Kazuhiro Usui1, Shunichi Sugawara2, Masaru Nishitsuji3, Yuka Fujita4, Akira Inoue5, Atsuto Mouri6, Hiroshi Watanabe7, Hiroshi Sakai8, Ichiro Kinoshita9, Yoshihito Ohhara10, Makoto Maemondo11, Hiroshi Kagamu12, Koichi Hagiwara13, Kunihiko Kobayashi14. 1. Division of Respirology, NTT Medical Center Tokyo, 5-9-22 Higashigotanda, Shinagawa, Tokyo, Japan. Electronic address: usui@east.ntt.co.jp. 2. Department of Pulmonary Medicine, Sendai Kousei Hospital, Japan. 3. Department of Respiratory Medicine, Ishikawa Prefectural Central Hospital, Japan. 4. Department of Respiratory Medicine, National Hospital Organization Asahikawa Medical Center, Japan. 5. Department of Respiratory Medicine, Tohoku University Hospital, Japan. 6. Department of Pulmonology, National Hospital Organization Disaster Medical Center, Japan. 7. Department of Respiratory medicine, Saka General Hospital, Japan. 8. Department of Thoracic Oncology, Saitama Cancer Center, Japan. 9. Department of Medical Oncology, Hokkaido University Graduate School of Medicine, Japan. 10. Department of Medical Oncology, KKR Sapporo Medical Center, Japan. 11. Department of Respiratory Medicine, Miyagi Cancer Center, Japan. 12. Department of Respiratory Medicine and Infectious Disease, Niigata University Medical and Dental Hospital, Japan. 13. Department of Comprehensive Medicine 1, Saitama Medical Center Jichi University, Japan. 14. Department of Respiratory medicine, Saitama International Medical Center, Saitama Medical University, Japan.
Abstract
BACKGROUND: Vascular endothelial growth factor (VEGF) plays a pivotal role in the pathogenesis of malignant pleural effusion (MPE). Here, a multicenter phase II trial to evaluate bevacizumab in non-squamous non-small cell lung carcinoma patients with MPE was conducted. METHODS: Patients having MPE with no prior treatment and performance status of 0-2 received carboplatin (area under the curve: AUC 6; up to 6 cycles) and pemetrexed (500mg/m(2)) with bevacizumab (15mg/kg) every 3 weeks. The primary endpoint was the control rate of MPE without pleurodesis at 8 weeks after treatment. VEGF levels in plasma and MPE were measured by enzyme immunoassay. RESULTS: Of 30 patients entered (median 66 years; 24 males; adenocarcinoma; 4 epidermal growth factor receptor: EGFR mutations), 28 patients (2 withdrawn patients) were given a median of 4 cycles of carboplatin, and 68% of the patients received maintenance pemetrexed with bevacizumab (median 8 cycles). At eight weeks, MPE was controlled without pleurodesis in 93% of treated patients (95% confidence interval: 77-99%). At the median follow-up time of 12.8 months, 78.6% of the cases required no pleurodesis. Response rate was 46%, and median progression-free survival (PFS) and overall survival (OS) were 8.2 months and 18.6 months, respectively. Toxicities of grade ≥3 included neutropenia (28.6%), thrombocytopenia (28.6%), proteinuria (3.6%), and hypertension (3.6%). Assessment of VEGF levels before treatment indicated that patients with low VEGF (<1000pg/ml) in MPE frequently needed pleurodesis (p=0.011), and that high VEGF (≥100pg/ml) in plasma was indicative of poor prognosis in the context of PFS (p=0.012). CONCLUSION: The combination of bevacizumab with carboplatin and pemetrexed demonstrated efficacy with acceptable toxicities in patients with MPE.
BACKGROUND:Vascular endothelial growth factor (VEGF) plays a pivotal role in the pathogenesis of malignant pleural effusion (MPE). Here, a multicenter phase II trial to evaluate bevacizumab in non-squamous non-small cell lung carcinomapatients with MPE was conducted. METHODS:Patients having MPE with no prior treatment and performance status of 0-2 received carboplatin (area under the curve: AUC 6; up to 6 cycles) and pemetrexed (500mg/m(2)) with bevacizumab (15mg/kg) every 3 weeks. The primary endpoint was the control rate of MPE without pleurodesis at 8 weeks after treatment. VEGF levels in plasma and MPE were measured by enzyme immunoassay. RESULTS: Of 30 patients entered (median 66 years; 24 males; adenocarcinoma; 4 epidermal growth factor receptor: EGFR mutations), 28 patients (2 withdrawn patients) were given a median of 4 cycles of carboplatin, and 68% of the patients received maintenance pemetrexed with bevacizumab (median 8 cycles). At eight weeks, MPE was controlled without pleurodesis in 93% of treated patients (95% confidence interval: 77-99%). At the median follow-up time of 12.8 months, 78.6% of the cases required no pleurodesis. Response rate was 46%, and median progression-free survival (PFS) and overall survival (OS) were 8.2 months and 18.6 months, respectively. Toxicities of grade ≥3 included neutropenia (28.6%), thrombocytopenia (28.6%), proteinuria (3.6%), and hypertension (3.6%). Assessment of VEGF levels before treatment indicated that patients with low VEGF (<1000pg/ml) in MPE frequently needed pleurodesis (p=0.011), and that high VEGF (≥100pg/ml) in plasma was indicative of poor prognosis in the context of PFS (p=0.012). CONCLUSION: The combination of bevacizumab with carboplatin and pemetrexed demonstrated efficacy with acceptable toxicities in patients with MPE.
Authors: Erika Penz; Kristina N Watt; Christopher A Hergott; Najib M Rahman; Ioannis Psallidas Journal: Cancer Manag Res Date: 2017-06-23 Impact factor: 3.989