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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

Efficacy results: Overall Survival (OS) and neurologic progression free survival (PFS).
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Fig1: Efficacy results: Overall Survival (OS) and neurologic progression free survival (PFS).

Mentions: The 8 patients were subjected to a survival analysis according to the intent-to-treat analysis. The median OS was 4.7 months (95% CI 0.3–9.0; Figure 1). The responders of CSF cytology had a trend toward longer median overall survival (9.0 vs 2.9 months, P = 0.076). The OS of the 3 responders was 10.7, 9.0, and 4.7 months respectively. The neurologic PFS was 4.7 months (95% CI 0–10.5; Figure 1).Figure 1


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)

Efficacy results: Overall Survival (OS) and neurologic progression free survival (PFS).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig1: Efficacy results: Overall Survival (OS) and neurologic progression free survival (PFS).
Mentions: The 8 patients were subjected to a survival analysis according to the intent-to-treat analysis. The median OS was 4.7 months (95% CI 0.3–9.0; Figure 1). The responders of CSF cytology had a trend toward longer median overall survival (9.0 vs 2.9 months, P = 0.076). The OS of the 3 responders was 10.7, 9.0, and 4.7 months respectively. The neurologic PFS was 4.7 months (95% CI 0–10.5; Figure 1).Figure 1

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