- High-dose intravenous methotrexate (MTX), which crosses the blood-brain barrier, shows a favorable efficacy and toxicity profile in a small, uncontrolled phase 2 trial of patients with central nervous system (CNS) metastatic breast cancer (mBCa).
Why this matters
- Brain metastasis accounts for 10%-42% of mBCa.
- Standard of care, consisting of radiotherapy and surgery, only carries a median survival of
- Results of this trial are promising enough to warrant a trial with even higher-dose MTX.
- Phase 2 open-label, uncontrolled trial of single-group, high-dose intravenous MTX (3 g/m2) given to consecutive patients with CNS mBCa (n=22) seen at a university hospital in France (2004-2009).
- Time to progression (TTP) is the interval from first treatment and date of progressive disease or death.
- Funding: None.
- Patient composition: 50% hormone receptor (HR)-positive, 45% HR-negative, 9% triple-negative.
- Median follow-up, 11 months.
- CNS response to MTX:
- 9% partial response.
- 45% disease stabilization.
- 45% disease progression.
- Response to MTX at other metastatic sites:
- 39% disease stabilization.
- 61% disease progression.
- TTP: 2.1 (95% CI, 1.4-2.9) months.
- OS: 6.3 (95% CI, 1.8-10) months.
- No grade 5 toxicity.
- 18% had grade 3-4 hematological toxicity.
- Most common grade 3-4 nonhematological toxicities were serum hepatic transaminases (18%) and stomatitis (9%).
- Single-center, open-label, uncontrolled observational design.
- Small sample size.