Lani
08-01-2007, 08:39 AM
metronomic chemotherapy is the frequent dosing of very small doses of chemotherapy (far far less than given when trying to kill tumors), sometimes giving it daily without interruption. It works not by killing cancer cells directly but by killing the lining cells of the new blood vessels tumors try to recruit to supply them with nutrients.
It has been utilized in Italy and Canada in trials and seems as if it would be especially useful in the elderly who probably couldn't tolerate conventional chemotherapy.
The way proposed to determine whether or not it is likely to work in metastatic bc patients is by testing serum EGFR (also known as her1) and serum her2.
31 July 2007
EGFR and HER2-neu predict response to metronomic chemotherapy
MedWire News: Serum levels of the human epidermal growth factor receptors 1 (EGFR) and 2 (Her2-neu) have been shown to predict response to metronomic chemotherapy in women with metastatic breast cancer.
Research published in the journal Cancer shows that low serum levels of EGFR before the start of chemotherapy and elevated HER2-neu levels 2 months post-treatment are associated with a reduced response rate and worse prognosis in terms of progression-free survival (PFS) and overall survival (OS).
Italian researchers from the European Institute of Oncology in Milan prospectively evaluated the prognostic and predictive role of serum EGFR and serum HER2-neu in a phase III trial of advanced breast cancer patients treated with low-dose "metronomic" chemotherapy.
In the trial, 178 women were randomized to receive oral cyclophosphamide (50 mg, once daily) and methotrexate (2.5 mg, twice daily) on days 1 and 4 every week with or without oral thalidomide (200 mg, once daily). No differences in PFS or OS were noted among the two treatment arms, so the patients were treated as a single cohort.
Serum levels of EGFR and HER2-neu were assessed before and after 2 months' treatment. Although elevated (>15 ng/ml) HER2-neu at baseline was not associated with response rates, values at 2 months were. HER2-neu levels at 2 months were significantly higher than at baseline in women who had progressive disease (20.7 vs 41.3 ng/ml, p=0.045), and were significantly associated with worse prognosis.
"Upon multivariate analysis an increase of serum HER2-neu =20% after 2 months of therapy resulted in an independent prognostic factors for PFS," Maria Teresa Sandri and colleagues report.
Indeed, they found that women with an increase in serum HER2-neu of 20% or more and with levels higher than 15 ng/ml at 2 months had a PFS of 2.9 months, whereas those with elevations under this cut-off point had a PFS of 14.9 months.
Serum EGFR levels did not change significantly from baseline to the 2 month assessment, and did not alter much over the course of chemotherapy. However, low EGFR levels (<45 ng/ml) at baseline were predictive of lower response rates at 2 months and at 24 weeks (p=0.22). "Moreover they were significantly associated with reduced PFS and OS," says the team.
Sandri et al conclude: "The results of this study indicate that serum HER2-neu and serum EGFR are useful for predicting the response to the treatment and the long-term clinical outcome in metastatic breast cancer patients treated with metronomic chemotherapy."
They add: "The values of these markers should be further explored in prospective and possibly multicenter trials involving new agents with anti-angiogenic activity such as bevacizumab, administered either alone or on combination with chemotherapy."
Cancer 2007; 110: 509-517
http://www3.interscience.wiley.com/cgi-bin/abstract/114278080/ABSTRACT
It has been utilized in Italy and Canada in trials and seems as if it would be especially useful in the elderly who probably couldn't tolerate conventional chemotherapy.
The way proposed to determine whether or not it is likely to work in metastatic bc patients is by testing serum EGFR (also known as her1) and serum her2.
31 July 2007
EGFR and HER2-neu predict response to metronomic chemotherapy
MedWire News: Serum levels of the human epidermal growth factor receptors 1 (EGFR) and 2 (Her2-neu) have been shown to predict response to metronomic chemotherapy in women with metastatic breast cancer.
Research published in the journal Cancer shows that low serum levels of EGFR before the start of chemotherapy and elevated HER2-neu levels 2 months post-treatment are associated with a reduced response rate and worse prognosis in terms of progression-free survival (PFS) and overall survival (OS).
Italian researchers from the European Institute of Oncology in Milan prospectively evaluated the prognostic and predictive role of serum EGFR and serum HER2-neu in a phase III trial of advanced breast cancer patients treated with low-dose "metronomic" chemotherapy.
In the trial, 178 women were randomized to receive oral cyclophosphamide (50 mg, once daily) and methotrexate (2.5 mg, twice daily) on days 1 and 4 every week with or without oral thalidomide (200 mg, once daily). No differences in PFS or OS were noted among the two treatment arms, so the patients were treated as a single cohort.
Serum levels of EGFR and HER2-neu were assessed before and after 2 months' treatment. Although elevated (>15 ng/ml) HER2-neu at baseline was not associated with response rates, values at 2 months were. HER2-neu levels at 2 months were significantly higher than at baseline in women who had progressive disease (20.7 vs 41.3 ng/ml, p=0.045), and were significantly associated with worse prognosis.
"Upon multivariate analysis an increase of serum HER2-neu =20% after 2 months of therapy resulted in an independent prognostic factors for PFS," Maria Teresa Sandri and colleagues report.
Indeed, they found that women with an increase in serum HER2-neu of 20% or more and with levels higher than 15 ng/ml at 2 months had a PFS of 2.9 months, whereas those with elevations under this cut-off point had a PFS of 14.9 months.
Serum EGFR levels did not change significantly from baseline to the 2 month assessment, and did not alter much over the course of chemotherapy. However, low EGFR levels (<45 ng/ml) at baseline were predictive of lower response rates at 2 months and at 24 weeks (p=0.22). "Moreover they were significantly associated with reduced PFS and OS," says the team.
Sandri et al conclude: "The results of this study indicate that serum HER2-neu and serum EGFR are useful for predicting the response to the treatment and the long-term clinical outcome in metastatic breast cancer patients treated with metronomic chemotherapy."
They add: "The values of these markers should be further explored in prospective and possibly multicenter trials involving new agents with anti-angiogenic activity such as bevacizumab, administered either alone or on combination with chemotherapy."
Cancer 2007; 110: 509-517
http://www3.interscience.wiley.com/cgi-bin/abstract/114278080/ABSTRACT