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Blood-brain barrier permeability of gefitinib in patients with brain metastases from non-small-cell lung cancer before and during whole brain radiation therapy.

Zeng YD, Liao H, Qin T, Zhang L, Wei WD, Liang JZ, Xu F, Dinglin XX, Ma SX, Chen LK - Oncotarget (2015)

Bottom Line: The CSF-to-plasma ratio of gefitinib increased with the increased dose of WBRT and reached the peak (1.87 ± 0.72%) at 30 Gy, which was significantly higher than that 1.34 ± 0.49% at 0 Gy (P = 0.01).The median time to progression of brain lesions and the median overall survival were 7.07 and 15.4 months, respectively.The BBB permeability of gefitinib increased in accordance with escalated dose of WBRT.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.

ABSTRACT

Introduction: To explore the ability of gefitinib to penetrate blood brain barrier (BBB) during whole brain radiation therapy (WBRT).

Patients and methods: Enrolled in this study were eligible patients who were diagnosed with BM from NSCLC. Gefitinib was given at 250 mg/day for 30 days, then concurrently with WBRT (40 Gy/20 F/4 w), followed by maintenance. Serial CSF and blood samples were collected on 30 day after gefitinib administration, and at the time of 10, 20, 30 and 40 Gy following WBRT. CSF and plasma samples of 13 patients without BM who were treated with gefitinib were collected as control. CSF and plasma gefitinib levels were measured by LC-MS/MS.

Results: Fifteen BM patients completed gefitinib plus WBRT. The CSF-to-plasma ratio of gefitinib in patients with BM was higher than that in patients without BM (1.34% vs. 0.36%, P < 0.001). The CSF-to-plasma ratio of gefitinib increased with the increased dose of WBRT and reached the peak (1.87 ± 0.72%) at 30 Gy, which was significantly higher than that 1.34 ± 0.49% at 0 Gy (P = 0.01). The median time to progression of brain lesions and the median overall survival were 7.07 and 15.4 months, respectively.

Conclusion: The BBB permeability of gefitinib increased in accordance with escalated dose of WBRT.

No MeSH data available.


Related in: MedlinePlus

(A) Correlation between plasma and CSF concentrations of gefitinib in 15 patients with BM. A good correlation (R2 = 0.57) was demonstrated (P = 0.001). (B) Correlation between plasma and CSF concentrations of gefitinib in 13 patients without BM. A good correlation (R2 = 0.70) was demonstrated (P = 0.004).
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Figure 2: (A) Correlation between plasma and CSF concentrations of gefitinib in 15 patients with BM. A good correlation (R2 = 0.57) was demonstrated (P = 0.001). (B) Correlation between plasma and CSF concentrations of gefitinib in 13 patients without BM. A good correlation (R2 = 0.70) was demonstrated (P = 0.004).

Mentions: The plasma concentrations of gefitinib were similar between patients with and without BM. Both the mean CSF concentration of gefitinib and the CSF-to-plasma ratio of gefitinib in patients with BM were significantly higher than those in patients without BM (Table 2, P < 0.001). A good correlation (R2 = 0.57) between plasma and CSF concentrations of gefitinib in 15 patients with BM before WBRT was demonstrated (P = 0.001, Figure 2A). Similarly, a good correlation (R2=0.70) between plasma and CSF concentrations of gefitinib was demonstrated in 13 patients without BM (P = 0.004, Figure 2B). The CSF concentration of gefitinib and the CSF-to-plasma ratio increased with escalation of the WBRT dose (Figure 3A, 3B). The mean CSF concentration of gefitinib at 30 and 40 Gy was statistically higher than that at 0 Gy. The CSF-to-plasma ratio of gefitinib reached the peak (1.87 ± 0.72%) at 30 Gy, which was significantly higher than 1.34 ± 0.49% at 0 Gy (P = 0.01). Pharmacokinetic analysis indicated that the addition of WBRT enhanced gefitinib's ability of penetration in CSF.


Blood-brain barrier permeability of gefitinib in patients with brain metastases from non-small-cell lung cancer before and during whole brain radiation therapy.

Zeng YD, Liao H, Qin T, Zhang L, Wei WD, Liang JZ, Xu F, Dinglin XX, Ma SX, Chen LK - Oncotarget (2015)

(A) Correlation between plasma and CSF concentrations of gefitinib in 15 patients with BM. A good correlation (R2 = 0.57) was demonstrated (P = 0.001). (B) Correlation between plasma and CSF concentrations of gefitinib in 13 patients without BM. A good correlation (R2 = 0.70) was demonstrated (P = 0.004).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4480758&req=5

Figure 2: (A) Correlation between plasma and CSF concentrations of gefitinib in 15 patients with BM. A good correlation (R2 = 0.57) was demonstrated (P = 0.001). (B) Correlation between plasma and CSF concentrations of gefitinib in 13 patients without BM. A good correlation (R2 = 0.70) was demonstrated (P = 0.004).
Mentions: The plasma concentrations of gefitinib were similar between patients with and without BM. Both the mean CSF concentration of gefitinib and the CSF-to-plasma ratio of gefitinib in patients with BM were significantly higher than those in patients without BM (Table 2, P < 0.001). A good correlation (R2 = 0.57) between plasma and CSF concentrations of gefitinib in 15 patients with BM before WBRT was demonstrated (P = 0.001, Figure 2A). Similarly, a good correlation (R2=0.70) between plasma and CSF concentrations of gefitinib was demonstrated in 13 patients without BM (P = 0.004, Figure 2B). The CSF concentration of gefitinib and the CSF-to-plasma ratio increased with escalation of the WBRT dose (Figure 3A, 3B). The mean CSF concentration of gefitinib at 30 and 40 Gy was statistically higher than that at 0 Gy. The CSF-to-plasma ratio of gefitinib reached the peak (1.87 ± 0.72%) at 30 Gy, which was significantly higher than 1.34 ± 0.49% at 0 Gy (P = 0.01). Pharmacokinetic analysis indicated that the addition of WBRT enhanced gefitinib's ability of penetration in CSF.

Bottom Line: The CSF-to-plasma ratio of gefitinib increased with the increased dose of WBRT and reached the peak (1.87 ± 0.72%) at 30 Gy, which was significantly higher than that 1.34 ± 0.49% at 0 Gy (P = 0.01).The median time to progression of brain lesions and the median overall survival were 7.07 and 15.4 months, respectively.The BBB permeability of gefitinib increased in accordance with escalated dose of WBRT.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.

ABSTRACT

Introduction: To explore the ability of gefitinib to penetrate blood brain barrier (BBB) during whole brain radiation therapy (WBRT).

Patients and methods: Enrolled in this study were eligible patients who were diagnosed with BM from NSCLC. Gefitinib was given at 250 mg/day for 30 days, then concurrently with WBRT (40 Gy/20 F/4 w), followed by maintenance. Serial CSF and blood samples were collected on 30 day after gefitinib administration, and at the time of 10, 20, 30 and 40 Gy following WBRT. CSF and plasma samples of 13 patients without BM who were treated with gefitinib were collected as control. CSF and plasma gefitinib levels were measured by LC-MS/MS.

Results: Fifteen BM patients completed gefitinib plus WBRT. The CSF-to-plasma ratio of gefitinib in patients with BM was higher than that in patients without BM (1.34% vs. 0.36%, P < 0.001). The CSF-to-plasma ratio of gefitinib increased with the increased dose of WBRT and reached the peak (1.87 ± 0.72%) at 30 Gy, which was significantly higher than that 1.34 ± 0.49% at 0 Gy (P = 0.01). The median time to progression of brain lesions and the median overall survival were 7.07 and 15.4 months, respectively.

Conclusion: The BBB permeability of gefitinib increased in accordance with escalated dose of WBRT.

No MeSH data available.


Related in: MedlinePlus