title: Gastrazole (JB95008), a novel CCK2/gastrin receptor antagonist, in the treatment of advanced pancreatic cancer: results from two randomised controlled trials.
abstract: Gastrin has been shown to be a growth stimulant in pancreatic cancer cells. Gastrazole is a potent and selective gastrin receptor antagonist. Two randomised blinded trials were conducted to assess the effect of gastrazole in advanced pancreatic cancer. Patients with biopsy-proven, inoperable pancreatic carcinoma were recruited. Trial A compared protracted venous infusion (PVI) gastrazole with PVI placebo, whereas trial B compared PVI gastrazole with PVI fluorouracil (5-FU). Eighteen patients were randomised in trial A. Gastrazole produced significantly better survival compared to placebo (median 7.9 months vs 4.5 months; 1-year survival: 33 vs 11%, respectively; log rank P=0.02). No difference in toxicity was seen between gastrazole and placebo, except central venous catheter and pump complications. Ninety-eight patients were randomised in trial B. No significant survival difference was detected between gastrazole and 5-FU (median: 3.6 vs 4.2 months; 1-year survival: 13.2 vs 26.2%, respectively; log rank P=0.42). Toxicity of gastrazole was mild with significantly less diarrhoea (P=0.03), stomatitis (P<0.001) and hand- foot syndrome (P<0.001) compared to 5-FU. Quality of life (QoL) assessment showed similar QoL between gastrazole and 5-FU at baseline and no significant differences occurred with treatment either between arms or within arms. Compared to placebo, patients with advanced pancreatic cancer treated with gastrazole appeared to live longer, albeit in a very small trial and will require confirmation with large-scale randomised data. However, it did not produce survival advantage over PVI 5-FU. Lack of toxicity for gastrazole may allow its combination with cytotoxic drugs.
authors.affiliation: Department of Medicine, Royal Marsden Hospital, Downs Road, Sutton, Surrey SM2 5PT, and University College London Hospitals, UK.
authors.forename: I
authors.initials: I
authors.lastname: Chau
authors.forename: D
authors.initials: D
authors.lastname: Cunningham
authors.forename: C
authors.initials: C
authors.lastname: Russell
authors.forename: A R
authors.initials: AR
authors.lastname: Norman
authors.forename: T
authors.initials: T
authors.lastname: Kurzawinski
authors.forename: P
authors.initials: P
authors.lastname: Harper
authors.forename: P
authors.initials: P
authors.lastname: Harrison
authors.forename: G
authors.initials: G
authors.lastname: Middleton
authors.forename: F
authors.initials: F
authors.lastname: Daniels
authors.forename: T
authors.initials: T
authors.lastname: Hickish
authors.forename: J
authors.initials: J
authors.lastname: Prendeville
authors.forename: P J
authors.initials: PJ
authors.lastname: Ross
authors.forename: B
authors.initials: B
authors.lastname: Theis
authors.forename: R
authors.initials: R
authors.lastname: Hull
authors.forename: M
authors.initials: M
authors.lastname: Walker
authors.forename: N
authors.initials: N
authors.lastname: Shankley
authors.forename: B
authors.initials: B
authors.lastname: Kalindjian
authors.forename: G
authors.initials: G
authors.lastname: Murray
authors.forename: A
authors.initials: A
authors.lastname: Gillbanks
authors.forename: J
authors.initials: J
authors.lastname: Black
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000627:therapeutic use*; D005500:Follow-Up Studies; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D010865:Pilot Projects; D010919:Placebos; D011237:Predictive Value of Tests; D043887:Receptor, Cholecystokinin B / Q000037:antagonists & inhibitors*; D016037:Single-Blind Method; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D010919:Placebos; D043887:Receptor, Cholecystokinin B; D005472:Fluorouracil