title: A phase II study of isoflavones, erlotinib, and gemcitabine in advanced pancreatic cancer.
abstract: BACKGROUND
  The EGFR/Akt/NF-κB signalling pathway is frequently deregulated in pancreatic cancer and contributes to cell growth, metastasis and chemoresistance. An isoflavone, genistein, inactivates Akt and NF-κB and enhances the anti-tumor activity of erlotinib and gemcitabine in experimental systems of pancreas cancer. This phase II study was undertaken to determine the effects of adding isoflavone to a regimen of gemcitabine and erlotinib on survival in patients with advanced pancreatic cancer.
  
  
  METHODS
  Eligibility included previously untreated patients with advanced pancreatic adenocarcinoma. Patients received gemcitabine 1,000 mg/m² on days 1, 8, and 15, and erlotinib 150 mg once daily P.O. on day 1 to day 28. Soy isoflavones (Novasoy®) were administered at a dose of 531 mg twice daily P.O. starting day -7 until the end of study participation.
  
  
  RESULTS
  Twenty patients with advanced pancreas cancer were enrolled (median age 57.9 years). Sixteen patients had stage IV disease. The median number of cycles was 2 per patient. The median survival time was 5.2 months (95% CI, 4.6-N/A months). The probability of survival at 6 months was 50% (95% CI, 32-78%).
  
  
  CONCLUSIONS
  The addition of soy isoflavones to gemcitabine and erlotinib did not appear to increase the survival of patients with advanced pancreatic cancer.
authors.affiliation: Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA. belraye@emory.edu
authors.forename: Bassel Fuad
authors.initials: BF
authors.lastname: El-Rayes
authors.forename: Philip A
authors.initials: PA
authors.lastname: Philip
authors.forename: Fazlul H
authors.initials: FH
authors.lastname: Sarkar
authors.forename: Anthony F
authors.initials: AF
authors.lastname: Shields
authors.forename: Ann Marie
authors.initials: AM
authors.lastname: Ferris
authors.forename: Kenneth
authors.initials: K
authors.lastname: Hess
authors.forename: Ahmad O
authors.initials: AO
authors.lastname: Kaseb
authors.forename: Milind M
authors.initials: MM
authors.lastname: Javle
authors.forename: Gauri R
authors.initials: GR
authors.lastname: Varadhachary
authors.forename: Robert A
authors.initials: RA
authors.lastname: Wolff
authors.forename: James L
authors.initials: JL
authors.lastname: Abbruzzese
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D000069347:Erlotinib Hydrochloride; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007529:Isoflavones / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000093542:Gemcitabine
chemical_list: D000970:Antineoplastic Agents; D007529:Isoflavones; D016328:NF-kappa B; D011799:Quinazolines; D003841:Deoxycytidine; D000069347:Erlotinib Hydrochloride; D051057:Proto-Oncogene Proteins c-akt; D000093542:Gemcitabine