title: Phase II study of plitidepsin 3-hour infusion every 2 weeks in patients with unresectable advanced medullary thyroid carcinoma.
abstract: OBJECTIVE
  To evaluate the antitumor response, time-to-event efficacy endpoints and toxicity of plitidepsin (Aplidin) 5 mg/m as a 3-hour intravenous (i.v.) infusion every 2 weeks in patients with unresectable advanced medullary thyroid carcinoma (MTC).
  
  
  METHODS
  Sixteen patients with MTC and disease progression or large tumor burden received plitidepsin. Tumor response and time-related parameters were evaluated according to Response Evaluation Criteria in Solid Tumors. Secondary efficacy endpoints were marker response (calcitonin and carcinoembryonic antigen), clinical benefit and quality of life. Safety was assessed using the National Cancer Institute Common Toxicity Criteria.
  
  
  RESULTS
  A total of 141 cycles (median, 9 per patient; range, 1-24) were administered. No complete responses or partial responses (PR) were found, and 12 patients had stable disease for >8 weeks. Median follow-up was 15.0 months. Median time to progression was 5.3 months. Median overall survival could not be calculated, but 86.7% and 66.0% of patients were alive at 6 and 12 months. Marker response included 1 unconfirmed PR and 2 stabilizations for calcitonin, and 1 unconfirmed PR and 4 stabilizations for calcitonin and carcinoembryonic antigen. One patient showed clinical benefit. Quality of life scores generally decreased during the study. Most treatment-related adverse events were mild or moderate. Grade 3 lymphopenia was the only severe hematological toxicity found (2 patients). Severe nonhematological toxicities were grade 3 creatine phosphokinase increase (2 patients, with no myalgia or muscular weakness) and transient grade 3 alanine aminotransferase increase (5 patients).
  
  
  CONCLUSIONS
  Single-agent plitidepsin given as 3-hour i.v. infusions every 2 weeks was generally well tolerated but showed limited clinical activity in patients with unresectable advanced MTC.
authors.affiliation: Department of Nuclear Medicine and Endocrine Oncology, Institut Gustave Roussy, Villejuif, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Baudin
authors.forename: Jean P
authors.initials: JP
authors.lastname: Droz
authors.forename: Luis
authors.initials: L
authors.lastname: Paz-Ares
authors.forename: Allan T
authors.initials: AT
authors.lastname: van Oosterom
authors.forename: Martin
authors.initials: M
authors.lastname: Cullell-Young
authors.forename: Martin
authors.initials: M
authors.lastname: Schlumberger
mesh_terms: D000328:Adult; D000368:Aged; D020295:Brain Stem Neoplasms / Q000188:drug therapy* / Q000556:secondary; D047630:Depsipeptides / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010456:Peptides, Cyclic; D011379:Prognosis; D015996:Survival Rate; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D047630:Depsipeptides; D010456:Peptides, Cyclic; C098980:plitidepsin