title: A phase II clinical study of mFOLFOX6 plus bevacizumab as first-line therapy for Japanese advanced/recurrent colorectal cancer patients.
abstract: OBJECTIVE
  In Japan, there had been no prospective clinical studies conducted in terms of modified FOLFOX6 + bevacizumab therapy. We performed a post-marketing Phase II multicenter clinical study to examine the efficacy and safety of this regimen as first-line therapy for Japanese patients with advanced/recurrent colorectal cancer.
  
  
  METHODS
  Bevacizumab (5 mg/kg) was administered intravenously, and then oxaliplatin (85 mg/m(2)) and levofolinate calcium (200 mg/m(2)) were infused intravenously over 2 h. Subsequently, a bolus dose of 5-fluorouracil (400 mg/m(2)) was injected, followed by infusion of 5-fluorouracil (2400 mg/m(2)) for 46 h. This regimen was repeated every 2 weeks until 24 cycles unless there was disease progression, unacceptable toxicity or patient refusal. The primary end point was the response rate.
  
  
  RESULTS
  Among the 70 patients enrolled, two patients withdrew the study before treatment, and 68 patients were eligible for analysis of efficacy and safety. The response rate was 51.5% (95% confidence interval: 39.0-63.8%). The median progression-free survival and median overall survival time were 12.6 months (95% confidence interval: 10.4-14.5 months) and 28.5 months [95% confidence interval: 23.1 months-(not applicable)], respectively. There were no treatment-related deaths observed. The most common Grade 3 and 4 adverse events included neutropenia in 35.3% of the patients, peripheral neuropathy in 16.2% and hypertension in 16.2%. All adverse events were manageable and tolerable. The exploratory analysis of polymorphisms of three genes, ERCC1, XPD and GSTP1, did not show any trends in terms of correlation with the efficacy or safety of modified FOLFOX6 + bevacizumab therapy.
  
  
  CONCLUSIONS
  Modified FOLFOX6 + bevacizumab therapy was manageable and tolerable in Japanese patients, achieving a high response rate.
authors.affiliation: *National Hospital Organization Shikoku Cancer Center, Kou 160 Minamiumemotomachi, Matsuyama, Ehime 791-0280, Japan. tnishina@shikoku-cc.go.jp.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Nishina
authors.forename: Yoshinao
authors.initials: Y
authors.lastname: Takano
authors.forename: Tadamichi
authors.initials: T
authors.lastname: Denda
authors.forename: Hisateru
authors.initials: H
authors.lastname: Yasui
authors.forename: Koji
authors.initials: K
authors.lastname: Takeda
authors.forename: Takashi
authors.initials: T
authors.lastname: Ura
authors.forename: Taito
authors.initials: T
authors.lastname: Esaki
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Okuyama
authors.forename: Ken
authors.initials: K
authors.lastname: Kondo
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Sugiyama
authors.forename: Kei
authors.initials: K
authors.lastname: Muro
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D044466:Asian People / Q000706:statistics & numerical data; D000068258:Bevacizumab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D004268:DNA-Binding Proteins / Q000235:genetics; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D004720:Endonucleases / Q000235:genetics; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D005500:Follow-Up Studies; D005838:Genotype; D051549:Glutathione S-Transferase pi / Q000235:genetics; D006801:Humans; D007262:Infusions, Intravenous; D007564:Japan / Q000453:epidemiology; D053208:Kaplan-Meier Estimate; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D060888:Real-Time Polymerase Chain Reaction; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D004268:DNA-Binding Proteins; D009944:Organoplatinum Compounds; D000068258:Bevacizumab; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; C071447:ERCC1 protein, human; D004720:Endonucleases; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human; D002955:Leucovorin; D005472:Fluorouracil
keywords: FOLFOX; bevacizumab; colorectal cancer