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A pilot study of bevacizumab combined with etoposide and cisplatin in breast cancer patients with leptomeningeal carcinomatosis.

Wu PF, Lin CH, Kuo CH, Chen WW, Yeh DC, Liao HW, Huang SM, Cheng AL, Lu YS - BMC Cancer (2015)

Bottom Line: Elevated vascular endothelial growth factor (VEGF) was associated with poor prognosis in leptomeningeal carcinomatosis and anti-angiogenic therapy was found to prolong the survival of mice in preclinical studies.The most common grade 3/4 adverse events were neutropenia (23.1%), leukopenia (23.1%), and hyponatremia (23.1%).The etoposide concentrations in the CSF were much lower than those in plasma, and bevacizumab did not increase etoposide delivery to the CSF.

View Article: PubMed Central - PubMed

Affiliation: National Center of Excellence for Clinical Trial and Research, National Taiwan University Hospital, Taipei City, 10002, Taiwan. peifangwu@ntu.edu.tw.

ABSTRACT

Background: Elevated vascular endothelial growth factor (VEGF) was associated with poor prognosis in leptomeningeal carcinomatosis and anti-angiogenic therapy was found to prolong the survival of mice in preclinical studies. This prospective pilot study investigated the efficacy of anti-VEGF therapy plus chemotherapy in patients with leptomeningeal carcinomatosis originating from breast cancer.

Methods: Eligible patients were scheduled to receive bevacizumab combined with etoposide and cisplatin (BEEP) every 3 weeks for a maximum of 6 cycles or until unacceptable toxicity. The primary objective was the central nervous system (CNS)-specific response rate, which was defined as disappearance of cancer cells in the cerebrospinal fluid (CSF) and an improved or stabilized neurologic status. The impact of VEGF inhibition on etoposide penetration into the CSF was analyzed.

Results: Eight patients were enrolled. The CNS-specific response rate was 60% in 5 evaluable patients. According to intent-to-treat analysis, the median overall survival of the eight patients was 4.7 months (95% confidence interval, CI, 0.3-9.0) and the neurologic progression-free survival was 4.7 months (95% CI 0-10.5). The most common grade 3/4 adverse events were neutropenia (23.1%), leukopenia (23.1%), and hyponatremia (23.1%). The etoposide concentrations in the CSF were much lower than those in plasma, and bevacizumab did not increase etoposide delivery to the CSF.

Conclusions: BEEP exhibited promising efficacy in breast cancer patients with leptomeningeal carcinomatosis. Additional studies are warranted to verify its efficacy and clarify the role of anti-angiogenic therapy in this disease.

Trial registration: ClinicalTrials.gov identifying number NCT01281696 .

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Related in: MedlinePlus

The effects of bevacizumab administration on the temporal changes of CSF to plasma ratio of etoposide concentration. (A) Individual CSF/ Plasma ratio of etoposide concentration versus time plot. (B) Overall CSF/Plasma ratio of etoposide concentration versus time plot.
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Fig2: The effects of bevacizumab administration on the temporal changes of CSF to plasma ratio of etoposide concentration. (A) Individual CSF/ Plasma ratio of etoposide concentration versus time plot. (B) Overall CSF/Plasma ratio of etoposide concentration versus time plot.

Mentions: Four patients were subjected to serial measurements of etoposide concentrations in the CSF and plasma before and after bevacizumab administration. A plot of the individual ratio of the etoposide concentration in the CSF to that in the plasma versus time is shown in Figure 2A. We observed that bevacizumab administered 24 hours prior to the administration of cytotoxic drugs exerted no significant effects on etoposide penetration into the CSF (Figure 2B, P = .167, .680, .754, at 1 h, 2 h, and 6 h, respectively).Figure 2


A pilot study of bevacizumab combined with etoposide and cisplatin in breast cancer patients with leptomeningeal carcinomatosis.

Wu PF, Lin CH, Kuo CH, Chen WW, Yeh DC, Liao HW, Huang SM, Cheng AL, Lu YS - BMC Cancer (2015)

The effects of bevacizumab administration on the temporal changes of CSF to plasma ratio of etoposide concentration. (A) Individual CSF/ Plasma ratio of etoposide concentration versus time plot. (B) Overall CSF/Plasma ratio of etoposide concentration versus time plot.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4403836&req=5

Fig2: The effects of bevacizumab administration on the temporal changes of CSF to plasma ratio of etoposide concentration. (A) Individual CSF/ Plasma ratio of etoposide concentration versus time plot. (B) Overall CSF/Plasma ratio of etoposide concentration versus time plot.
Mentions: Four patients were subjected to serial measurements of etoposide concentrations in the CSF and plasma before and after bevacizumab administration. A plot of the individual ratio of the etoposide concentration in the CSF to that in the plasma versus time is shown in Figure 2A. We observed that bevacizumab administered 24 hours prior to the administration of cytotoxic drugs exerted no significant effects on etoposide penetration into the CSF (Figure 2B, P = .167, .680, .754, at 1 h, 2 h, and 6 h, respectively).Figure 2

Bottom Line: Elevated vascular endothelial growth factor (VEGF) was associated with poor prognosis in leptomeningeal carcinomatosis and anti-angiogenic therapy was found to prolong the survival of mice in preclinical studies.The most common grade 3/4 adverse events were neutropenia (23.1%), leukopenia (23.1%), and hyponatremia (23.1%).The etoposide concentrations in the CSF were much lower than those in plasma, and bevacizumab did not increase etoposide delivery to the CSF.

View Article: PubMed Central - PubMed

Affiliation: National Center of Excellence for Clinical Trial and Research, National Taiwan University Hospital, Taipei City, 10002, Taiwan. peifangwu@ntu.edu.tw.

ABSTRACT

Background: Elevated vascular endothelial growth factor (VEGF) was associated with poor prognosis in leptomeningeal carcinomatosis and anti-angiogenic therapy was found to prolong the survival of mice in preclinical studies. This prospective pilot study investigated the efficacy of anti-VEGF therapy plus chemotherapy in patients with leptomeningeal carcinomatosis originating from breast cancer.

Methods: Eligible patients were scheduled to receive bevacizumab combined with etoposide and cisplatin (BEEP) every 3 weeks for a maximum of 6 cycles or until unacceptable toxicity. The primary objective was the central nervous system (CNS)-specific response rate, which was defined as disappearance of cancer cells in the cerebrospinal fluid (CSF) and an improved or stabilized neurologic status. The impact of VEGF inhibition on etoposide penetration into the CSF was analyzed.

Results: Eight patients were enrolled. The CNS-specific response rate was 60% in 5 evaluable patients. According to intent-to-treat analysis, the median overall survival of the eight patients was 4.7 months (95% confidence interval, CI, 0.3-9.0) and the neurologic progression-free survival was 4.7 months (95% CI 0-10.5). The most common grade 3/4 adverse events were neutropenia (23.1%), leukopenia (23.1%), and hyponatremia (23.1%). The etoposide concentrations in the CSF were much lower than those in plasma, and bevacizumab did not increase etoposide delivery to the CSF.

Conclusions: BEEP exhibited promising efficacy in breast cancer patients with leptomeningeal carcinomatosis. Additional studies are warranted to verify its efficacy and clarify the role of anti-angiogenic therapy in this disease.

Trial registration: ClinicalTrials.gov identifying number NCT01281696 .

Show MeSH
Related in: MedlinePlus