FRAGMATIC: a randomised phase III clinical trial investigating the effect of fragmin added to standard therapy in patients with lung cancer.

BACKGROUND: Venous thromboembolism (VTE) occurs when blood clots in the leg, pelvic or other deep vein (deep vein thrombosis) with or without transport of the thrombus into the pulmonary arterial circulation (pulmonary embolus). VTE is common in patients with cancer and is increased by surgery, chemotherapy, radiotherapy and disease progression. Low molecular weight heparin (LMWH) is routinely used to treat VTE and some evidence suggests that LMWH may also have an anticancer effect, by reduction in the incidence of metastases. The FRAGMATIC trial will assess the effect of adding dalteparin (FRAGMIN), a type of LMWH, to standard treatment for patients with lung cancer. METHODS/DESIGN: The study design is a randomised multicentre phase III trial comparing standard treatment and standard treatment plus daily LMWH for 24 weeks in patients with lung cancer. Patients eligible for this study must have histopathological or cytological diagnosis of primary bronchial carcinoma (small cell or non-small cell) within 6 weeks of randomisation, be 18 or older, and must be willing and able to self-administer 5000 IU dalteparin by daily subcutaneous injection or have it administered to themselves or by a carer for 24 weeks. A total of 2200 patients will be recruited from all over the UK over a 3 year period and followed up for a minimum of 1 year after randomisation. Patients will be randomised to one of the two treatment groups in a 1:1 ratio, standard treatment or standard treatment plus dalteparin. The primary outcome measure of the trial is overall survival. The secondary outcome measures include venous thrombotic event (VTE) free survival, serious adverse events (SAEs), metastasis-free survival, toxicity, quality of life (QoL), levels of breathlessness, anxiety and depression, cost effectiveness and cost utility. TRIAL REGISTRATION: Current Controlled Trials ISRCTN80812769.

Lung cancer management in limited resource settings: guidelines for appropriate good care.

Lung cancer is a major cause of cancer death worldwide and is becoming an increasing problem in developing countries. It is important that, in countries where health care resources are limited, these resources are used most effectively and cost-effectively. The authors, with the support of the International Atomic Energy Agency, drew on existing evidence-based clinical guidelines, published systematic reviews and meta-analyses, as well as recent research publications, to summarise the current evidence and to make broad recommendations on the non-surgical treatment of patients with lung cancer. Tables were constructed which summarise the different treatment options for specific groups of patients, the increase in resource use for and the likely additional clinical benefit from each option. These tables can be used to assess the cost-effectiveness and appropriateness of different interventions in a particular health care system and to develop local clinical guidelines.

Prophylactic cranial irradiation for preventing brain metastases in patients undergoing radical treatment for non-small-cell lung cancer: a Cochrane Review.

PURPOSE: To investigate whether prophylactic cranial irradiation (PCI) has a role in the management of patients with non-small-cell lung cancer (NSCLC) treated with curative intent. METHODS AND MATERIALS: A search strategy was designed to identify randomized controlled trials (RCTs) comparing PCI with no PCI in NSCLC patients treated with curative intent. The electronic databases MEDLINE, EMBASE, LILACS, and Cancerlit were searched, along with relevant journals, books, and review articles to identify potentially eligible trials. Four RCTs were identified and reviewed. A total of 951 patients were randomized in these RCTs, of whom 833 were evaluable and reported. Forty-two patients with small-cell lung cancer were excluded, leaving 791 patients in total. Because of the small patient numbers and trial heterogeneity, no meta-analysis was attempted. RESULTS: Prophylactic cranial irradiation did significantly reduce the incidence of brain metastases in three trials. No trial reported a survival advantage with PCI over observation. Toxicity data were poorly collected and no quality of life assessments were carried out in any trial. CONCLUSION: Prophylactic cranial irradiation may reduce the incidence of brain metastases, but there is no evidence of a survival benefit. It was not possible to evaluate whether any radiotherapy regimen is superior, and the effect of PCI on quality of life is not known. There is insufficient evidence to support the use of PCI in clinical practice. Where possible, patients should be offered entry into a clinical trial.

CT-planned accelerated hypofractionated radiotherapy in the radical treatment of non-small cell lung cancer.

Surgery is the standard treatment for stage I, II and certain stage IIIA non-small cell lung cancers (NSCLC). A proportion of patients with technically operable NSCLC do not undergo surgery because of significant co-morbidity or refusal, and radical radiotherapy may cure some of these patients. Between April 1997 and March 2000, 135 consecutive patients with stage I-IIIB NSCLC were treated with CT-planned accelerated hypofractionated radical radiotherapy to a dose of 50-55Gy in 15-20 fractions over 3-4 weeks at a single centre. The 2-year overall and cause-specific survival for all patients was 44.4% (95% CI = 36.8, 53.7) and 47.8% (95% CI = 39.9, 57.3) respectively. Overall median survival was 21 months (95% 18, 28). There were no reports of severe acute or late treatment-related toxicities. These results compare favourably with previously published studies on radical radiotherapy in NSCLC, suggesting this may be an effective and safe technique.