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Background:Ovarian cancer is the leading cause of death among cancers of the female genital tract, with poor outcomes despite chemotherapy. There was a persistent socioeconomic gradient in 1-year survival in England and Wales for more than 3 decades (1971-2001). Inequalities in 5-year survival persisted for more than 20 years but have been smaller for women diagnosed around 2000. We explored one possible explanation.Methods:We analysed data on 1406 women diagnosed with ovarian cancer during 1991-1998 and recruited to one of two randomised clinical trials. In the second International Collaborative Ovarian Neoplasm (ICON2) trial, women diagnosed between 1991 and 1996 were randomised to receive either the three-drug combination cyclophosphamide, doxorubicin and cisplatin (CAP) or single-agent carboplatin given at optimal dose. In the ICON3 trial, women diagnosed during 1995-1998 were randomised to receive either the same treatments as ICON2, or paclitaxel plus carboplatin.Relative survival at 1, 5 and 10 years was estimated for women in five categories of socioeconomic deprivation. The excess hazard of death over and above background mortality was estimated by fitting multivariable regression models with Poisson error structure and a dedicated link function in a generalised linear model framework, adjusting for the duration of follow-up and the confounding effects of age, Federation of Gynecology and Obstetrics (FIGO) stage and calendar period.Results:Unlike women with ovarian cancer in the general population, no statistically significant socioeconomic gradient was seen for women with ovarian cancer treated in the two randomised controlled trials. The deprivation gap in 1-year relative survival in the general population was statistically significant at −6.7% (95% CI (−8.1, −5.3)), compared with −3.6% (95% CI (−10.4, +3.2)) in the trial population.Conclusions:Although ovarian cancer survival is significantly lower among poor women than rich women in England and Wales, there was no evidence of an association between socioeconomic deprivation and survival among women with ovarian cancer who were treated and followed up consistently in two well-conducted randomised controlled trials. We conclude that the persistent socioeconomic gradient in survival among women with ovarian cancer, at least for 1-year survival, may be due to differences in access to treatment and standards of care. [ABSTRACT FROM AUTHOR]

Background: To speed up the evaluation of new therapies, the multi-arm, multi-stage trial design was suggested previously by the authors. Methods: In this paper, we evaluate the performance of the two-stage, multi-arm design using four cancer trials conducted at the MRC CTU. The performance of the design at fictitious interim analyses is assessed using a conditional bootstrap approach. Results: Two main aims are addressed: the error rate of correctly carrying on/stopping the trial at an interim analysis as well as quantifying the gains in terms of resources by employing this design. Furthermore, we make suggestions for the best timing of this interim analysis. Conclusion: Multi-arm, multi-stage trials are an effective way of speeding up the therapy evaluation process. The design performs well in terms of the type I and II error rates. [ABSTRACT FROM AUTHOR]

There is strong evidence that colorectal cancer survival differs between socioeconomic groups. We analysed data on 2481 patients diagnosed during 1989-1997 and recruited to a randomised controlled clinical trial (AXIS, ISRCTN32414363) of chemotherapy and radiotherapy for colorectal cancer. Crude and relative survival at 1 and 5 years was estimated in five categories of socioeconomic deprivation. Multiple imputation was used to account for missing data on tumour stage. A multivariable fractional polynomial model was fitted to estimate the excess hazard of death in each deprivation category, adjusting for the confounding effects of age, stage, cancer site (colon, rectum) and sex, using generalised linear models. Relative survival in the trial patients was higher than in the general population of England and Wales. The socioeconomic gradient in survival was much smaller than that seen for colorectal cancer patients in the general population, both at 1 year -3.2% (95% CI -7.3 to 1.0%, P=0.14) and at 5 years -1.7% (95% CI -8.3 to 4.9%, P=0.61). Given equal treatment, colorectal cancer survival in England and Wales does not appear to depend on socioeconomic status, suggesting that the socioeconomic gradient in survival in the general population could well be due to health-care system factors. [ABSTRACT FROM AUTHOR]

Background: Despite improvements in the treatment of ovarian cancer, most patients develop recurrent disease within 3 years of diagnosis. There is no agreed second-line treatment at relapse. We assessed paclitaxel plus platinum chemotherapy as such treatment.Methods: In parallel international, multicentre, randomised trials, between January, 1996, and March, 2002, 802 patients with platinum-sensitive ovarian cancer relapsing after 6 months of being treatment-free were enrolled from 119 hospitals in five countries. Patients were randomly assigned paclitaxel plus platinum chemotherapy or conventional platinum-based chemotherapy. Analysis was by intention to treat, except for toxic effects.Findings: With a median follow-up of 42 months, 530 patients have died. Survival curves showed a difference in favour of paclitaxel plus platinum (hazard ratio 0.82 [95% CI 0.69-0.97], p=0.02), corresponding to an absolute difference in 2-year survival of 7% between the paclitaxel and conventional treatment groups (57 vs 50% [95% CI for difference 1-12]), and median survival of 5 months (29 vs 24 months [1-11). 717 patients developed progressive disease or died. The progression-free survival curves show a difference in favour of paclitaxel plus platinum (hazard ratio 0.76 [0.66-0.89], p=0.0004), corresponding to an absolute difference in 1-year progression-free survival of 10% (50 vs 40% [4-15]) and in median progression-free survival of 3 months (13 vs 10 months [1-5]).Interpretation: Paclitaxel plus platinum chemotherapy seems to improve survival and progression-free survival among patients with relapsed platinum-sensitive ovarian cancer compared with conventional platinum-based chemotherapy. [ABSTRACT FROM AUTHOR]

The randomized multicentre trial of continuous hyperfractionated accelerated radiotherapy (CHART) versus conventional radiotherapy in patients with advanced head and neck cancer showed no good evidence of a difference in any of the major clinical outcomes of survival, freedom from metastases, loco-regional control and disease-free survival. Therefore an assessment of the effect of treatment on physical and psychological symptoms is vital to balance the costs and benefits of the two treatments. A total of 615 patients were asked to complete a Rotterdam Symptom Checklist and the Hospital Anxiety and Depression Scale, which cover a variety of physical and psychological symptoms, at a total of ten time points. The data consisted of short-term data (the initial 3 months) and long-term data (1 and 2 years). The short-term data was split into an exploratory data set and a confirmatory data set, and analysed using subject-specific and group-based methods. Differences were only claimed if hypotheses generated in the exploratory data set were confirmed in the confirmatory data set. The long-term data was not split into two data sets and was analysed using a group-based approach. There was evidence of significantly worse symptoms of pain at day 21 in those treated with CHART and significantly worse symptoms of cough and hoarseness at 6 weeks in those treated conventionally. There was also evidence to suggest a higher degree of decreased sexual interest at 1 year and sore muscles at 2 years in those treated with conventional radiotherapy. There is no clear indication that one regimen is superior to the other in terms of 'quality of life', generally the initially more severe reaction in the CHART group being offset by the longer duration of symptoms in the conventionally treated group. [ABSTRACT FROM AUTHOR]