Efficacy of triplet combination chemotherapy with oxaliplatin, irinotecan and capecitabine (OCX) in metastatic colorectal cancer in relation to RAS/RAF mutation status: results of a retrospective analysis.

BACKGROUND: The triplet combination of fluorouracil, oxaliplatin and irinotecan for metastatic colorectal cancer improves efficacy at the cost of increased toxicity. Preliminary reports indicate that triplet combination regimens might improve outcome in the RAS/RAF-mutated subgroup. PATIENTS AND METHODS: This retrospective analysis included 25 patients with metastatic colorectal cancer, who received treatment with OCX (oxaliplatin, irinotecan, capecitabine). The regimen consisted of oxaliplatin 70 mg/m2 on days 1 and 15, irinotecan 100 mg/m2 on days 8 and 22, and capecitabine 1,400 mg/m2 on days 1-29 every 5 weeks. KRAS, NRAS, and BRAF mutations were determined by Sanger sequencing. RESULTS: 23 patients received at least 1 cycle and were evaluable for efficacy. In 10 patients, a KRAS or BRAF mutation was detected. Partial remission rate was 61%, median progression-free survival 9.8 months, and median overall survival 32.9 months for all evaluable patients. No difference in efficacy was detected between the RAS/RAF wild-type and the mutant group. OCX was well tolerated with no grade 3/4 haematological events. Diarrhoea was the major non-haematological toxicity (24% grade 3). CONCLUSION: In this retrospective analysis, triplet chemotherapy with OCX was well tolerated and achieved encouraging efficacy in metastatic colorectal cancer irrespective of RAS/RAF mutation status.

Beneficial effect of sodium nitroprusside after coronary artery bypass surgery: pump function correlates inversely with cardiac release of proinflammatory cytokines.

The authors studied the relationship between cardiac cytokine release and pump function and whether low-dose application of sodium nitroprusside (SNP) improves cardiac performance during coronary artery bypass graft (CABG) creation. Cardiac reperfusion and application of nitric oxide have an influence on cytokine release. However, the functional consequences are unclear. Patients with CABGs (n = 30) with severely compromised left ventricular ejection fraction (<40%) were treated with either SNP (0.5 microg/kg/min) or placebo for the first 60 minutes of reperfusion after cardiac arrest. Interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-alpha were determined in blood samples from the radial artery and coronary sinus during reperfusion (5, 35, and 75 minutes). Hemodynamic measurements were performed before and after cardiopulmonary bypass and at the end of surgery. In all patients, the cardiac index at the end of surgery correlated negatively with levels of TNF-alpha at 5 minutes (r = 0.398; P < 0.05), IL-8 at 35 minutes (r = 0.394; P < 0.05), and IL-6 at 75 minutes of reperfusion (r = 0.421; P < 0.025). Sodium nitroprusside improved the cardiac index immediately after reperfusion (4.4 L/min/m2 +/- 0.3 vs. 3.7 L/min/m2 +/- 0.1; P = 0.014) and at the end of surgery (3.8 L/min/m2 +/- 0.3 vs. 3.0 L/min/m2 +/- 0.2; P = 0.023). The negative correlation between cardiac index and transcardiac cytokines suggests that reducing cardiac inflammatory reaction improves postischemic cardiac function. This was achieved by treating CABG patients with the nitric oxide donor SNP at a dosage without vasodilatory action.