Pemetrexed and cisplatin as first-line chemotherapy for advanced non-small-cell lung cancer (NSCLC) with asymptomatic inoperable brain metastases: a multicenter phase II trial (GFPC 07-01)

Barlési, Fabrice; Gervais, Radj; Léna, H.; Hureaux, J.; Bérard, H.; Paillotin, D.; Bota, S.; Monnet, I.; Chajara, Abdesslam; Robinet, G.

doi:10.1093/annonc/mdr003

Cited by 203 publications

(145 citation statements)

References 14 publications

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“…This study reported that the PFS time was significantly extended following maintenance therapy with BEV plus PEM and that the patients exhibited a high tolerability to this therapeutic regime (21). However, the dose of BEV used in the AVAPERL study was 7.5 mg/kg (a commonly used dose in Europe).…”

Section: Introductionmentioning

confidence: 99%

Feasibility of cisplatin/pemetrexed with 15 mg/kg bevacizumab for the treatment of patients with advanced non-squamous non-small cell lung cancer

et al. 2015

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Abstract. The aim of the present study was to retrospectively evaluate the feasibility of cisplatin/pemetrexed/bevacizumab (CPB) therapy at a bevacizumab (BEV) dose of 15 mg/kg as a first-line chemotherapeutic strategy for patients with advanced non-squamous non-small cell lung cancer (NSCLC). A total of 31 consecutive patients with non-squamous NSCLC were treated with first-line chemotherapy of CPB at a BEV dose of 15 mg/kg at the National Kyushu Cancer Center (Fukuoka, Japan) between November 2009 and December 2011. Clinical characteristics, response rate (RR), progression-free survival (PFS) time, overall survival (OS) time and adverse events were retrospectively analyzed. The 31 patients exhibited a male:female ratio of 21:10 and a median age of 60 years (range, 38-76 years). In total, 5 patients were of clinical stage III and 26 patients were of stage IV, 15 had a performance status of 0 and 16 had a performance status of 1, and 29 patients were diagnosed with adenocarcinoma and 2 were diagnosed with adenosquamous carcinoma. The EGFR mutation status was positive (exon 19 deletion), wild-type and unknown in 3, 21 and 7 patients, respectively. A total of 28 patients (90.3%) received a minimum of four courses of CPB therapy. Hematological toxicities classified as grade III or higher included neutropenia (29.0%), anemia (3.2%) and thrombocytopenia (3.2%), however, no severe non-hematological toxicities were observed. Additionally, 22 patients (71.0%) exhibited a partial response and 9 (29.0%) exhibited stable disease, resulting in a RR of 71.0% [95% confidence interval (CI), . The median PFS and OS times were 8.4 months (95% CI, 7.9-9.0) and 28.5 months (95% CI, 26.4-30.6), respectively. Therefore, CPB therapy at a BEV dose of 15 mg/kg appears to be a feasible treatment strategy for patients with advanced non-squamous NSCLC. IntroductionAt present, the standard first-line chemotherapy for patients with advanced non-small cell lung cancer (NSCLC) is platinum doublet chemotherapy using a third-generation anticancer agent (1,2). Pemetrexed (PEM) is a novel metabolic antagonist capable of inhibiting multiple enzymes involved in folate metabolism that has been clinically introduced as an effective therapeutic agent in the treatment of NSCLC (3-5). Previously, the results of two phase III studies indicated the efficacy of PEM as a first-line therapy for advanced NSCLC (6,7). In the JMDB study, cisplatin (CDDP) plus PEM therapy was not determined to be inferior to CDDP plus gemcitabine (GEM) therapy in terms of the overall survival (OS), and the incidence of severe adverse events was significantly lower following CDDP plus PEM therapy (6). Furthermore, in a subgroup analysis according to histological type, the OS of patients with non-squamous NSCLC was significantly longer in the CDDP plus PEM therapy group compared with the CDDP plus GEM group. In addition, the effectiveness of PEM for the treatment of non-squamous NSCLC was supported by two of the phase III studies (JMEI and JMEN) (8,9). Thus, at present, CDDP plus ...

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Section: Introductionmentioning

confidence: 99%

Feasibility of cisplatin/pemetrexed with 15 mg/kg bevacizumab for the treatment of patients with advanced non-squamous non-small cell lung cancer

et al. 2015

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“…Pemetrexed, a multi-targeted antifolate drug, has been demonstrated in vitro to inhibit at least three different enzymes involved in the human folate pathway including thymidylate synthase (TS), dihydrofolate reductase (DHFR) and glycinamide ribonucleotide formyl transferase (4,5). These enzymes are involved in the synthesis of nucleotides, and ultimately pemetrexed is capable of interfering with RNA and DNA synthesis procedures (6).…”

Section: Introductionmentioning

confidence: 99%

Efficacy assessment of pemetrexed treatment of an NSCLC case with brain metastasis

et al. 2012

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Abstract. Non-small cell lung cancers (NSCLCs) are among the most common malignancies. Although pemetrexed is often used clinically to cure cancers, its efficacy in NSCLC patients with progressive brain metastases remains unclear. Here, we report a successful NSCLC (adenocarcinoma) case treated with pemetrexed. The detected tumors were treated with 900 mg of pemetrexed disodium (500 mg/m 2 ) was administered to the patient on day 1, and 40 mg of cisplatin (25mg/m 2 ) was administered on days 1-3, at the interval of 3 weeks. After two cycles of chemotherapy, the brain metastases were reduced. The lesion in the lung was reduced as determined by chest CT-scan. Our results suggest that pemetrexed is an effective therapy for patients with NSCLC and progressive brain metastases.

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“…Subsequent studies demonstrated that the addition of platinum compounds to pemetrexed can slightly improve the outcome. In a phase 2 trial on 43 chemotherapy naïve NSCLC with BMs (93% with nonsquamous histology) treated with pemetrexed and cisplatin at standard doses for six cycles, the intracranial RR was 41.9% (50). A comparable intracranial RR of 40% was obtained when pemetrexed was combined with carboplatin, as reported by an observational study on 30 patients with NSCLC adenocarcinoma and BMs (51) ( Table 2).…”

Section: Clinical Activity Of Chemotherapy Against Bms From Nsclcmentioning

confidence: 60%

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

Inno¹,

Noia²,

D’Argento³

et al. 2016

Transl. Lung Cancer Res.

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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).

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Pemetrexed and cisplatin as first-line chemotherapy for advanced non-small-cell lung cancer (NSCLC) with asymptomatic inoperable brain metastases: a multicenter phase II trial (GFPC 07-01)

Abstract: Pemetrexed-cisplatin is an effective and well-tolerated regimen as first-line therapy for NSCLC patients with BM who always suffer a poor prognosis.

Cited by 203 publications

References 14 publications

Feasibility of cisplatin/pemetrexed with 15 mg/kg bevacizumab for the treatment of patients with advanced non-squamous non-small cell lung cancer

Feasibility of cisplatin/pemetrexed with 15 mg/kg bevacizumab for the treatment of patients with advanced non-squamous non-small cell lung cancer

Efficacy assessment of pemetrexed treatment of an NSCLC case with brain metastasis

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

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