CONTEXT: Prostate cancer patients at increased risk for relapse after prostatectomy were treated in a neoadjuvant study with androgen deprivation therapy (ADT) in combination with cixutumumab, an inhibitory fully human monoclonal antibody against IGF receptor 1 (IGF-IR). OBJECTIVE: A clinical trial with prospective collection of serum and tissue was designed to test the potential clinical efficacy of neoadjuvant IGF-IR blockade combined with ADT in these patients. The effect of body mass index (BMI) on response of IGF-IR/insulin components to IGF-IR blockade was also examined. DESIGN: Eligibility for the trial required the presence of high-risk prostate adenocarcinoma. Treatment consisted of bicalutamide, goserelin, and cixutumumab for 13 weeks before prostatectomy. Here we report on an analysis of serum samples from 29 enrolled patients. Changes in IGF and glucose homeostasis pathways were compared to control samples from patients in a concurrent clinical trial of neoadjuvant ADT alone. RESULTS: Significant increases were seen in GH (P = .001), IGF-I (P < .0001), IGF-II (P = .003), IGF binding protein (IGFBP)-3 (P < .0001), C-peptide (P = .0038), and insulin (P = .05) compared to patients treated with ADT alone. IGFBP-1 levels were significantly lower in the cixutumumab plus ADT cohort (P = .001). No significant changes in blood glucose were evident. Patients with BMIs in the normal range had significantly higher GH (P < .05) and IGFBP-1 (P < 0.5) levels compared to overweight and obese patients. CONCLUSIONS: Patients with IGF-IR blockade in combination with ADT demonstrated significant changes in IGF and glucose homeostasis pathway factors compared to patients receiving ADT alone. In the patients receiving combination therapy, patients with normal BMI had serum levels of glucose homeostasis components similar to individuals in the ADT-alone cohort, whereas patients with overweight and obese BMIs had serum levels that differed from the ADT cohort.
CONTEXT: Prostate cancerpatients at increased risk for relapse after prostatectomy were treated in a neoadjuvant study with androgen deprivation therapy (ADT) in combination with cixutumumab, an inhibitory fully human monoclonal antibody against IGF receptor 1 (IGF-IR). OBJECTIVE: A clinical trial with prospective collection of serum and tissue was designed to test the potential clinical efficacy of neoadjuvant IGF-IR blockade combined with ADT in these patients. The effect of body mass index (BMI) on response of IGF-IR/insulin components to IGF-IR blockade was also examined. DESIGN: Eligibility for the trial required the presence of high-risk prostate adenocarcinoma. Treatment consisted of bicalutamide, goserelin, and cixutumumab for 13 weeks before prostatectomy. Here we report on an analysis of serum samples from 29 enrolled patients. Changes in IGF and glucose homeostasis pathways were compared to control samples from patients in a concurrent clinical trial of neoadjuvant ADT alone. RESULTS: Significant increases were seen in GH (P = .001), IGF-I (P < .0001), IGF-II (P = .003), IGF binding protein (IGFBP)-3 (P < .0001), C-peptide (P = .0038), and insulin (P = .05) compared to patients treated with ADT alone. IGFBP-1 levels were significantly lower in the cixutumumab plus ADT cohort (P = .001). No significant changes in blood glucose were evident. Patients with BMIs in the normal range had significantly higher GH (P < .05) and IGFBP-1 (P < 0.5) levels compared to overweight and obesepatients. CONCLUSIONS:Patients with IGF-IR blockade in combination with ADT demonstrated significant changes in IGF and glucose homeostasis pathway factors compared to patients receiving ADT alone. In the patients receiving combination therapy, patients with normal BMI had serum levels of glucose homeostasis components similar to individuals in the ADT-alone cohort, whereas patients with overweight and obese BMIs had serum levels that differed from the ADT cohort.
Authors: Jennifer D Wu; Kathy Haugk; Ilsa Coleman; Lillie Woodke; Robert Vessella; Peter Nelson; R Bruce Montgomery; Dale L Ludwig; Stephen R Plymate Journal: Clin Cancer Res Date: 2006-10-15 Impact factor: 12.531
Authors: Jennifer D Wu; Austin Odman; Lily M Higgins; Kathy Haugk; Robert Vessella; Dale L Ludwig; Stephen R Plymate Journal: Clin Cancer Res Date: 2005-04-15 Impact factor: 12.531
Authors: Mark S Soloway; Kapil Pareek; Rooholiah Sharifi; Zev Wajsman; David McLeod; David P Wood; Antonio Puras-Baez Journal: J Urol Date: 2002-01 Impact factor: 7.450
Authors: S L Goldenberg; L H Klotz; J Srigley; M A Jewett; D Mador; Y Fradet; J Barkin; J Chin; J M Paquin; M J Bullock; S Laplante Journal: J Urol Date: 1996-09 Impact factor: 7.450
Authors: Stephen R Plymate; Kathy Haugk; Ilsa Coleman; Lillie Woodke; Robert Vessella; Peter Nelson; R Bruce Montgomery; Dale L Ludwig; Jennifer D Wu Journal: Clin Cancer Res Date: 2007-11-01 Impact factor: 12.531
Authors: Charlie D Chen; Derek S Welsbie; Chris Tran; Sung Hee Baek; Randy Chen; Robert Vessella; Michael G Rosenfeld; Charles L Sawyers Journal: Nat Med Date: 2003-12-21 Impact factor: 53.440
Authors: Evan Y Yu; Hongli Li; Celestia S Higano; Neeraj Agarwal; Sumanta K Pal; Ajjai Alva; Elisabeth I Heath; Elaine T Lam; Shilpa Gupta; Michael B Lilly; Yoshio Inoue; Kim N Chi; Nicholas J Vogelzang; David I Quinn; Heather H Cheng; Stephen R Plymate; Maha Hussain; Catherine M Tangen; Ian M Thompson Journal: J Clin Oncol Date: 2015-04-06 Impact factor: 44.544
Authors: Cale D Fahrenholtz; Ferenc G Rick; Maria I Garcia; Marta Zarandi; Ren-Zhi Cai; Norman L Block; Andrew V Schally; Kerry L Burnstein Journal: Proc Natl Acad Sci U S A Date: 2014-01-06 Impact factor: 11.205
Authors: Caterina Mancarella; Irene Casanova-Salas; Ana Calatrava; Selena Ventura; Cecilia Garofalo; José Rubio-Briones; Vera Magistroni; Maria Cristina Manara; José Antonio López-Guerrero; Katia Scotlandi Journal: Oncotarget Date: 2015-06-30