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Pancreatic cancer is a malignancy with a very poor prognosis, even when radically resected. In advanced disease chemotherapy has a role in terms of clinical benefit and symptoms palliation, more than survival advantage. Gemcitabine as a single agent is the first-line standard treatment since 1997. Several trials failed to demonstrate a survival advantage of chemotherapy doublets or gemcitabine combined with biological agents versus gemcitabine alone in phase III trials. Erlotinib was the only agent to produce a statistically significant improvement of survival when combined with gemcitabine versus gemcitabine alone. Nevertheless, the clinical application of these literature data remains controversial. However, a meta-analysis showed that combination chemotherapy is superior to gemcitabine alone in terms of survival and clinical benefit in selected subgroups of patients. In unresectable locally advanced disease chemotherapy is active, whereas no high level evidence exists about a possible superiority of chemoradiation. Chemotherapy followed by chemoradiation represents a promising treatment schedule, resulting better than chemotherapy alone in a retrospective analysis. Adjuvant chemotherapy is nowadays a standard treatment, with both 5-FU and gemcitabine resulted superior to observation. Instead adjuvant chemoradiation is not a standard, even though it can be suggested in selected subgroups of patients. In resectable locally advanced disease neoadjuvant therapy is still investigational. Chemoradiation or chemotherapy followed by chemoradiation produced promising results in phase II trials. Possible future gain in terms of survival could come from better neoadjuvant treatments in potentially resectable pancreatic carcinoma. Therefore, this setting should stimulate studies with new drugs and combinations and potential biological predictive factors.

Purpose: Second-line chemotherapy in patients with metastatic gastric cancer (MGC) pre-treated with cisplatin is not a standard option. We studied a combination of irinotecan, fluorouracil and folates., Methods: Patients progressive to cisplatin-based chemotherapy were enrolled. Irinotecan 180 mg/m(2), folinic acid 200 mg/m(2), and fluorouracil 400 mg/m(2) were given on day 1, immediately followed by fluorouracil 2,400 mg/m(2) 46 h continuous infusion (simplified FOLFIRI), every 2 weeks., Results: Between June 2002 and May 2003, 28 patients were treated. Median age was 57 years (range 38-68). Most patients had a distal primary (90%), and metastatic disease (71%). Partial response was obtained in six patients (21%, 95% CI 8-41) and stable disease in eight (21%, 95% CI 13-41). Among the six responsive patients three were refractory to docetaxel. At a median follow-up of 2.9 years median time to progression was 4 months (95% CI: 2-5), and median overall survival was 5 months (95% CI 4-9). Toxicity was mild, without treatment-related deaths or life-treating adverse events., Conclusions: Simplified FOLFIRI was moderately active and well tolerated in unselected patients with MGC pre-treated with cisplatin-based chemotherapy. Its role in patients refractory to taxanes is promising and warrants further investigation.