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Low-dose
oral methotrexate and cyclophosphamide in metastatic breast cancer: antitumor
activity and correlation with vascular endothelial growth factor levels
Colleoni M, Rocca A, Sandri MT, Zorzino L, Masci G, Nole
F, Peruzzotti G, Robertson C, Orlando L, Cinieri S, de BF, Viale G, Goldhirsch A
Division
of Medical Oncology, European Institute of Oncology, Milan, Italy. marco.colleoni@ieo.it
Background.
Anticancer chemotherapy is thought to be effective by means of direct
cytotoxicity on tumor cells. Alternative mechanisms of efficacy have been
ascribed to several common anticancer agents, including cyclophosphamide (CTX),
methotrexate (MTX), anthracyclines and taxanes, postulating an antiangiogenic
activity.
Patients
and Methods. We evaluated the clinical efficacy and impact on serum vascular
endothelial growth factor (VEGF) levels of low-dose oral MTX and CTX in patients
with metastatic breast cancer.
MTX was administered 2.5 mg bd on days 1 and 2 each week and CTX 50 mg/day
administered continuously.
Results.
Sixty-four patients were enrolled, 63 were evaluable: Eastern Cooperative
Oncology Group (ECOG) performance status 0-1, > or =2 sites of metastatic
disease (n = 50 patients), progressive disease at study entry (n = 51), 1
regimen for metastatic disease (n = 32) and > or =2 regimens (n = 20).
Among the 63 evaluable patients, there were two complete remissions (CR), 10
partial remissions (PR) for an overall response rate of 19.0% (95% CI 10.2% to
30.9%) and an overall clinical benefit (CR+ PR+ stable disease >24 weeks) of
31.7% (95% CI 20.6% to 44.7%).
Grade > or =2 leucopenia was registered in only 13 patients.
The median serum VEGF level for the subgroup of patients on treatment for at
least 2 months decreased with treatment from 315 pg/ml (95% CI 245 to 435) at
baseline to 248 pg/ml (95% CI 205 to 311) at 2 months (P <0.001).
Both responders and non-responders showed similar reductions in serum VEGF (P =
0.78).
After 6 months patients still on treatment had a median VEGF level of 195 pg/ml
(95% CI 96 to 355), which was significantly lower than the median baseline
values (P = 0.001).
Conclusions.
Continuously low-dose CTX and MTX is minimally toxic and effective in heavily
pretreated breast cancer patients.
A drop in VEGF was associated with the treatment and so alternative hypotheses,
other than that of direct toxicity on tumor cells, must be favored when trying
to explain the anticancer effect.
PMID:
11863115 [PubMed - indexed for MEDLINE]
Source:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11863115&dopt=Abstract |
