Biology of cancer invasion and metastasis.

Current concepts of invasion eventually leading to metastasis are discussed and exemplified by cancers of the head and neck mucosa. Invasion occurs at a number of steps, each step making an ecosystem comprising not only the neoplastic cells but also their normal counterparts, a variety of host cells and the extracellular matrix. The ecosystem concept may explain aspects of metastasis such as site-dependence and organ-specificity of cancer metastasis as well as invasiveness of normal leucocytes. Genes implicated in invasion and metastasis are actively searched for. Recently, the epithelial cell-cell adhesion molecule E-cadherin has been identified as an i- (invasion suppressor) gene product, i.e. a molecule the expression of which counterbalances i+ (invasion promotor) gene activity. Downregulation of E-cadherin in human head and neck cancers may account for their invasive and metastatic behaviour.

Optimum anti-emetic therapy for cisplatin induced emesis over repeat courses: ondansetron plus dexamethasone compared with metoclopramide, dexamethasone plus lorazepam.

BACKGROUND: This study was undertaken to compare the efficacy and tolerability of ondansetron plus dexamethasone (O + D) with metoclopramide plus dexamethasone plus lorazepam (M + D + L) over three consecutive courses of cisplatin chemotherapy. PATIENTS AND METHODS: This was an international, multicentre, double-blind, double-dummy, parallel group study. O+D patients were randomised to receive ondansetron 8 mg intravenously (i.v.) plus dexamethasone 20 mg i.v. prior to cisplatin (50-100 mg/m2) chemotherapy. On the following 4 days they were treated with ondansetron 8 mg bd orally and dexamethasone 4 mg bd orally. M + D + L patients were randomised to receive metoclopramide 3 mg/kg i.v., dexamethasone 20 mg i.v. and lorazepam 1.5 mg/m2 i.v. (max 3 mg) prior to cisplatin chemotherapy and a further dose of metoclopramide 3 mg/kg i.v. approximately 2 hours following the first dose of metoclopramide. Treatment for the following 4 days was metoclopramide 40 mg tds and dexamethasone 4 mg bd orally. Two hundred and thirty-seven patients were recruited into the study (117 patients received O + D and 120 received M + D + L). RESULTS: On the first course chemotherapy, O + D was significantly superior to the M + D + L regimen for complete control of emesis (days 1-5, 54% versus 37%, respectively, P = 0.014). This was maintained over the three treatment cycles; 38% of O + D and 20% of M + D + L patients remained free of emesis (P = 0.003). Maintenance of control of nausea grade as none or mild on days 1-5 over the three courses was significantly better in the O + D group (48%) than in the M + D + L (26%, P = 0.003). The most commonly occurring adverse events in the O + D group were constipation (25%) and headache (19%). In the M + D + L group drowsiness (38% of patients), malaise/fatigue (16% of patients), constipation (13% of patients), anxiety (11% of patients) and dizziness (10% of patients) were the most commonly reported adverse events. Extrapyramidal symptoms were reported by 20% of patients in the M + D + L group. Despite the inclusion of lorazepam, 14% of patients in the M + D + L group were withdrawn from the study due to extrapyramidal symptoms, which in the opinion of the investigators, were probably or almost certainly related to study medication. CONCLUSION: This study show that O + D is significantly more effective and better tolerated than M + D + L for the control of emesis and nausea over a series of three courses of cisplatin chemotherapy.