Trastuzumab in combination with metronomic cyclophosphamide and methotrexate in patients with HER-2 positive metastatic bre

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BMC Cancer. 2006 Sep 15;6:225.

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Trastuzumab
in combination with metronomic cyclophosphamide and methotrexate in
patients with HER-2 positive metastatic breast cancer.


 
Orlando L, Cardillo A, Ghisini R, Rocca A, Balduzzi A, Torrisi R, Peruzzotti G, Goldhirsch A, Pietri E, Colleoni M.
Unit
of Research in Medical Senology, Department of Medicine, European
Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy.

 
BACKGROUND: HER2/neu
overexpression is linked to promotion of angiogenesis in breast cancer.
We therefore tested the activity of the combination of Trastuzumab with
metronomic, low dose chemotherapy with cyclophosphamide (CTX) and
methotrexate (MTX) in metastatic breast cancer (MBC).
 
METHODS: Between
April 2002 and June 2005, twenty-two patients with metastatic breast
cancer with the presence of overexpression or amplification of
HER2-/neu, all pre-treated with trastuzumab plus other cytotoxics, were
treated with trastuzumab (6 mg/kg every three weeks) in combination
with metronomic chemotherapy (MTX 2.5 mg, bid on Day 1 and Day 4 every
week) and CTX (50 mg daily) (CM).
 
RESULTS: The 22 enrolled patients are
evaluable: most had an ECOG performance status of 0 (17 pts), and all
were pre-treated with chemotherapy for metastatic disease; 14 had
progressive disease at study entry, and 11 had progressive disease
during the last trastuzumab therapy. Metastatic sites included: lung (5
pts), liver (14 pts), bone (12 pts), lymph nodes (8 pts), central
nervous system (CNS) (9 pts). We observed 4 partial remission (PR)
(18%, 95% CI 5-40%), 10 stable disease (SD) (46%, 95% CI 24-68%), and 8
PD (36%, CI 17-59%). The clinical benefit (RP plus RC plus SD for >
or = 24 weeks) in all pts and in pts with disease resistant to previous
trastuzumab therapy were 46% (95% CI, 24-68%) and 27% (95% CI, 6-61%),
respectively. Median time to progression was 6 months and median
duration of treatment was 5 months (range, 0,7 to 18.4 months and
range, 1 to 18 months, respectively). Overall clinical toxicity was
generally mild. Grade > or =2 reversible liver toxicity and
leukopenia were reported in 5 and 3 pts, respectively.
 
CONCLUSION: The
combination of trastuzumab and metronomic chemotherapy is effective and
minimally toxic in advanced breast cancer patients. The efficacy
observed in patients with disease resistant to trastuzumab supports the
need of larger trial to confirm a role of this combination to delay
acquired trastuzumab resistance.