Upfront association of carboplatin plus pemetrexed in patients with brain metastases of lung adenocarcinoma

Abstract

Approximately 10% of patients with non-small cell lung cancer (NSCLC) have brain metastases at the time of diagnosis. When surgical resection is not possible, whole brain radiotherapy is the standard of care, with a cerebral response rate of approximately 30%. We report our experience with an upfront association of carboplatin and pemetrexed (areas under the curve, 5 and 500 mg/m 2 , respectively), every 3 weeks, in 30 patients presenting with newly diagnosed brain metastases and NSCLC. Cerebral MRIs were performed every 6 -9 weeks. The radiologic response rates were assessed according to Response Evaluation Criteria in Solid Tumors. Overall survival was also determined. Twenty-six patients were evaluable for response, and the objective cerebral response rate (complete and partial response) in the intent-to-treat population was 40% (12 of 30 patients). Event-free survival was 31 weeks, and median overall survival was 39 weeks. The upfront association of carboplatin plus pemetrexed allows simultaneous treatment of cerebral and systemic disease in patients with NSCLC with newly diagnosed brain metastases and appears to be particularly interesting in terms of radiologic response and overall survival. Further clinical studies are warranted.

Bevacizumab, pemetrexed and carboplatin in first-line treatment of non-small cell lung cancer patients: Focus on patients with brain metastases

“…The median OS time was 10 months. The results of these three studies indicate that pemetrexed is a good treatment option in such patients (29)(30)(31).…”

“…For pemetrexed, data regarding patients with BM have been published in the first-and second-line settings. A response rate of 40% for newly diagnosed BM was reported by Bailon et al (2012) (29) in 30 patients with non-squamous NSCLC following first-line therapy with pemetrexed plus carboplatin. The median OS time was 39 weeks (29).…”

“…A response rate of 40% for newly diagnosed BM was reported by Bailon et al (2012) (29) in 30 patients with non-squamous NSCLC following first-line therapy with pemetrexed plus carboplatin. The median OS time was 39 weeks (29). In a phase II study by Barlesi et al (2011) (30), first-line therapy with pemetrexed plus cisplatin resulted in an overall RR of 34.9% (95% CI, 21-50.9) and a disease control rate of 72.1% (overall response plus SD rate).…”

Epidermal growth factor receptor tyrosine kinase inhibitors for the treatment of central nervous system metastases from non-small cell lung cancer: the present and the future

“…This phenomenon could support the use of upfront chemotherapy for BM that damage the integrity of the barrier (15,16). First line upfront platinum based chemotherapy has been evaluated in different prospective trials and an objective response rate (ORR) of 23-50% was reported (5,(17)(18)(19)(20)(21)(22)(23)(24). Pemetrexed and temozolomide showed some activity (25-29) while 5-FU, topotecan and vinorelbine, did not show any improvement in ORR and OS (23,30,31).…”

Risk factors of brain metastasis of lung squamous cell carcinoma: a retrospective analysis of 188 patients from single center

“…However, most patients die from systemic disease rather than intracranial failure. Systemic treatment with novel agents, such as tyrosine kinase inhibitors (TKIs) and pemetrexed, has been shown to be beneficial in patients with BM [14][15][16][17][18]. They could not only shrink the intracranial lesions, but also prolong the survival.…”