Calcium and antioxidant vitamins, such as A, C, and E, have been shown to reduce colorectal epithelial proliferation and thereby to act as possible chemoprotective agents in colorectal cancer. We investigated the effects of an intervention with calcium and vitamins on cell proliferation in the colonic mucosa of patients operated on for colorectal cancer. Patients with resected colorectal cancer Dukes' stage B-C were randomized to receive daily 30,000 IU of axerophthol palmitate (vitamin A) plus 1 g ascorbic acid (vitamin C) plus 70 mg of dl-alpha-tocopherol acetate (vitamin E) and 2 g natural calcium daily or indistinguishable placebo for 6 months. At the time of surgery and after 6 and 12 months of treatment, cell kinetics of normal colonic mucosa were assessed by using proliferating cell nuclear antigen (PCNA). Ninety patients were enrolled and 77 were assessable: 34 in the treatment group and 43 in the placebo group. A significant reduction of mean total PCNA labeling index (PCNALI) was evident in both groups after 6 months (vitamins/calcium, from 16.11 +/- 2.43 to 10.71 +/- 2.81; placebo, from 17.30 +/- 2.63 to 12.53 +/- 3.40). The difference in the percentage of reduction of mean PCNALI between baseline and after 6 months was not statistically significant in the treatment and placebo groups: 34% and 28%, respectively. A second control, 6 months after discontinuation of vitamin and calcium supplementation, showed a further decrease of mean total PCNALI in both groups, but this was not statistically significant. Our randomized trial showed that calcium and vitamin supplementation does not reduce cell kinetics of colon epithelium. Furthermore, this study suggests the need for extreme caution in the interpretation and publication of studies on chemoprotectants in colon cancer without a control group.

No abstract

No abstract

4031 Background: Aim of this study was to evaluate efficacy and safety of cetuximab plus FOLFIRI as first-line treatment for advanced gastric or GEJ cancer. Methods: Eligibility criteria: histological diagnosis of stomach or GEJ adenocarcinoma, unresectable/metastatic/recurrent disease, EGFR+ (Dako), measurable disease, no prior chemotherapy for advanced cancer. Pts received cetuximab weekly at 400 mg/m2 iv loading dose, then at 250 mg/m2 iv, CPT11 180 mg/m2 iv d1, LFA 100 mg/m2 iv followed by 5FU 400 mg/m2 iv bolus and 600 mg/m2 iv continuous infusion 22h d1–2 (FOLFIRI) every 2 weeks, for a maximum of 24 weeks, then cetuximab alone was allowed in pts with CR/PR/SD. Objective response (OR) activity was assessed by CT and PET at baseline and after 6 weeks, and further by CT± PET every 6 weeks. Results: From November 2004 to December 2005, 49/54 (90.7%) screened subjects were EGFR+, and 38 pts were enrolled. Pt characteristics: 26 (68.4%) males, 12 (31.6%) females; median age 63.5 years (39–82); median KPS 90 (70–100); 34 (89.4%) stomach, 4 (10.5%) GEJ; 18 (47.3%) gastrectomy; 13 (34.2%) adjuvant chemotherapy; 4 (10.5%) locally advanced disease, 34 (89.4%) metastatic disease; main metastatic sites: 19 (50%) lymphonodes, 12 (31.5%) liver, 4 (10.5%) lung, 8 (21.0%) peritoneal. Median number of treatment weeks was: 10 (1–46). Median dose intensity was: 5FU 100% (25–100), CPT11 100% (25–100) and cetuximab 100% (80–100). At the present time, 25 pts are assessable for response and 28 for toxicity. The OR (RECIST) were: 3 (12%) CR,11 (44%) PR, e.g. 56% CR + PR (95% CI: 37–75), 11 (44%) SD. The PFS at 3 months is 80% (95% CI: 64–96). Survival data are premature (73.6% of the pts are alive; median follow-up 3 months, range 1–12). Grade 3–4 toxicity (CTC v3.0) was: 15 (53.6%) neutropenia (1 pt died of febrile neutropenia), 1 (3.4%) thrombocytopenia, 2 (6.8%) hypertransaminasemia, 1 (3.4%) hyperbilirubinemia. Cutaneous toxicity was: 7 (25%) gr1, 11 (39.2%) gr2, 5 (17.8%) gr3. Conclusions: Combination of cetuximab and FOLFIRI appears to be active in gastric and GEJ adenocarcinoma, with a high response and disease control rate. This treatment has been well-tolerated; the major toxicity is neutropenia. No significant financial relationships to disclose.

No abstract