title: Phase II study of safety and efficacy of motesanib in patients with progressive or symptomatic, advanced or metastatic medullary thyroid cancer.
abstract: OBJECTIVE
  This phase II study investigated the efficacy and tolerability of motesanib, an investigational, highly selective inhibitor of vascular endothelial growth factor receptors 1, 2, and 3; platelet-derived growth factor receptor; and Kit in advanced medullary thyroid cancer (MTC).
  
  
  METHODS
  Patients with locally advanced or metastatic, progressive or symptomatic MTC received motesanib 125 mg/d orally for up to 48 weeks or until unacceptable toxicity or disease progression. The primary end point was objective response by independent review. Other end points included duration of response, progression-free survival, safety, pharmacokinetics, and changes in tumor markers.
  
  
  RESULTS
  Of 91 enrolled patients who received motesanib, two (2%) achieved objective response (95% CI, 0.3% to 7.7%); their duration of response was 32 weeks (censored) and 21 weeks (disease progressed). Eighty-one percent of patients had stable disease (48% had durable stable disease > or = 24 weeks), 8% had disease progression as best response, and 9% were not evaluated; 76% experienced a decrease from baseline in target lesion measurement. Median progression-free survival was 48 weeks (95% CI, 43 to 56 weeks). Among patients with tumor marker analysis, 69 (83%) of 83 and 63 (75%) of 84 had decreased serum calcitonin and carcinoembryonic antigen during treatment, respectively, compared with baseline. The most common treatment-related adverse events were diarrhea (41%), fatigue (41%), hypothyroidism (29%), hypertension (27%), and anorexia (27%). In pharmacokinetic analyses, motesanib trough concentrations were lower compared with differentiated thyroid cancer patients from the same study.
  
  
  CONCLUSIONS
  Although the objective response rate was low, a significant proportion of MTC patients (81%) achieved stable disease while receiving motesanib.
authors: Institut Gustave Roussy, rue Camille Desmoulins, 94805 Villejuif Cédex, France. martin.schlumberger@igr.fr
authors: Martin J
authors: MJ
authors: Schlumberger
authors: Rossella
authors: R
authors: Elisei
authors: Lars
authors: L
authors: Bastholt
authors: Lori J
authors: LJ
authors: Wirth
authors: Renato G
authors: RG
authors: Martins
authors: Laura D
authors: LD
authors: Locati
authors: Barbara
authors: B
authors: Jarzab
authors: Furio
authors: F
authors: Pacini
authors: Chantal
authors: C
authors: Daumerie
authors: Jean-Pierre
authors: JP
authors: Droz
authors: Michael J
authors: MJ
authors: Eschenberg
authors: Yu-Nien
authors: YN
authors: Sun
authors: Todd
authors: T
authors: Juan
authors: Daniel E
authors: DE
authors: Stepan
authors: Steven I
authors: SI
authors: Sherman
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D018276:Carcinoma, Medullary / Q000188:drug therapy* / Q000473:pathology*; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D009841:Oligonucleotides; D019009:Proto-Oncogene Proteins c-kit / Q000187:drug effects; D017479:Receptors, Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D009841:Oligonucleotides; D009536:Niacinamide; D019009:Proto-Oncogene Proteins c-kit; D017479:Receptors, Platelet-Derived Growth Factor; D040262:Receptors, Vascular Endothelial Growth Factor; C519562:imetelstat