Colorectal cancer: screening

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A phase II study of sequential chemotherapy with docetaxel after the weekly PELF regimen in advanced gastric cancer. A report from the Italian group for the study of digestive tract cancer

In advanced gastric cancer, we investigated feasibility and activity of sequential chemotherapy with docetaxel after an intensive weekly regimen consisting of cisplatin, epidoxorubicin, fluorouracil, leucovorin (PELF) plus filgrastim. Chemotherapy-naive patients with relapsed or metastatic gastric cancer received 8 weekly administrations of chemotherapy with cisplatin 40 mg/m2, fluorouracil 500 mg/m2,epi-doxorubicin 35 mg/m2, 6S-steroisomer of leucovorin 250 mg/m2and glutathione 1.5 g/m2. On the other days filgrastim 5 μg kg–1was administered by subcutanous injection. Subsequently, patients with partial response or stable disease received 3 cycles of docetaxel 100 mg/m2every 3 weeks. 40 patients have been enrolled and they are evaluable for response and toxicity. After the PELF regimen, 3 patients achieved complete response, 13 patients showed partial response, 21 patients had stable disease and 3 patients progressed (40% response rate; 95% CI 25% to 55%). After docetaxel, 9 out 34 patients improved the outcome (26.5%); 7 patients with stable disease achieved partial response and 2 patients with partial response achieved complete response. The overall response rate in the 40 patients was 57.5% (95% CI, 42.5% to 72.5%). The PELF regimen did not cause any grade IV toxicity, the most frequent grade III acute side-effects were thrombocytopenia and vomiting which occurred in the 10% of 320 PELF cycles. Docetaxel caused grade III–IV neutropenia and thrombocytopenia in the 10% and the 19% of cycles respectively. Fatigue was a frequent side-effect during both PELF and docetaxel chemotherapy. The sequential application of docetaxel after PELF chemotherapy gained major objective responses with manageable toxicity. This strategy is worth of further investigation in the setting of palliative or neoadjuvant chemotherapy. © 2001 Cancer Research Campaign http://www.bjcancer.co

Effectiveness of direct egfr mutations research at time of diagnostic biopsy for lung cancer: a single institution outcome research

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5-fluorouracil modulated by leucovorin, methotrexate and mitomycin: highly effective, low-cost chemotherapy for advanced colorectal cancer

We have reported that an alternating regimen of bolus and continuous infusion 5-fluorouracil (FU) was superior to bolus FU in terms of response rate and progression-free survival in advanced colorectal cancer. Biochemical modulation was an essential part of this regimen and it was selective for the schedule of FU administration: bolus FU was in fact modulated by methotrexate (MTX) while continuous infusion FU was potentiated by 6-s-leucovorin (LV). Considering the low cost and the favourable report on the activity of mitomycin C (mito) added to CI FU, we have incorporated this agent in the infusional part of our treatment programme. 105 patients with untreated, advanced, measurable colorectal cancer were accrued from 13 Italian centres and treated with the following regimen. 2 biweekly cycles of FU bolus (600 mg/m2), modulated by MTX (24 h earlier, 200 mg/m2) were alternated with a 3-week continuous infusion of FU (200 mg/m2daily), modulated by LV (20 mg/m2weekly bolus). Mito, 7 mg/m2, was given on the first day of the infusional period. After a 1 week rest, the whole cycle (8 weeks) was repeated, if indicated. 5 complete and 34 partial responses were obtained (response rate, 37% on the intention to treat basis; 95% confidence limits, 28–46%). After a median follow-up time of 26 months, 37 patients are still alive. The median progression-free survival is 7.7 months with an overall survival of 18.8 months and a 2-year survival rate of 30%. The regimen was very well tolerated with fewer than 13% of patients experiencing WHO grade III–IV toxicity. These results are consistent with those obtained by our group in 3 previous trials of schedule specific biochemical modulation of FU. They also indicate a highly active, little toxic, inexpensive regimen of old drugs to be used (a) as an alternative to the more expensive combinations including CPT-11 or oxaliplatin or (b) as the basis for combination programmes with these agents. © 2001 Cancer Research Campaign http://www.bjcancer.co

FOLFOX4/XELOX in stage II–III colon cancer: Efficacy and safety results of the Italian Three Or Six Colon Adjuvant (TOSCA) trial

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p 291the distinctive study a biologically enriched phase ii study of second line folfiri aflibercept in prospectively stratified anti egfr resistant metastatic colorectal cancer patients with ras validated wild type status trial in progress

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From central to sentral (Serum angiogenesis central): Circulating predictive biomarkers to anti-VEGFR therapy

Background: In the last decade, a series of analyses failed to identify predictive biomarkers of resistance/susceptibility for anti-angiogenic drugs in metastatic colorectal cancer (mCRC). We conducted an exploratory preplanned analysis of serum pro-angiogenic factors (SErum aNgiogenesis-cenTRAL) in 72 mCRC patients enrolled in the phase II CENTRAL (ColorEctalavastiNTRiAlLdh) trial, with the aim to identify potential predictive factors for sensitivity/resistance to first line folinic acid-fluorouracil-irinotecan regimen (FOLFIRI) plus bevacizumab. Methods: First-line FOLFIRI/bevacizumab patients were prospectively assessed for the following circulating pro-angiogenic factors, evaluated with ELISA (enzyme-linked immunosorbent assay)-based technique at baseline and at every cycle: Vascular endothelial growth factor A (VEGF-A), hepatocyte growth factor (HGF), stromal derived factor-1 (SDF-1), placental derived growth factor (PlGF), fibroblast growth factor-2 (FGF-2), monocyte chemotactic protein-3 (MCP-3), interleukin-8 (IL-8). Results: Changes in circulating FGF-2 levels among different blood samples seemed to correlate with clinical outcome. Patients who experienced an increase in FGF-2 levels at the second cycle of chemotherapy compared to baseline, had a median Progression Free Survival (mPFS) of 12.85 vs. 7.57 months (Hazard Ratio—HR: 0.73, 95% Confidence Interval—CI: 0.43-1.27, p = 0.23). Similar results were seen when comparing FGF-2 concentrations between baseline and eight-week time point (mPFS 12.98 vs. 8.00 months, HR: 0.78, 95% CI: 0.46–1.33, p = 0.35). Conclusions: Our pre-planned, prospective analysis suggests that circulating FGF-2 levels’ early increase could be used as a marker to identify patients who are more likely to gain benefit from FOLFIRI/bevacizumab first-line therapy

prognostic value of neutrophil lymphocite ratio in resected high risk colorectal cancer an analysis of adjuvant tosca trial

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