title: The insulin-like growth factor-I receptor inhibitor figitumumab (CP-751,871) in combination with docetaxel in patients with advanced solid tumours: results of a phase Ib dose-escalation, open-label study.
abstract: BACKGROUND
  This phase Ib trial assessed safety, tolerability, and maximum tolerated dose (MTD) of figitumumab (CP-751,871), a fully human monoclonal antibody targeting the insulin-like growth factor type 1 receptor (IGF-IR), in combination with docetaxel.
  
  
  METHODS
  Patients with advanced solid tumours were treated with escalating dose levels of figitumumab plus 75 mg m(-2) docetaxel every 21 days. Safety, efficacy, pharmacokinetics (PKs), and biomarker responses were evaluated.
  
  
  RESULTS
  In 46 patients, no dose-limiting toxicities were attributable to the treatment combination. Grade 3 and 4 toxicities included neutropaenia (n=28), febrile neutropaenia (n=11), fatigue (n=10), leukopaenia (n=7), diarrhoea (n=5), hyperglycaemia, lymphopaenia, cellulitis, DVT, and pain (all n=1). The MTD was not reached. Four partial responses were observed; 12 patients had disease stabilisation of > or =6 months. Pharmacokinetic and biomarker analyses showed a dose-dependent increase in plasma exposure, and complete sIGF-IR downregulation at doses of >or =3 mg kg(-1). Pharmacokinetics of docetaxel in combination was similar to when given alone. Out of 18 castration-resistant prostate cancer patients, 10 (56%) had > or =5 circulating tumour cells (CTCs) per 7.5 ml of blood at baseline: 6 out of 10 (60%) had a decline from > or =5 to <5 CTCs and 9 out of 10 (90%) had a > or =30% decline in CTCs after therapy.
  
  
  CONCLUSIONS
  Figitumumab and docetaxel in combination are well tolerated. Further evaluation is warranted.
authors.affiliation: The Royal Marsden NHS Foundation Trust/The Institute of Cancer Research, Sutton, Surrey, UK.
authors.forename: L R
authors.initials: LR
authors.lastname: Molife
authors.forename: P C
authors.initials: PC
authors.lastname: Fong
authors.forename: L
authors.initials: L
authors.lastname: Paccagnella
authors.forename: A H M
authors.initials: AH
authors.lastname: Reid
authors.forename: H M
authors.initials: HM
authors.lastname: Shaw
authors.forename: L
authors.initials: L
authors.lastname: Vidal
authors.forename: H-T
authors.initials: HT
authors.lastname: Arkenau
authors.forename: V
authors.initials: V
authors.lastname: Karavasilis
authors.forename: T A
authors.initials: TA
authors.lastname: Yap
authors.forename: D
authors.initials: D
authors.lastname: Olmos
authors.forename: J
authors.initials: J
authors.lastname: Spicer
authors.forename: S
authors.initials: S
authors.lastname: Postel-Vinay
authors.forename: D
authors.initials: D
authors.lastname: Yin
authors.forename: A
authors.initials: A
authors.lastname: Lipton
authors.forename: L
authors.initials: L
authors.lastname: Demers
authors.forename: K
authors.initials: K
authors.lastname: Leitzel
authors.forename: A
authors.initials: A
authors.lastname: Gualberto
authors.forename: J S
authors.initials: JS
authors.lastname: de Bono
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use / Q000633:toxicity*; D000970:Antineoplastic Agents / Q000627:therapeutic use / Q000633:toxicity; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use / Q000633:toxicity; D002481:Cellulitis / Q000139:chemically induced; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D016756:Immunoglobulins, Intravenous; D008231:Lymphopenia / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D009503:Neutropenia / Q000139:chemically induced; D011471:Prostatic Neoplasms / Q000188:drug therapy; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors; D043823:Taxoids / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D016756:Immunoglobulins, Intravenous; D043823:Taxoids; D000077143:Docetaxel; D017526:Receptor, IGF Type 1; C525021:figitumumab