| General information |
| Database: | DB00873 |
| Objective: | they hypothesized that a window period between bevacizumab and cytotoxic agents may enhance drug delivery into tumor tissue through bevacizumabinduced vascular normalization in patients with brain metastases of breast cancer (BMBC). |
| Authors: | Lu YS, et al |
| Title: | Bevacizumab preconditioning followed by Etoposide and Cisplatin is highly effective in treating brain metastases of breast cancer progressing from wholebrain radiotherapy. |
| Journal: | Clin Cancer Res. |
| Year: | 2015 |
| PMID: | 25700303 |
| Trial Design |
| Clinical Trial Id: | NCT01281696 |
| Agent: | bevacizumab
|
| Target: | Vascular endothelial growth factor
|
| Cancer Type: | breast cancer |
| Cancer Subtype: | advanced breast cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | Bevacizumab preconditioning followed by Etoposide + Cisplatin |
| Study Type: | A singlearmphase II study |
| Key Patients Feature: | patients with brain metastases of breast cancer who were refractory to wholebrain radiotherapy |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | In a 21day cycle, patients received bevacizumab (15 mg/kg) on day 1, which, with a 1day window period, was followed by etoposide (70 mg/m(2)/day; days 24) and cisplatin (70 mg/m(2); day 2; BEEP regimen). The BEEP regimen was administered for a maximum of 6 cycles. |
| Primary End Point: | the central nervous system (CNS)objective response rate according to volumetric response criteria |
| Secondary End Point: | NA |
| Patients Number: | 35 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | 77.10% |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 6.1 months (95% CI, 5.0-7.2) |
| Median OS A vs. C: | 10.5 months (95% CI, 7.813.2) |
| Adverse Event(agent arm): | Table 2 presents a summary of the toxicity profile. Hematologic toxicity was a primary concern, but was generally manageable. Nonhematologic toxicity was generally mild. Two patients died: one of infection and one of a tracheoesophageal fistula. The patient with tracheoesophageal fistula presented with extensive mediastinal lymph node metastases between the esophagus and trachea at the baseline, but the CNS tumors completely resolved after 3 cycles of the BEEP treatment. Because of the high incidence of grade 3 or 4 neutropenia, they amended the protocol to mandate prophylactic filgrastim (300 ¦Ìg/day) treatment starting 3 days after the administration of the BEEP. After the amendment, the incidence of grade 3 or 4 neutropenia decreased from 37% to 12% per cycle. |
| Conclusions: | By administering bevacizumab 1 day before etoposide and cisplatin, the BEEP regimen appeared highly effective in BMBC refractory to WBRT. Further study of vascular normalization window concept is warranted. |