Phase 1 study of the novel vascular disrupting agent plinabulin (NPI-2358) and docetaxel

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• 作者：Michael Millward (1)
  Paul Mainwaring (25)
  Alain Mita (3)
  Kristine Federico (4)
  G. K. Lloyd (4)
  Natasha Reddinger (4)
  Steffan Nawrocki (3)
  Monica Mita (3)
  Matthew A. Spear (4) mspear@nereuspharm.com
• 关键词：Angiogenesis – ; Docetaxel – ; Non ; small cell lung cancer (NSCLC) – ; Vascular disrupting agent (VDA) – ; Vascular targeting
• 刊名：Investigational New Drugs
• 出版年：2012
• 出版时间：June 2012
• 年：2012
• 卷：30
• 期：3
• 页码：1065-1073
• 全文大小：274.0 KB
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  28. Phase 1/2 Study of Vascular Disrupting Agent NPI-2358 + Docetaxel in Patients With Advanced Non-Small Cell Lung Cancer. http://www.clinicaltrials.gov/ct2/show/NCT00630110
• 作者单位：1. Department of Medical Oncology, Sir Charles Gairdner Hospital & University of Western Australia, Perth, Australia2. Division of Cancer Services, Mater Hospital, Brisbane, Australia3. Cancer Therapy and Research Center, Institute for Drug Development, San Antonio, TX, USA4. Nereus Pharmaceuticals, Inc, 10480 Wateridge Circle, San Diego, CA 92121, USA5. Haematology and Oncology Clinics of Australia, Brisbane, Australia
• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Oncology
  Pharmacology and Toxicology
  
• 出版者：Springer Netherlands
• ISSN：1573-0646

文摘

Background Plinabulin (NPI-2358) is a vascular disrupting agent (VDA) that destabilizes tumor vascular endothelial cell architecture resulting in selective collapse of established tumor vasculature producing anti-tumor activity alone or in combination with cytotoxic agents. The objective of this study was to assess the recommended Phase 2 dose (RP2D) of plinabulin combined with docetaxel. Patients and Methods Patients received 75 mg/m2 docetaxel on day 1 and plinabulin on days 1 and 8 intravenously in 21 day cycles. Plinabulin was escalated from the biologically effective dose (BED) of 13.5 mg/m2 to the standard single agent dose of 30 mg/m2 using a “3+3” design. Results Thirteen patients were enrolled. Adverse events were consistent with those of both agents alone. Fatigue, pain, nausea, diarrhea and vomiting were the most common events. One dose limiting toxicity of nausea, vomiting, dehydration and neutropenia occurred. The RP2D was 30 mg/m2 of plinabulin with 75 mg/m2 docetaxel. Pharmacokinetics did not indicate drug-drug interactions. Of the 8 patients with NSCLC evaluable for response, 2 achieved a partial response and 4 demonstrated lesser decreases in tumor measurements. Conclusions The combination of full doses of plinabulin and docetaxel is tolerable. With encouraging antitumor activity, this supported further development of this combination.