• Adjuvant chemotherapy with fluorouracil plus folinic acid vs gemcitabine following pancreatic cancer resection: a randomized controlled trial.

      Neoptolemos, John P; Stocken, Deborah D; Bassi, Claudio; Ghaneh, Paula; Cunningham, David; Goldstein, David; Padbury, Robert; Moore, Malcolm J; Gallinger, Steven; Mariette, Christophe; et al. (2010-09-08)
      CONTEXT: Adjuvant fluorouracil has been shown to be of benefit for patients with resected pancreatic cancer. Gemcitabine is known to be the most effective agent in advanced disease as well as an effective agent in patients with resected pancreatic cancer. OBJECTIVE: To determine whether fluorouracil or gemcitabine is superior in terms of overall survival as adjuvant treatment following resection of pancreatic cancer. DESIGN, SETTING, AND PATIENTS: The European Study Group for Pancreatic Cancer (ESPAC)-3 trial, an open-label, phase 3, randomized controlled trial conducted in 159 pancreatic cancer centers in Europe, Australasia, Japan, and Canada. Included in ESPAC-3 version 2 were 1088 patients with pancreatic ductal adenocarcinoma who had undergone cancer resection; patients were randomized between July 2000 and January 2007 and underwent at least 2 years of follow-up. INTERVENTIONS: Patients received either fluorouracil plus folinic acid (folinic acid, 20 mg/m(2), intravenous bolus injection, followed by fluorouracil, 425 mg/m(2) intravenous bolus injection given 1-5 days every 28 days) (n = 551) or gemcitabine (1000 mg/m(2) intravenous infusion once a week for 3 of every 4 weeks) (n = 537) for 6 months. MAIN OUTCOME MEASURES: Primary outcome measure was overall survival; secondary measures were toxicity, progression-free survival, and quality of life. RESULTS: Final analysis was carried out on an intention-to-treat basis after a median of 34.2 (interquartile range, 27.1-43.4) months' follow-up after 753 deaths (69%). Median survival was 23.0 (95% confidence interval [CI], 21.1-25.0) months for patients treated with fluorouracil plus folinic acid and 23.6 (95% CI, 21.4-26.4) months for those treated with gemcitabine (chi(1)(2) = 0.7; P = .39; hazard ratio, 0.94 [95% CI, 0.81-1.08]). Seventy-seven patients (14%) receiving fluorouracil plus folinic acid had 97 treatment-related serious adverse events, compared with 40 patients (7.5%) receiving gemcitabine, who had 52 events (P < .001). There were no significant differences in either progression-free survival or global quality-of-life scores between the treatment groups. CONCLUSION: Compared with the use of fluorouracil plus folinic acid, gemcitabine did not result in improved overall survival in patients with completely resected pancreatic cancer. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00058201.
    • Alternating irinotecan with oxaliplatin combined with UFT plus leucovorin (SCOUT) in metastatic colorectal cancer.

      Sheikh, Hamid Y; Valle, Juan W; Waddell, Thomas K; Palmer, Karen; Wilson, Gregory; Sjursen, Ann-Marie; Craven, Olive; Swindell, Ric; Saunders, Mark P; Department of Clinical Oncology, Christie Hospital, Manchester, UK. (2008-08-19)
      Tegafur-uracil (UFT) plus leucovorin (LV, folinic acid) with alternating irinotecan and oxaliplatin were effective and well tolerated in patients with metastatic colorectal cancer (mCRC) in a phase I study. This study expanded the maximum tolerated dose group. Patients aged >or=18 years had histologically confirmed, inoperable, previously untreated, measurable mCRC. Patients received irinotecan 180 mg m(-2) on day 1, oxaliplatin 100 mg m(-2) on day 15 and UFT 250 mg m(-2) plus LV 90 mg on days 1-21 every 28 days. The phase I/II study comprised 45 patients, 29 at the maximum tolerated dose (MTD). The response rate in 38 evaluable patients was 63% (95% confidence interval (CI): 49-80). Median time to progression and overall survival were 8.7 months (95% CI: 7.9-10.4) and 16.8 months (95% CI: 9.6-25.3), respectively. In the MTD group, one patient had grade 3 leucopenia; one had grade 3 neutropaenia; three had grade 3 diarrhoea; and one had grade 3 neurotoxicity. No hand-foot syndrome grade >1 was seen. In total, 67% of eligible patients received second-line therapy. UFT plus LV with alternating irinotecan and oxaliplatin is an efficacious first-line treatment for mCRC, with minimal neurotoxicity and hand-foot syndrome.
    • A patient with a metastatic gastroenteropancreatic endocrine carcinoma causing hyperinsulinaemic hypoglycaemia and the carcinoid syndrome.

      Hinchliffe, E; Allcock, R L; Mansoor, Was; Myers, M A; Department of Clinical Biochemistry, University Hospital of South Manchester, Wythenshawe, Manchester M23 9LT, UK. (2011-11)
      We present the case of a 57-year-old patient who initially presented with a constellation of symptoms including intense pruritis, flushing and diarrhoea. Following several months clinical deterioration, the patient was investigated radiologically, where multiple hepatic tumours were identified. Liver biopsy confirmed the presence of a well-differentiated metastatic gastroenteropancreatic endocrine carcinoma with biochemical evidence of serotonin secretion. Over a period of six months, the clinical course of the patient's disease progressed whereby severe hypoglycaemia became the major manifestation. Subsequent biochemical investigations confirmed the diagnosis of an insulinoma. Extensive radiological investigation revealed a solitary primary pancreatic tumour, indicating the presence of a metastatic pancreatic endocrine tumour (PET) secreting both insulin and serotonin. The patient was treated with a chemotherapy regimen consisting of 12 cycles of 5-fluorouracil/oxaliplatin, responding clinically - improved World Health Organization performance score from 3 to 1, biochemically - significantly reduced plasma chromogranin A and cancer antigen 19-9 concentrations and improved liver function tests, and radiologically - reduced pancreatic and hepatic tumour size. This is the first report of a primary PET secreting insulin and serotonin. Due to the association of serotonin-secreting gastroenteropancreatic endocrine tumours (GEP-ETs) with multiple endocrine neoplasia type-1 (MEN1) and biochemical evidence of an insulinoma, MEN1 should also be considered in such cases. The case provides further evidence for the biological heterogeneity of GEP-ETs and the myriad secretory humoral products and resultant clinical syndromes arising from such tumours.