title: Induction chemotherapy with gemcitabine, oxaliplatin, and 5-fluorouracil/leucovorin followed by concomitant chemoradiotherapy in patients with locally advanced pancreatic cancer: a Taiwan cooperative oncology group phase II study.
abstract: OBJECTIVE
  To evaluate the therapeutic efficacy of 3-month triplet induction chemotherapy (ICT) followed by concomitant chemoradiotherapy (CCRT) in patients with locally advanced pancreatic cancer (LAPC).
  
  
  METHODS
  Chemonaïve patients with measurable, histologically confirmed LAPC were eligible. The ICT consisted of biweekly gemcitabine (800 mg/m2) infusion at a fixed dose rate (10 mg/m2/min), followed by 85 mg/m2 oxaliplatin and 48-h infusion of 5-fluorouracil/leucovorin (3000/150 mg/m2) for 6 cycles. Patients without disease progression 4 weeks after ICT would receive weekly 400 mg/m2 gemcitabine and 5040 cGy radiation in 28 fractions. After CCRT, patients were subjected for surgical intervention and/or maintenance chemotherapy until progression or intolerable toxicity.
  
  
  RESULTS
  Between December 2004 and August 2008, 50 patients were enrolled. The best responses after ICT were partial response (PR) in 9, stable disease in 26, and progressive disease or not evaluable in 15. Among the former 35 patients, 2 had disease progression before CCRT, and 3 declined to have CCRT. Of the 30 patients receiving CCRT, an additional 4 and 1 patient(s) achieved PR at the end of CCRT and during maintenance chemotherapy, respectively. On intent-to-treat analysis, the overall best response was PR in 14 patients and stable disease in 21. The overall response rate and disease control rate were 28% (95% confidence interval [CI], 16.2-42.5%) and 70% (95% CI, 44.4-99.2%), respectively. The median time to progression and overall survival of the intent-to-treat population was 9.3 (95% CI, 5.8-12.8) months and 14.5 (95% CI, 11.9-17.1) months, respectively. One- and two-year survival rates were 68% (95% CI, 55.1-80.9%) and 20.6% (95% CI, 8.7-32.5%), respectively. Neutropenia was the most common Grade 3-4 toxicity of both ICT and CCRT, with a frequency of 28% and 26.7%, respectively. Significant sensory neuropathy occurred in 9 patients (18%).
  
  
  CONCLUSIONS
  Three months of triplet ICT followed by gemcitabine-based CCRT is feasible, moderately active, and associated with encouraging survival in patients with LAPC.
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, Miaoli, Taiwan.
authors.forename: Hui-Ju
authors.initials: HJ
authors.lastname: Ch'ang
authors.forename: Yu-Lin
authors.initials: YL
authors.lastname: Lin
authors.forename: Hsiu-Po
authors.initials: HP
authors.lastname: Wang
authors.forename: Yen-Feng
authors.initials: YF
authors.lastname: Chiu
authors.forename: Ming-Chu
authors.initials: MC
authors.lastname: Chang
authors.forename: Chih-Hung
authors.initials: CH
authors.lastname: Hsu
authors.forename: Yu-Wen
authors.initials: YW
authors.lastname: Tien
authors.forename: Jen-Shi
authors.initials: JS
authors.lastname: Chen
authors.forename: Ruey-Kuen
authors.initials: RK
authors.lastname: Hsieh
authors.forename: Pin-Wen
authors.initials: PW
authors.lastname: Lin
authors.forename: Yan-Shen
authors.initials: YS
authors.lastname: Shan
authors.forename: Ann-Lii
authors.initials: AL
authors.lastname: Cheng
authors.forename: Jang-Yang
authors.initials: JY
authors.lastname: Chang
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Whang-Peng
authors.forename: Tsann-Long
authors.initials: TL
authors.lastname: Hwang
authors.forename: Li-Tzong
authors.initials: LT
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D059248:Chemoradiotherapy / Q000009:adverse effects / Q000379:methods*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018450:Disease Progression; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D060828:Induction Chemotherapy / Q000379:methods*; D002955:Leucovorin / Q000008:administration & dosage; D060046:Maintenance Chemotherapy; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000209:etiology; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D011446:Prospective Studies; D011879:Radiotherapy Dosage; D020266:Radiotherapy, Conformal / Q000009:adverse effects; D015996:Survival Rate; D013624:Taiwan; D000093542:Gemcitabine
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D002955:Leucovorin; D005472:Fluorouracil; D000093542:Gemcitabine