title: Addition of vandetanib to pegylated liposomal doxorubicin (PLD) in patients with recurrent ovarian cancer. A randomized phase I/II study of the AGO Study Group (AGO-OVAR 2.13).
abstract: BACKGROUND
  PLD is a standard treatment in patients with recurrent platinum-resistant or refractory ovarian cancer. Vandetanib is an oral once daily administered inhibitor of VEGFR-, EGFR- and RET-signaling with activity in combination with chemotherapy in some solid tumours. We aimed to establish a feasible combination therapy of PLD and vandetanib in ovarian cancer.
  
  
  METHODS
  Eligible patients were treated with PLD 50 mg/m(2) q28 and vandetanib 100 mg/d po. It was planned to recruit at least 10 patients evaluable for toxicity over 2 treatment cycles. Primary endpoints were tolerability and safety; secondary endpoint was efficacy.
  
  
  RESULTS
  Fourteen of 15 registered patients started treatment and were evaluable for toxicity. Three patients (21%) stopped after first cycle (PD, withdrawal of consent, nausea/vomiting). The remaining 11 patients were treated for at least 2 cycles. Dose reductions of PLD and vandetanib were indicated in 4 (29%) and 5 patients (36%), respectively. The following G3/4 toxicities occurred per patient: 2 (14%) elevated liver enzymes G3, 2 (14%) neutropenia G3/4, 5 (36%) PPE G3/4, 2 (14%) mucositis G3. Tyrosine kinase inhibitor attributed side effects like hypertension or bowel perforations were not reported. Toxicity led to cessation of treatment in 4 patients (29%). Ten patients were evaluable for response: PR 1, SD 4. The median PFS was 6.7 months and median OS was 11.1 months.
  
  
  CONCLUSIONS
  The combination of PLD 50 mg/m(2)q28 and vandetanib 100 mg/d is feasible, but may be intolerable due to reported toxicity.
authors.affiliation: Department of Gynecology and Gynecologic Oncology, Kliniken Essen-Mitte, Henricistr. 92, 45136, Essen, Germany, p.harter@gmx.de.
authors.forename: Philipp
authors.initials: P
authors.lastname: Harter
authors.forename: Jalid
authors.initials: J
authors.lastname: Sehouli
authors.forename: Rainer
authors.initials: R
authors.lastname: Kimmig
authors.forename: Jörn
authors.initials: J
authors.lastname: Rau
authors.forename: Felix
authors.initials: F
authors.lastname: Hilpert
authors.forename: Christian
authors.initials: C
authors.lastname: Kurzeder
authors.forename: Gabriele
authors.initials: G
authors.lastname: Elser
authors.forename: Andreas
authors.initials: A
authors.lastname: du Bois
mesh_terms: D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D010880:Piperidines / Q000008:administration & dosage; D011092:Polyethylene Glycols / Q000008:administration & dosage; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage; D011799:Quinazolines / Q000008:administration & dosage; D012871:Skin Diseases / Q000139:chemically induced
chemical_list: D000903:Antibiotics, Antineoplastic; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D004317:Doxorubicin; C452423:vandetanib