Limits...
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

Comparison of overall survival (A) and progression-free survival (B) between patients with BM from NSCLC according to EGFR mutation statusComparison of time to progression of brain lesions (C) and lung lesions (D) from patients with BM from NSCLC according to EGFR mutation status.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4480758&req=5

Figure 4: Comparison of overall survival (A) and progression-free survival (B) between patients with BM from NSCLC according to EGFR mutation statusComparison of time to progression of brain lesions (C) and lung lesions (D) from patients with BM from NSCLC according to EGFR mutation status.

Mentions: The treatment response and survival analysis of the 15 patients according to the EGFR mutation status were shown in Table 3. The median PFS and OS in patients with EGFR mutations were significantly longer, compared with patients with EGFR wild type (P < 0.05, Figure 4A, 4B). The median TTP of either brain lesions or primary lung lesions was significantly longer in EGFR mutant patients (P < 0.05) (Figure 4C, 4D). In addition, the RR of BM was higher in patients with EGFR mutant disease than that in patients with wild-type disease (83.33% vs.11.11%) (Table 4).


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)

Comparison of overall survival (A) and progression-free survival (B) between patients with BM from NSCLC according to EGFR mutation statusComparison of time to progression of brain lesions (C) and lung lesions (D) from patients with BM from NSCLC according to EGFR mutation status.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: Comparison of overall survival (A) and progression-free survival (B) between patients with BM from NSCLC according to EGFR mutation statusComparison of time to progression of brain lesions (C) and lung lesions (D) from patients with BM from NSCLC according to EGFR mutation status.
Mentions: The treatment response and survival analysis of the 15 patients according to the EGFR mutation status were shown in Table 3. The median PFS and OS in patients with EGFR mutations were significantly longer, compared with patients with EGFR wild type (P < 0.05, Figure 4A, 4B). The median TTP of either brain lesions or primary lung lesions was significantly longer in EGFR mutant patients (P < 0.05) (Figure 4C, 4D). In addition, the RR of BM was higher in patients with EGFR mutant disease than that in patients with wild-type disease (83.33% vs.11.11%) (Table 4).

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