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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 ¼ 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 ¼ 0.42). Toxicity of gastrazole was mild with significantly less diarrhoea (P ¼ 0.03), stomatitis (Po0.001) and hand -foot syndrome (Po0.001) 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.

ObjectiveIn patients who have undergone a potentially curative resection of colorectal cancer, does a ‘second-look’ operation to resect recurrence, prompted by monthly monitoring of carcinoembryonic antigen, confer a survival benefit?DesignA randomised controlled trial recruiting patients from 1982 to 1993 was recovered under the Restoring Invisible and Abandoned Trials (RIAT) initiative.Setting58 hospitals in the UK.ParticipantsFrom 1982 to 1993, 1447 patients were enrolled. Of these 216 met the criteria for carcinoembryonic antigen (CEA) elevation and were randomised to ‘Aggressive’ or ‘Conventional’ arms.Interventions‘Second-look’ surgery with intention to remove any recurrence discovered.Primary outcome measureSurvival.ResultsBy February 1993, 91/108 patients had died in the ‘Aggressive arm’ and 88/108 in the ‘Conventional’ arm (relative risk=1.16, 95% CI 0.87 to 1.37). By 2011 a further 25 randomised patients had died. Kaplan-Meier analysis showed no difference in long-term survival.ConclusionsThe trial was closed in 1993 following a recommendation from the Data Monitoring Committee that it was highly unlikely that any survival advantage would be demonstrated for CEA prompted second-look surgery. This conclusion was confirmed by repeat analysis of survival times after 20 years.Trial registration numberISRCTN76694943.

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