title: Gemcitabine with a specific conformal 3D 5FU radiochemotherapy technique is safe and effective in the definitive management of locally advanced pancreatic cancer.
abstract: The aim of this phase II study was to assess the feasibility and efficacy of a specific three-dimensional conformal radiotherapy technique with concurrent continuous infusion of 5-fluorouracil (CI 5FU) sandwiched between gemcitabine chemotherapy in patients with locally advanced pancreatic cancer. Patients with inoperable cancer in the pancreatic head or body without metastases were given gemcitabine at 1000 mg m(-2) weekly for 3 weeks followed by a 1-week rest and a 6-week period of radiotherapy and concurrent CI 5FU (200 mg m(-2) day(-1)). The defined target volume was treated to 54 Gy in 30 daily fractions of 1.8 Gy. After 4 weeks' rest, gemcitabine treatment was re-initiated for three cycles (days 1, 8, 15, q28). Forty-one patients were enrolled. At the end of radiotherapy, one patient (2.4%) had a complete response and four patients (9.6%) had a partial response; at the end of treatment, three patients (7.3%) had a complete response and two patients (4.9%) had a partial response. Median survival time was 11.7 months, median time to progression was 7.1 months, and median time to failure of local control was 11.9 months. The 1- and 2-year survival rates were 46.3 and 9.8%, respectively. Treatment-related grade 3 and 4 toxicities were reported by 16 (39.0%) and four (9.8%) patients, respectively. Sixteen out of 41 patients did not complete the planned treatment and nine due to disease progression. This approach to treatment of locally advanced pancreatic cancer is safe and promising, with good local control for a substantial proportion of patients, and merits testing in a randomised trial.
authors.affiliation: Department of Medical Oncology, Prince of Wales Hospital, Barker Street, Randwick, New South Wales 2031, Australia. David.Goldstein@SESIAHS.HEALTH.NSW.GOV.AU
authors.forename: D
authors.initials: D
authors.lastname: Goldstein
authors.forename: G
authors.initials: G
authors.lastname: Van Hazel
authors.forename: E
authors.initials: E
authors.lastname: Walpole
authors.forename: C
authors.initials: C
authors.lastname: Underhill
authors.forename: D
authors.initials: D
authors.lastname: Kotasek
authors.forename: M
authors.initials: M
authors.lastname: Michael
authors.forename: J
authors.initials: J
authors.lastname: Shapiro
authors.forename: T
authors.initials: T
authors.lastname: Davies
authors.forename: W
authors.initials: W
authors.lastname: Reece
authors.forename: J
authors.initials: J
authors.lastname: Harvey
authors.forename: N
authors.initials: N
authors.lastname: Spry
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D000328:Adult; D000368:Aged; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects; D003131:Combined Modality Therapy / Q000009:adverse effects; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D005240:Feasibility Studies; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D021621:Imaging, Three-Dimensional; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D011881:Radiotherapy, Computer-Assisted / Q000009:adverse effects; D020266:Radiotherapy, Conformal / Q000009:adverse effects; D016019:Survival Analysis; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D005472:Fluorouracil; D000093542:Gemcitabine