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Although the treatment of pancreatic ductal adenocarcinoma (PDAC) remains a huge challenge, it is entering a new era with the development of new strategies and trial designs. Because there is an increasing number of novel therapeutic agents and potential combinations available to test in patients with PDAC, the identification of robust prognostic and predictive markers and of new targets and relevant pathways is a top priority as well as the design of adequate trials incorporating molecular-driven hypothesis. We presently report a consensus strategy for research in pancreatic cancer that was developed by a multidisciplinary panel of experts from different European institutions and collaborative groups involved in pancreatic cancer. The expert panel embraces the concept of exploratory early proof of concept studies, based on the prediction of response to novel agents and combinations, and randomised phase II studies permitting the selection of the best therapeutic approach to go forward into phase III, where the recommended primary end point remains overall survival. Trials should contain as many translational components as possible, relying on standardised tissue and blood processing and robust biobanking, and including dynamic imaging. Attention should not only be paid to the pancreatic cancer cells but also to microenvironmental factors and stem/stellate cells. [ABSTRACT FROM PUBLISHER]

To assess the efficacy of the combination of long-acting release (LAR) octreotide and tamoxifen (TMX) for the treatment of advanced hepatocellular carcinoma (HCC). A total of 109 patients with advanced HCC were randomised to receive octreotide LAR combined with TMX (n=56) (experimental treatment group) or TMX alone (n=53; control group). The clinical, biological and tumoural parameters were recorded every 3 months until death. Primary end point was patient survival; secondary end points were the impact of therapy on tumour response, quality of life and variceal bleeding episodes. Univariate and multivariate analyses were performed for assessment of specific prognostic factors. The median survival was 3 months (95% CI 1.4–4.6) for the experimental treatment group and 6 months (CI 95% 2–10) for the control group (P=0.609). There was no difference in terms of α-foetoprotein (α-FP) decrease, tumour regression, improvement of quality of life and prevention of variceal bleeding between the two groups. Variables associated with a better survival in the multivariate analysis were: presence of cirrhosis, α-FP level <400 ng ml−1 and Okuda stage I. The combination of octreotide LAR and TMX does not influence survival, tumour progression or quality of life in patients with advanced HCC.British Journal of Cancer (2007) 97, 582–588. doi:10.1038/sj.bjc.6603901 www.bjcancer.com Published online 7 August 2007 [ABSTRACT FROM AUTHOR]

Background: Gemcitabine monotherapy is the cornerstone of the treatment of patients suffering from advanced pancreatic cancer (PC). For a few years, new chemotherapeutic agents and combinations have been under validation. The use of such treatment makes it necessary to determine factors that could predict survival time. Patients and Methods: To identify factors that predict survival time in chemonaïve patients with advanced PC and after gemcitabine failure, a retrospective analysis was performed on patients with advanced PC coming from phase II and III studies and treated with gemcitabine-based first-line chemotherapy. Results: Ninety-nine patients (median age 66 years, range 27–87) suffering from pathologically proven unresectable or metastatic adenocarcinoma of the pancreas were reviewed. Median overall survival time for the whole population was 251 days and progression-free survival in first- and second-line treatment was 108 and 67 days, respectively. The Cox regression analysis identified aspartate transaminase >53 IU/l, weight loss ≥10% and Karnofsky performance status <90 as significant independent negative prognostic factors in first-line and CA 19-9 >400 IU/ml and albumin ≤3.5 mg/dl in second-line chemotherapy. A prognostic index was calculated from the regression coefficients for each independent prognostic factor and used to classify the patients in 3 different groups with good, intermediate and poor prognosis. The prognosis index in chemonaïve and gemcitabine-refractory patients was (Karnofsy performance status × 0.52) + (weight loss × 1.10) + (aspartate transaminase × 0.82) and (albumin × 1.40) + (CA 19-9 × 0.74), respectively. Conclusions: Predictive factors could be identified in first- and second-line treatments, although they require prospective validation before they could be used in the design and analysis of future clinical trials. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Gemcitabine and oxaliplatin (GEMOX) are active as first-line therapy against advanced pancreatic cancer. This study aims to evaluate the activity and tolerability of this combination in patients refractory to standard gemcitabine (GEM). A total of 33 patients (median age of 57) were included with locally advanced and metastatic evaluable diseases, who had progressed during or following GEM therapy. The GEMOX regimen consisted of 1000 mg m−2 of GEM at a 100-min infusion on day 1, followed on day 2 by 100 mg m−2 of oxaliplatin at a 2-h infusion; a cycle that was given every 2 weeks. All patients received at least one cycle of GEMOX (median 5; range 1–29). Response by 31 evaluable patients was as follows: PR: 7/31(22.6%), s.d. 8 weeks: 11/31(35.5%), s.d. <8 weeks: 1/31(3.2%), PD: 12/31(38.7%). Median duration of response and TTP were 4.5 and 4.2 months, respectively. Median survival was 6 months (range 0.5–21). Clinical benefit response was observed in 17/31 patients (54.8%). Grade III/IV non-neurologic toxicities occurred in 12/33 patients (36.3%), and grade I, II, and III neuropathy in 17(51%), 3(9%), and 4(12%) patients, respectively. GEMOX is a well-tolerated, active regimen that may provide a benefit to patients with advanced pancreatic cancer after progression following standard gemcitabine treatment.British Journal of Cancer (2006) 94, 481–485. doi:10.1038/sj.bjc.6602966 www.bjcancer.com Published online 24 January 2006 [ABSTRACT FROM AUTHOR]

Objectives: This multicenter phase II study was designed to determine the activity and tolerance of gemcitabine and raltitrexed in advanced pancreatic adenocarcinoma. Patients andMethods: Thirty-three chemonaive patients with measurable disease received the TOMGEM regimen consisting of Raltitrexed 3 mg/m2 in 15 min followed by Gemcitabine 1,000 mg/m2 in 30 min on day 1, Gemcitabine alone 1,000 mg/m2 on day 8 and repeated on day 21. Results: Thirty-three patients (median age: 62; locally advanced/metastatic disease: 5/28) were enrolled; the total number of cycles administered was 173 (median: 4). There were 10 partial response (confirmed), 2 stable disease (SD) ≥24 weeks, 7 SD <24 weeks, and 14 progressive disease for a response rate of 30.3% (95% CI: 14–46%); a clinical benefit was observed in 8/30 patients assessed (30%); median duration of response was 9.1 months. National Cancer Institute Common Toxicity Criteria grade III or IV neutropenia/thrombocytopenia were observed in 42 and 12% of the patients, respectively. Relevant nonhematological toxicities (grade III–IV) were rare although one toxic death was observed. Median time to progression was 2.8 months; one-year survival was 21%; median survival was 4.7 months. Conclusion: Our data suggest that the combination of raltitrexed/gemcitabine is a very convenient regimen with an acceptable toxicity, and is active in advanced pancreatic cancer. Copyright © 2004 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Over the past few years, different endoscopic ablative techniques have been used in combination with antireflux therapy with the aim of reversing Barrett's oesophagus and replacing it with squamous epithelium. The end goal of these procedures is to impact directly on the risk of tumor development. Results provided by the present randomized study are relatively similar to those reported in previous ones which assessed a single modality, particularly with regard to treatment procedures, median length of Barrett's oesophagus, proton pump inhibitor therapy, and duration of follow up.

Background Cholangiocarcinomas are uncommon tumours with a poor prognosis, that frequently present epidermal growth factor receptor overexpression. Methods In a multi-centre phase II trial, patients with unresectable cholangiocarcinoma, naïve to chemotherapy, received Cetuximab (400 mg/m2 at week 1, then 250 mg/m2/week) and Gemcitabine (1 g/m2 on day 1, 8 and 15 every 4 weeks). Primary end point was progression-free survival (PFS) rate at 6 months, using a Simon 2-stage design. Moreover, we assessed the impact of KRAS status and skin toxic effect on efficacy. Results Forty-four patients (41% locally advanced/59% metastatic) were enrolled. Median age was 61.5 years; ECOG PS was 0 (68%) or 1. Six months PFS reached 47%. Median OS was 13.5 months [95% confidence interval (CI) 9.8–31.8 months]. Nine patients (20.4%) had PR and disease-control rate was 79.5%. Grade 3/4–related toxic effects were haematological (52.2%), skin rash (13.6%) and fatigue (11.4%). KRAS mutations were found in 7 of 27 patients and had no influence on PFS. Skin toxic effect ≥grade 2 was associated with increased PFS (P = 0.05). Conclusion(s) Our study met its primary end point, suggesting that Gemcitabine-Cetuximab has activity in cholangiocarcinoma. KRAS status was not associated with PFS, unlike skin toxic effect, which could be used as a surrogate marker for efficacy. [ABSTRACT FROM PUBLISHER]