title: Chemo-radiotherapy for localized pancreatic cancer: increased dose intensity and reduced acute toxicity with concomitant radiotherapy and protracted venous infusion 5-fluorouracil.
abstract: OBJECTIVE
  Although concomitant radiation therapy (RT) and bolus 5-Fluorouracil (5-FU) have been shown to improve survival in locally confined pancreatic cancer, most patients will eventually succumb to their disease. Since 1994, we have attempted to improve efficacy by administering 5-FU as a protracted venous infusion (PVI). This study compares treatment intensity and acute toxicity of consecutive protocols of concurrent RT and 5-FU by bolus injection or PVI.
  
  
  METHODS
  Since 1986, 74 patients with resected or locally advanced pancreatic cancer were treated with continuous course RT and concurrent 5-FU by bolus injection (n = 44) or PVI throughout the course of RT (n = 30). Dose intensity was assessed for both 5-FU and radiotherapy. Toxicity endpoints which could be reliably and objectively quantified (e.g., neutropenia, weight loss, treatment interruption) were evaluated.
  
  
  RESULTS
  Cumulative 5-FU dose (mean = 7.2 vs. 2.5 gm/m2, p < 0.001) and weekly 5-FU dose (mean = 1.3 vs. 0.5 gm/m2/wk, p < 0.001) were significantly higher for patients receiving PVI 5-FU. Following pancreaticoduodenectomy, 95% of PVI patients maintained a RT dose intensity of > or = 900 cGy/wk, compared with 63% of those receiving bolus 5-FU (p = 0.02). No difference was seen for patients with locally advanced disease (72% vs. 76%, p = n.s.). Grade II-III neutropenia was less common for patients treated with PVI (13% vs. 34%, p = 0.05). Grade II-III thrombocytopenia was uncommon (< or = 3%) in both treatment groups. Mean percent weight loss (3.8% vs. 4.1%, p = n.s.) and weight loss > or = 5% of pre-treatment weight (21% vs. 31%, p = n.s.) were similar for PVI and bolus treatment groups, respectively. Treatment interruptions for hematologic, gastrointestinal or other acute toxicities were less common for patients receiving PVI 5-FU (10% vs. 25%, p = 0.11).
  
  
  CONCLUSIONS
  Concurrent RT and 5-FU by PVI was well tolerated and permitted greater chemotherapy and radiotherapy dose intensity with reduced hematologic toxicity and fewer treatment interruptions compared with RT and bolus 5-FU. Longer follow-up will be needed to assess late effects and the impact on overall survival.
authors.affiliation: Department of Radiation Oncology, Stanford University, CA 94305, USA. poen@reyes.stanford.edu
authors.forename: J C
authors.initials: JC
authors.lastname: Poen
authors.forename: H L
authors.initials: HL
authors.lastname: Collins
authors.forename: J E
authors.initials: JE
authors.lastname: Niederhuber
authors.forename: H A
authors.initials: HA
authors.lastname: Oberhelman
authors.forename: M A
authors.initials: MA
authors.lastname: Vierra
authors.forename: A J
authors.initials: AJ
authors.lastname: Bastidas
authors.forename: H S
authors.initials: HS
authors.lastname: Young
authors.forename: E A
authors.initials: EA
authors.lastname: Slosberg
authors.forename: B R
authors.initials: BR
authors.lastname: Jeffrey
authors.forename: T A
authors.initials: TA
authors.lastname: Longacre
authors.forename: G A
authors.initials: GA
authors.lastname: Fisher
authors.forename: D R
authors.initials: DR
authors.lastname: Goffinet
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D003131:Combined Modality Therapy; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D011879:Radiotherapy Dosage
chemical_list: D000964:Antimetabolites, Antineoplastic; D005472:Fluorouracil