Total regression of brain metastases in non-small cell lung cancer patients harboring EGFR mutations treated with gefitinib without radiotherapy: two case reports

NSCLC with multiple brain metastases is associated with a poor outcome; the overall
median survival time of NSCLC was previously reported to be 3.5 months, while the
one-year survival rate was 10 % 4]. Therefore, treatment strategies for brain metastasis need to be commensurate with
the development of systemic treatments. Standard treatment options include symptomatic
therapy with WBRT. The use of conventional chemotherapy for brain metastases has been
limited because of a presumed lack of effectiveness due to poor penetration beyond
the BBB. The ideal characteristics of compounds with a higher probability of crossing
the BBB include a low molecular weight, a non-polar nature, and not being substrates
for efflux pumps 5]. Small molecules such as EGFR-TKIs have the ability to cross the BBB. Cappuzzo and
coworkers showed that EGFR-TKIs effectively penetrated the BBB because of their chemical
structures and low molecular weights 6]. Therefore, these EGFR-TKIs may be efficacious in the treatment of brain metastasis.

Sun and coworkers previously reported that cranial irradiation resulted in lower neurocognitive
function in patients without brain metastasis than in those in the observation group
7]. Furthermore, dose per fraction reductions in prophylactic cranial irradiation have
been suggested to avoid or reduce the late complications associated with WBRT 8]. Since NSCLC is a relatively radio-resistant malignancy, and WBRT induces late declines
in cognitive function, EGFR-TKIs may be a promising option for the treatment of central
nervous system metastasis from NSCLC.

Several recent reports described the safety and efficacy of gefitinib in patients
with EGFR mutation-positive NSCLC aged 70 years with poor PS 2]. Gefitinib and erlotinib are orally active EGFR-TKIs and show significant efficacy
in patients with advanced NSCLC 9]. Since the hematological toxicities of EGFR-TKIs are lower than those of cytotoxic
chemotherapy, they may be useful in the treatment of elderly patients and/or patients
with poor PS.

In conclusion, NSCLC patients with brain metastases generally have poor PS. Due to
its ability to reverse poor PS and achieve the total regression of brain metastases,
EGFR-TKI therapy may be a suitable treatment for brain metastasis in lung cancer with
an EGFR mutation, particularly in elderly patients with poor PS.