State of the art of chemotherapy for the treatment of central nervous system metastases from non-small cell lung cancer

Abstract

Chemotherapy is the mainstay of treatment of advanced non-small cell lung cancer (NSCLC) without molecular drivers. Despite a low penetration of central nervous system (CNS), chemotherapy drugs demonstrated encouraging activity against CNS metastases from NSCLC. Based on the available data, chemotherapy should be considered as an important part of the multidisciplinary treatment of CNS metastases. Particularly, platinum-based regimens represent the most active combinations and pemetrexed is associated with a meaningful clinical benefit for patients with non-squamous histology. How to integrate chemotherapy and radiotherapy for newly diagnosed brain metastases (BMs) is still debated. Although flawed by some limitations, the available evidence suggests a role for upfront chemotherapy for the treatment of NSCLC patients with synchronous, asymptomatic BMs, thus allowing a delay of radiotherapy. Despite the introduction of modern and more effective chemotherapy, however, the prognosis of NSCLC patients with CNS metastases remains poor, especially for those with progressive BMs or leptomeningeal carcinomatosis (LC).

Endostar (rh‐endostatin) versus placebo in combination with vinorelbine plus cisplatin chemotherapy regimen in treatment of advanced non‐small cell lung cancer: A meta‐analysis

“…Platinum‐based chemotherapy is currently considered the first‐line treatment regimen for advanced NSCLC patients . Efficacy and long‐term survival rates in patients treated with a combined chemotherapy regimen are greater than in those administered a non‐platinum chemotherapy regimen; however, the difference according to previously published prospective randomized clinical trials and high quality meta‐analysis was not statistically significant …”

Genetic heterogeneity and evolutionary history of high-grade ovarian carcinoma and matched distant metastases

“…Despite the fact that patient OVA_378 also demonstrates linear progression, all sampled regions were treatment naive, where the primary and synchronous metastatic tumours continued to clonally expand in parallel converging on driver gene FLNA in late clonal expansions irrespective of therapeutic pressures. Since previous studies have shown carboplatin treatment having limited blood-brain barrier (BBB) penetration (2.6%) and subsequently minimal therapeutic effect in brain metastases, despite its ability to penetrate abnormal BBB, 27 the evolutionary processes in the brain metastasis (OVA_048) were less likely to be affected or shaped by the carboplatin treatment, with all metastatic clones reaching near 100% CCFs. Interestingly, one patient (OVA_003) acquired all somatic mutations in the metastatic tumour from the primary tumour, with no further clonal expansion, even after 20 months, post therapy.…”

CNS metastasis secondary to malignant-mixed Müllerian tumor: case report and review of therapeutics

“…In clinical trials for CNS metastases from lung cancer, cisplatin-paclitaxel and carboplatin-paclitaxel regimens have both demonstrated intracranial RRs comparable to systemic RRs, despite limited CNS penetrance [36][37][38]. This suggests a meaningful role for platinum-based chemotherapy in the treatment of MMMT.…”