title: Phase 1 study of the novel vascular disrupting agent plinabulin (NPI-2358) and docetaxel.
abstract: 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.
  
  
  METHODS
  Patients received 75 mg/m(2) 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/m(2) to the standard single agent dose of 30 mg/m(2) 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/m(2) of plinabulin with 75 mg/m(2) 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.
authors.affiliation: Department of Medical Oncology, Sir Charles Gairdner Hospital & University of Western Australia, Perth, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Millward
authors.forename: Paul
authors.initials: P
authors.lastname: Mainwaring
authors.forename: Alain
authors.initials: A
authors.lastname: Mita
authors.forename: Kristine
authors.initials: K
authors.lastname: Federico
authors.forename: G K
authors.initials: GK
authors.lastname: Lloyd
authors.forename: Natasha
authors.initials: N
authors.lastname: Reddinger
authors.forename: Steffan
authors.initials: S
authors.lastname: Nawrocki
authors.forename: Monica
authors.initials: M
authors.lastname: Mita
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Spear
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects* / Q000493:pharmacokinetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism; D003967:Diarrhea / Q000139:chemically induced; D054659:Diketopiperazines / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D000077143:Docetaxel; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009503:Neutropenia / Q000139:chemically induced; D010146:Pain / Q000139:chemically induced; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D014839:Vomiting / Q000139:chemically induced
chemical_list: D054659:Diketopiperazines; C514351:NPI 2358; D043823:Taxoids; D000077143:Docetaxel