title: Phase II study of gemcitabine plus 5-fluorouracil biologically modulated by folinic acid plus long-acting formulation of octreotide (LAR) in patients with advanced pancreatic cancer.
abstract: OBJECTIVE
  To investigate the efficacy and toxicity of gemcitabine, in combination with 5-fluorouracil (5-FU) biologically modulated by folinic acid (FA) plus a somatostatin analogue (octreotide acetate-long acting formulation-LAR) that can both inhibit the action of several growth factors and angiogenesis, in patients with advanced pancreatic cancer.
  
  
  METHODS
  Thirty-two patients with advanced symptomatic pancreatic cancer with measurable disease and median age 64 years (range 50-72) received the following combination: 5-FU, given at 350 mg/m(2) i.v. bolus, biologically modulated by FA 350 mg/m(2) on days 1, 2, 8 and 9; and gemcitabine, given by short i.v. infusion at 1000 mg/m(2) on days 1 and 8. The regimen was administered every 3 weeks. LAR 30 mg was given intramuscularly every 4 weeks.
  
  
  RESULTS
  Objective tumor response was documented in 7 out of 32 evaluable patients (all partial responses-PR), yielding a 22% response rate (RR) (95% CI 10.5-35). Sixteen (50%) patients (95% CI 31.4-60.8) remained with stable disease (SD), while 9 (28%) patients (95% CI 20.4-48.4) progressed while on chemotherapy. The median response duration (RD) was 7 months (range 4-18). The median time to tumor progression (TTP) was 7 months (range 2-20), while the median survival was 7 months (range 4-29). The probability of surviving beyond 12 months was 20%. Of the 32 patients with tumor-related symptoms who were considered evaluable for clinical benefit response, 25 (78%) had pain improvement, while 14 (44%) experienced weight gain during treatment. In general, performance status improved in 16 (50%) patients during treatment. Serum concentrations of Ca 19-9 were decreased by more than 50% in 14 (44%) of the 32 assessable patients. Chemotherapy was well tolerated with mild myelotoxicity. Gastrointestinal toxicity was moderate with mild mucositis.
  
  
  CONCLUSIONS
  The combination of gemcitabine and 5-FU/FA plus LAR 30 was well tolerated and showed a moderate antitumor activity and a significant palliative effect on tumor-related symptoms. It would be interesting to evaluate in a randomized study the impact of octreotide administration on the palliative effect of the regimen.
authors.affiliation: Medical Oncology Unit, "Laikon" General Hospital, Athens University School of Medicine, Athens, Greece.
authors.forename: A
authors.initials: A
authors.lastname: Polyzos
authors.forename: N
authors.initials: N
authors.lastname: Tsavaris
authors.forename: I
authors.initials: I
authors.lastname: Vafiadis
authors.forename: K
authors.initials: K
authors.lastname: Polyzos
authors.forename: J
authors.initials: J
authors.lastname: Griniatsos
authors.forename: E
authors.initials: E
authors.lastname: Felekouras
authors.forename: N I
authors.initials: NI
authors.lastname: Nikiteas
authors.forename: S
authors.initials: S
authors.lastname: Halikias
authors.forename: G
authors.initials: G
authors.lastname: Nikou