British journal of cancer
-
British journal of cancer · Dec 1994
Randomized Controlled Trial Clinical TrialComparison of granisetron alone and granisetron plus dexamethasone in the prophylaxis of cytotoxic-induced emesis.
Two hundred and seventy-eight adult chemonaive patients, receiving moderately emetogenic chemotherapy were randomly allocated to receive either intravenous (i.v.) granisetron 3 mg plus i.v. dexamethasone 8 mg or i.v. granisetron 3 mg plus i.v. placebo dexamethasone prior to chemotherapy. Eight-two per cent of all patients recruited were female, and 91% of all patients consumed less than 10 units of alcohol per week, suggesting a study population with an increased risk of nausea and vomiting. ⋯ Toxicity was minimal with no significant differences between treatment groups. These results confirm the antiemetic activity of granisetron and show that it has an additive effect in combination with dexamethasone.
-
British journal of cancer · Dec 1994
Linkage studies in a Li-Fraumeni family with increased expression of p53 protein but no germline mutation in p53.
We report a family with the Li-Fraumeni syndrome (LFS) in whom we have been unable to detect a mutation in the coding sequence of the p53 gene. Analysis of linkage to three polymorphic markers within p53 enabled direct involvement of p53 to be excluded. This is the first example of a LFS family in whom exclusion of p53 has been possible. ⋯ Therefore MDM2 could be excluded. It is possible that the gene which is responsible for cancer susceptibility in this family, possibly via interaction with p53, will be important in the histogenesis of breast cancer in general. We are now carrying out further studies to locate and identify this gene.
-
British journal of cancer · Aug 1994
Multicenter Study Clinical TrialDocetaxel (Taxotere) is active in non-small-cell lung cancer: a phase II trial of the EORTC Early Clinical Trials Group (ECTG)
In a multicentre trial of the EORTC ECTG we have treated 43 non-pretreated patients with advanced non-small-cell lung cancer (NSCLC) with the new semisynthetic taxoid docetaxel (Taxotere). Six patients were ineligible; of the 37 eligible patients, ten had prior radiotherapy and 18 prior surgery. They received 100 mg m-2 in 1 h i.v. every 3 weeks, usually in an outpatient setting. ⋯ Stable disease was found in 16 patients. The median duration of response was 36 weeks, and the median survival of all patients was 11 months. Docetaxel (Taxotere) is among the most active drugs for treatment of NSCLC.
-
British journal of cancer · Jan 1994
Randomized Controlled Trial Comparative Study Clinical TrialA randomised study with subcutaneous low-dose interleukin 2 alone vs interleukin 2 plus the pineal neurohormone melatonin in advanced solid neoplasms other than renal cancer and melanoma.
Our previous experimental studies have shown that the best approach to increase the biological anti-tumour activity of interleukin 2 (IL-2) is not co-administration of another cytokine, but the association with immunomodulating neurohormones, in an attempt to reproduce the physiological links between psychoendocrine and immune systems, which play a fundamental role in the regulation of the immune responses. In particular, the association with the pineal neurohormone melatonin (MLT) has been shown to cause tumour regressions in neoplasms that are generally non-responsive to IL-2 alone. To confirm these preliminary results, a clinical trial was performed in locally advanced or metastatic patients with solid tumours other than renal cell cancer and melanoma. ⋯ Finally, the mean increase in lymphocyte and eosinophil number was significantly higher in the IL-2 plus MLT group than in patients treated with IL-2 alone; on the contrary, the mean increase in the specific marker of macrophage activation neopterin was significantly higher in patients treated with IL-2 alone. The treatment was well tolerated in both groups of patients. This study shows that the concomitant administration of the pineal hormone MLT may increase the efficacy of low-dose IL-2 subcutaneous therapy.
-
A clinical trial conducted according to a schedule of interim analyses written into the protocol, and stopped according to a predetermined rule, is known to statisticians as a sequential clinical trial. This methodology is becoming more widely used in trials concerning life-threatening diseases because of its ability to adjust the sample size to the emerging information on treatment efficacy. When treatments under comparison differ appreciably, small samples will be sufficient; for more subtle differences larger numbers of patients need to be recruited. ⋯ In this paper the principles of sample size determination are reviewed, and the essential aspects of designing sequential trials are described. The necessity for a special form of statistical analysis following a sequential trial is explained, and the consequences of early or late stopping on the analysis are investigated. Compromises which have to be made between the formal requirements of theory and the practical realities of trial conduct are discussed.