lorenzo Colli n. 312d, 90100 Palermo, Italy. vittorio.gebbia@tin.it
authors.forename: Vittorio
authors.initials: V
authors.lastname: Gebbia
authors.forename: Hamouda
authors.initials: H
authors.lastname: Boussen
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Valerio
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015331:Cohort Studies; D003520:Cyclophosphamide / Q000008:administration & dosage* / Q000009:adverse effects; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D009367:Neoplasm Staging; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy / Q000473:pathology; D010166:Palliative Care / Q000379:methods*; D012189:Retrospective Studies
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003520:Cyclophosphamide; D008727:Methotrexate