title: Safety, tolerability, and pharmacokinetics of the anti-IGF-1R monoclonal antibody figitumumab in patients with refractory adrenocortical carcinoma.
abstract: OBJECTIVE
  Insulin-like growth factor 1 receptor signaling through upregulation of the stimulatory ligand IGF-II has been implicated in the pathogenesis of adrenocortical carcinoma. As there is a paucity of effective therapies, this dose expansion cohort of a phase 1 study was undertaken to determine the safety, tolerability, pharmacokinetics, and effects on endocrine markers of figitumumab in patients with adrenocortical carcinoma.
  
  
  METHODS
  Figitumumab was administered on day 1 of each 21-day cycle at the maximal feasible dose (20 mg/kg) to a cohort of patients with metastatic, refractory adrenocortical carcinoma. Serum glucose, insulin, and growth hormone were measured pre-study, at cycle 4 and study end. Pharmacokinetic evaluation was performed during cycles 1 and 4.
  
  
  RESULTS
  Fourteen patients with adrenocortical carcinoma received 50 cycles of figitumumab at the 20 mg/kg. Treatment-related toxicities were generally mild and included hyperglycemia, nausea, fatigue, and anorexia. Single episodes of grade 4 hyperuricemia, proteinuria, and elevated gamma-glutamyltransferase were observed. Pharmacokinetics of figitumumab was comparable to patients with solid tumors other than adrenocortical carcinoma. Treatment with figitumumab increased serum insulin and growth hormone levels. Eight of 14 patients (57%) had stable disease.
  
  
  CONCLUSIONS
  The side effect profile and pharmacokinetics of figitumumab were similar in patients with adrenocortical carcinoma in comparison to patients with other solid tumors. While hyperglycemia was the most common adverse event, no clear patterns predicting severity were observed. The majority of patients receiving protocol therapy with single agent figitumumab experienced stability of disease, warranting further evaluation.
authors: Division of Medical Oncology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA. haluska.paul@mayo.edu
authors: Paul
authors: P
authors: Haluska
authors: Frank
authors: F
authors: Worden
authors: David
authors: D
authors: Olmos
authors: Donghua
authors: D
authors: Yin
authors: David
authors: D
authors: Schteingart
authors: Gretchen N
authors: GN
authors: Batzel
authors: M Luisa
authors: ML
authors: Paccagnella
authors: Johann S
authors: JS
authors: de Bono
authors: Antonio
authors: A
authors: Gualberto
authors: Gary D
authors: GD
authors: Hammer
mesh_terms: D000306:Adrenal Cortex Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D018268:Adrenocortical Carcinoma / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D000328:Adult; D000368:Aged; D000855:Anorexia / Q000139:chemically induced; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D019540:Area Under Curve; D015331:Cohort Studies; D004334:Drug Administration Schedule; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D013006:Growth Hormone / Q000097:blood; D006801:Humans; D006943:Hyperglycemia / Q000139:chemically induced; D016756:Immunoglobulins, Intravenous; D007262:Infusions, Intravenous; D007328:Insulin / Q000097:blood; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors* / Q000276:immunology; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D016756:Immunoglobulins, Intravenous; D007328:Insulin; D013006:Growth Hormone; D017526:Receptor, IGF Type 1; C525021:figitumumab