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Background: The aim was to investigate the outcomes associated with venous thromboembolism (VTE) among irresectable pancreatic cancer patients. Methods: This is a follow-up study of consecutive irresectable cancer patients, treated and followed up in clinical trials between December 2001 and December 2004 in order to evaluate the prognostic impact of symptomatic VTE on clinical outcomes, such as response to treatment, progression-free survival (PFS) and overall survival (OS). Results: Among 227 irresectable pancreatic cancer patients, with Eastern Cooperative Oncology Group performance status (ECOG-PS) ≤ 2, 59 (26.0%) patients developed a VTE. A synchronous VTE occurred in 28 (12.3%) patients, while a VTE during chemotherapy was observed in 15 (6.6%) patients, and 16 (7.0%) patients experienced both events. Presence of synchronous VTE was associated with a higher probability of not responding to treatment (odds ratio 2.98, 95% CI 1.42–6.27, P = 0.004), but showed no effect on both PFS and OS at least at multivariate analysis. Occurrence of a VTE during chemotherapy showed a statistically significant effect on PFS (hazard ratio [HR] 2.59, 95% CI 1.69–3.97, P < 0.0001) and OS (HR 1.64, 95%CI 1.04–2.58, P = 0.032). Conclusions: Our data suggest that the occurrence of VTE may be associated with a reduced response rate and a shorter PFS and OS among patients with irresectable pancreatic cancer. In these patients the development of VTE may reflect the presence of a biologically more aggressive cancer that in turn leads to a worse prognosis. [ABSTRACT FROM AUTHOR]

Background: The purpose of this phase II study was to evaluate the efficacy and safety of cetuximab combined with FOLFIRI as a first-line treatment of advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma.Patients and methods: Untreated patients with confirmed advanced gastric or gastroesophageal adenocarcinoma received cetuximab at an initial dose of 400 mg/m2 intravenously (i.v.) followed by weekly doses of 250 mg/m2, CPT 11 180 mg/m2 i.v. on day 1, LFA 100 mg/m2 i.v. followed by 5-FU 400 mg/m2 i.v. bolus, and 600 mg/m2 i.v. 22-h continuous infusion on days 1 and 2 (FOLFIRI) every 2 weeks, for a maximum of 24 weeks, then cetuximab alone was allowed in patients with a complete response, partial response, or stable disease. Antitumor activity was assessed by computed tomography (CT) and positron emission tomography (PET) at baseline and after 6 weeks, and further by CT alone or CT and PET every 6 weeks.Results: Thirty-eight patients were enrolled (median age 63.5 years, range 39–83; median Karnofsky performance status 90, range 70–100; stomach 89.5% and GEJ 10.5%; locally advanced disease 13.2% and metastatic disease 86.8%). All 38 patients were assessed for safety and survival, and 34 patients were assessed for overall response rates (ORR). The ORR was 44.1% [95% confidence interval (CI) 27.5% to 60.9%]. The median time-to-progression was 8 months (95% CI 7–9). At the median follow-up time of 11 months, 55.3% of patients were alive, with a median expected survival time of 16 months (95% CI 9–23). Grade 3–4 toxicity included neutropenia (42.1%), acne-like rash (21.1%), diarrhea (7.9%), asthenia (5.3%), stomatitis (5.3%), and hypertransaminasemia (5.3%). There was one (2.6%) treatment-related death.Conclusions: The combination of cetuximab and FOLFIRI is active in gastric and GEJ adenocarcinoma. The higher toxicity appears to be limited to neutropenia. [ABSTRACT FROM AUTHOR]

The aim of our analysis was to assess retrospectively the effect on local relapse, overall survival (OS) and disease-free survival (DFS) of a limited or an extended lymphadenectomy in radically resected gastric cancer patients. This study was performed in order to identify a subgroup of patients possibly not benefiting from a therapeutic approach such as chemoradiation therapy. We divided our patients into two groups according to lymphadenectomy type: group A for limited (<25 resected lymph nodes) and group B for extended (>25 resected lymph nodes) lymph nodes resection. A total of 418 patients were analysed: tumour stage at diagnosis was pT2-3 pN1-3 M0 in 339 patients and pT3 N0 M0 in 79 patients. Median age at diagnosis was 68 years (range 30-92 years). A total of 306 patients (73.2%) were in group A and 112 (26.8%) in group B. The median survival time (OS) for patients in groups A and B was 58.8 and 84.8 months, respectively (P=0.0371); median DFS was 28.8 months in group A and 59.9 months in group B (P=0.0027). At multivariate analysis, extension within the gastric wall, nodal involvement and the number of resected lymph nodes appeared to affect both OS and DFS. An inadequate lymph nodes resection can affect survival and result in a higher incidence of local relapse, making the latter group of patients optimal candidates for adjuvant chemoradiation.British Journal of Cancer (2005) 92, 1051-1054. doi:10.1038/sj.bjc.6602468 www.bjcancer.com Published online 15 March 2005 [ABSTRACT FROM AUTHOR]

Background: Arterial hypertension occurring during antiangiogenic therapy has been correlated with the biological inhibition of the vascular endothelial growth factor-related pathway and may represent a possible clinical marker for treatment efficacy. The aim of our study was to retrospectively assess if grades 2–3 hypertension were associated with response to bevacizumab, progression-free survival (PFS) and survival in metastatic colorectal cancer patients treated with first-line bevacizumab. Patients and methods: Patients with histologically proven, metastatic colorectal cancer receiving bevacizumab as first-line therapy in combination with irinotecan and 5-fluorouracil were eligible for our analysis. Results: Thirty-nine metastatic colorectal cancer patients were eligible. Eight patients (20%) developed grades 2–3 hypertension. A partial remission was observed in six of eight cases with bevacizumab-related hypertension (75%) and in 10 of 31 (32%) patients with no hypertension (P = 0.04). Median PFS was 14.5 months for patients showing bevacizumab-related hypertension, while it was 3.1 months in those without hypertension (P = 0.04). Median overall survival was not reached in patients with hypertension while it was 15.1 months in the remaining cases (P = 0.11). Conclusions: Our data indicate that bevacizumab-induced hypertension may represent an interesting prognostic factor for clinical outcome in advanced colorectal cancer patients receiving first-line bevacizumab. [ABSTRACT FROM AUTHOR]

Background: The expression of the insulin-like growth factor (IGF) system has never been studied in gastrointestinal stromal tumors (GISTs). Patients and methods: We studied the immunohistochemical expression of IGF1 receptor (IGFR-I), IGF1 and IGF2 in 94 samples of GISTs. IGF1 and IGF2 expression was scored in three classes: negative (N), moderate (M) and strong (S), according to staining intensity and extent. Results: IGFR-I was overexpressed in all cases. IGF1 and IGF2 expression was absent in 25 and 48 cases, moderate in 29 and 16 cases and strong in 40 and 30 cases, respectively. Strong IGF1 expression significantly correlated with higher mitotic index (P = 0.0001), larger (P = 0.01), higher risk (P = 0.0002), metastatic (P = 0.0001) and relapsed (P = 0.04) GISTs. Strong IGF2 expression correlated with higher mitotic index (P = 0.05) and higher risk GISTs (P = 0.001). The Kaplan–Meier analysis (N versus M versus S) showed a significant worsening of the disease-free survival (DFS) with the increase of IGF1 (P = 0.02) and IGF2 (P = 0.02) expression. In the subgroup of patients with operated high-risk GISTs, there was a better trend in DFS for patients affected by GISTs with negative IGF1 and IGF2. Conclusions: The expression of IGF1 and IGF2 seems to predict relapse in GIST patients. [ABSTRACT FROM AUTHOR]

Background: The prognostic significance of KIT or platelet-derived growth factor receptor α (PDGFRα) mutations in gastrointestinal stromal tumors (GISTs) is still controversial. Patients and methods: In all, 104 patients were diagnosed with GISTs by KIT immunoreactivity; tumor DNA was sequenced for the presence of mutations in KIT exons 9, 11, 13 and 17 and in PDGFRα exons 12 and 18. Disease-free survival (DFS) was analyzed in 85 radically resected patients. Results: KIT mutations occurred in exon 11 (69), in exon 9 (11) and in exon 17 (1). PDGFRα mutations were detected in exon 18 (10) and in exon 12 (3). Ten GISTs were wild type. Exon 11 mutations were as follows: deletions in 42 cases and point mutations in 20 cases and insertions and duplications, respectively, in 2 and 5 cases. A better trend in DFS was evident for duplicated and point-mutated exon 11 KIT GISTs. There was a significant association between PDGFRα mutations, gastric location and lower mitotic index. Moreover, PDGFRα-mutated GISTs seemed to have a better outcome. Conclusions: Point mutations and duplications in KIT exon 11 are associated with a better clinical trend in DFS. PDGFRα-mutated GISTs are preferentially localized in the stomach and seem to have a favorable clinical behavior. [ABSTRACT FROM AUTHOR]

This article summarizes the expert discussion on the management of pancreatic cancer, which took place during the 8th World Congress on Gastrointestinal Cancer in June 2006 in Barcelona. A multidisciplinary approach to a patient with pancreatic cancer is essential, in order to guarantee an optimal staging, surgery, selection of the appropriate (neo-)adjuvant strategy and chemotherapeutic choice management. Moreover, optimal symptomatic management requires a dedicated team of health care professionals. Quality control of surgery and pathology is especially important in this disease with a high locoregional failure rate. There is now solid evidence in favour of chemotherapy in both the adjuvant and palliative setting, and gemcitabine combined with erlotinib, capecitabine or platinum compounds seems to be slightly more active than gemcitabine alone in advanced pancreatic cancer. There is a place for chemoradiotherapy in selected patients with locally advanced disease, while the role in the adjuvant setting remains controversial. Those involved in the care for patients with pancreatic cancer should be encouraged to participate in well-designed clinical trials, in order to increase the evidence-based knowledge and to make further progress. [ABSTRACT FROM AUTHOR]