Prolonged clinical benefit with metronomic chemotherapy in patients with metastatic breast cancer.
The clinical efficacy and antiangiogenic effect of low-dose, metronomic administration of cyclophosphamide (CTX) and methotrexate (MTX) (CM) have been demonstrated. The authors report results and long-term follow-up for patients with metastatic breast carcinoma who obtained prolonged clinical benefit with CM. Prospectively collected data from two successive clinical trials were evaluated. From July 1997 to October 2003, patients with metastatic breast carcinoma were treated with low-dose oral chemotherapy (MTX 2.5 mg, twice daily on day 1 and day 2 or 4, and CTX 50 mg daily). Patients who achieved prolonged clinical benefit for a duration of 12 months or more (complete remission, partial remission or stabilization of disease) were considered for the analysis. Median follow-up was 23 months. A total of 153 patients were enrolled and are evaluable: Eastern Cooperative Oncology Group performance status 0-1 in 90 patients, two or more sites of metastatic disease in 97 patients, zero regimen for metastatic breast carcinoma in 48 patients. Among 153 patients, five demonstrated complete remission and 25 partial remission. The proportion of patients who achieved prolonged clinical benefit was 15.7% (95% confidence interval 9.9-21.4%). Median time to progression for patients with prolonged clinical benefit was 21 months (range 12-37+ months). One patient maintained complete remission 42 months after therapy discontinuation. At the multivariate analysis endocrine responsiveness and the achievement of an objective response significantly correlated with the achievement of prolonged clinical benefit. Metronomic chemotherapy can induce prolonged clinical benefit in metastatic breast cancer, supporting its role as an additional therapeutic tool in the treatment of patients with metastatic breast carcinoma.
Orlando
Laura
L
Unit of Research in Medical Senology, European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy. laura.orlando@ieo.it
Cardillo
Anna
A
Rocca
Andrea
A
Balduzzi
Alessandra
A
Ghisini
Raffaella
R
Peruzzotti
Giulia
G
Goldhirsch
Aron
A
D'Alessandro
Claudia
C
Cinieri
Saverio
S
Preda
Lorenzo
L
Colleoni
Marco
M
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003520:Cyclophosphamide / Q000008:administration & dosage* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008727:Methotrexate / Q000008:administration & dosage* / Q000627:therapeutic use; D008875:Middle Aged; D009362:Neoplasm Metastasis; D042461:Vascular Endothelial Growth Factor A / Q000097:blood / Q000378:metabolism
C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D003520:Cyclophosphamide; D008727:Methotrexate