In a phase II study in which 28 subjects were treated with carboplatin + pemetrexed + bevacizumab, the pleural effusion control rate was 93%,5 and in a phase II study in which 23 subjects were treated with carboplatin + paclitaxel + bevacizumab, the pleural effusion control rate was 87%

In a phase II study in which 28 subjects were treated with carboplatin + pemetrexed + bevacizumab, the pleural effusion control rate was 93%,5 and in a phase II study in which 23 subjects were treated with carboplatin + paclitaxel + bevacizumab, the pleural effusion control rate was 87%.6 In the former study, anemia (CTCAE grade 3 or higher) was reported in 25% of subjects, while in the latter febrile neutropenia was seen in 26% of cases. the age\adjusted mortality rate of lung cancer has gradually, but steadily, decreased in males while remaining the Magnolol same in females.2 The prognosis of lung cancer patients with malignant pleural effusion (MPE) GDNF due to carcinomatous pleurisy is said to be poor. An investigation into the clinical effects of the accumulation of MPE in 490 lung cancer patients reported that 40% of patients had MPE and that the overall survival (OS) of patients with MPE was 5.5?months. Furthermore, 79 out of 94 patients (84%) with MPE underwent treatment for MPE (pleural effusion drainage or pleural effusion catheter placement) to relieve their symptoms, and it was reported that palliative MPE treatment was necessary if the volume of MPE was equivalent to 50% of the volume of the thoracic cavity.3 The Lung Cancer Diagnosis and Treatment Guidelines of the Japan Lung Cancer Society recommend pleurodesis for carcinomatous pleurisy that has been treated with thoracic cavity drainage. Meta\analyses comparing various drugs showed that talc controlled MPE better than bleomycin, doxycycline, and tetracycline.4 Since the approval of the talc suspension method in 2013, talc, which has been shown to be able to control MPE, has been used universally in Japan. However, performing pleurodesis can cause patients’ performance status (PS) to worsen, Magnolol prolong sustained drainage, and delay the introduction of systemic drug therapy. Thus, effective and safe treatments for MPE are needed. It has been reported that bevacizumab, an antivascular endothelial growth factor (VEGF) antibody, was effective in non\small cell lung cancer (NSCLC) patients with MPE in two randomized studies in Japan.5, 6 However, there are no data to suggest that Magnolol ramucirumab, an anti\VEGF antibody that is used in the clinical setting, has the same effect. We decided to conduct a phase II, multicenter, single\arm interventional study to evaluate the effectiveness and safety of ramucirumab as a treatment for MPE. Methods Objectives The primary objective of this study is to evaluate the MPE control rate at eight weeks after the start of treatment with ramucirumab in combination with docetaxel (ramucirumab + docetaxel) in previously treated NSCLC patients with MPE. The secondary objectives of the study are to evaluate the efficacy of ramucirumab + docetaxel, in terms of its effects on the objective response rate, progression\free survival (PFS), one\year survival rate, and OS, as well as its toxicity profile. Study design The study protocol was reviewed and approved by Nagasaki University Clinical Research Review Committee (CRB7180001) (registration No. jRCTs071190013). Clinical hypothesis and phase setting of the study The clinical hypothesis underlying this study is that, Combined treatment using docetaxel and ramucirumab is safe, even for NSCLC patients with MPE, and will show a certain ability to control pleural effusion. Therefore, this will be a phase II study which examines the effects and safety of administering ramucirumab + docetaxel to NSCLC patients with MPE (Fig. ?(Fig.1).1). This study was sponsored by Eli Lilly Company. Open in a separate window Figure 1 Study schema. Inclusion and exclusion criteria Inclusion criteria: (i) The patient has provided written consent after receiving a sufficient explanation about the study prior to enrollment; (ii) The patient is 20?years old on the day of enrollment; (iii) The patient has histologically\ or cytologically\confirmed NSCLC; (iv) The patient has clinical stage IV disease; (v) The patient exhibited disease progression during or after prior treatment with one (and only one) platinum\based chemotherapy regimen with or without maintenance therapy for advanced/metastatic disease.