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O27 - Clinical Trials and Practice (ID 142)
- Event: WCLC 2013
- Type: Oral Abstract Session
- Track: Other Topics
- Presentations: 1
- Moderators:J.S. Lee, J. Bishop
- Coordinates: 10/29/2013, 16:15 - 17:45, Bayside Auditorium A, Level 1
O27.02 - Preliminary results from the FRAGMATIC trial: A randomised Phase III clinical trial investigating the effect of FRAGMin® Added to standard Therapy In patients with lung Cancer. (ID 1799)
16:15 - 17:45 | Author(s): R. Cowles
Venous thromboembolism (VTE) is common in lung cancer patients and the incidence is increased by treatments including radiotherapy, surgery and chemotherapy. Research suggests a survival benefit in cancer patients receiving long term low moecular weight heparin (LMWH). LMWH may also have antimetastatic effects through the inhibition of P-selectin. This trial was developed to investigate whether or not adding LMWH to standard treatment increases overall survival. The study is funded by a research grant from Cancer Research UK (C13275/A5323) and free drug and an educational grant from Pfizer. The trial is sponsored by Velindre NHS Trust, and coordinated by the Wales Cancer Trials Unit, Cardiff, UK.
An open label, multi-centre, Phase III randomised controlled trial in patients with lung cancer comparing anticancer treatment according to local practice plus dalteparin (Fragmin®), with anticancer treatment alone. Eligible patients had a histopathological or cytological diagnosis of primary bronchial carcinoma (SCLC or NSCLC) within the previous 7 weeks, performance status 0, 1, 2 or 3 and were willing and able to inject daily subcutaneous injection. The dalteparin was given as a daily 5,000 IU subcutaneous injection for 24 weeks. The primary outcome measure is overall survival and the secondary outcome measures include toxicity, VTE-free survival, metastasis-free survival, quality of life, and cost utility. To detect an advantage of 5% in overall survival at 1 year (to 30%) a total of 2200 patients were required (1100 in each arm).
2202 patients were enrolled and randomised in 4 years. The two groups were well balanced for key variables. 60% were men; the median age was 65 years; 82% had NSCLC (5% Stages I and II, 38% Stage III, 57% Stage IV) and 18% SCLC (63% Extensive Disease); 85% had WHO PS 0 or 1; 95% received chemotherapy as first treatment. 56% of those in the dalteparin arm received at least 90 of the 168 planned injections. By 1/8/2013 there had been 1891 deaths recorded and, on advice from the Independent Data Monitoring Committee, the primary results have been released. There was no significant difference in overall survival (HR 0.97; 95% CI 0.89-1.06) nor in metastasis-free survival. Exploratory subgroup analyses do not suggest a significant survival advantage in any subgroup. Dalteparin use was not associated with a significant increase in major bleeding complications. There were 78 (7.1%) confirmed VTEs in the control group and 47 (4.1%) in the treatment group.
This large RCT which recruited mainly good PS lung cancer patients having chemotherapy, has confirmed that prophylactic dalteparin reduces the risk of VTE events without a significant increase in major bleeding. The baseline VTE risk of 7% and relative risk reduction of 40% are consistent with previous studies. There was no significant difference in overall survival. These results do not support a policy of routine prophylactic anticoagulation of all lung cancer patients undergoing chemotherapy.
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P3.08 - Poster Session 3 - Radiotherapy (ID 199)
- Event: WCLC 2013
- Type: Poster Session
- Track: Radiation Oncology + Radiotherapy
- Presentations: 1
- Coordinates: 10/30/2013, 09:30 - 16:30, Exhibit Hall, Ground Level
P3.08-012 - I-START Trial: A UK phase I/II trial of isotoxic accelerated radiotherapy in locally advanced non-small cell lung cancer (ID 1575)
09:30 - 16:30 | Author(s): R. Cowles
Approximately 35,000 people die from lung cancer each year in the UK, the majority from non-small cell lung cancer (NSCLC). Patients with locally advanced (LA) NSCLC are often not suitable for chemotherapy or combined chemo-radiotherapy treatment because of patient or tumour factors. In these cases radical radiotherapy alone is used. Increased radiation dose may improve both local tumour control and survival. The radiotherapy dose is limited by surrounding organs, which include the lungs, heart, spinal cord and oesophagus. The maximum radiotherapy dose that can safely be delivered to the oesophagus is not known. The I-START trial was therefore developed, on behalf of the UK National Cancer Research Institute Lung Clinical Studies Group, to establish oesophageal radiation dose limits and to investigate the feasibility and effectiveness of a novel approach to dose escalation in LA-NSCLC. The study is funded by Cancer Research UK (C25518/A11535), sponsored by Velindre NHS Trust and coordinated by the Wales Cancer Trials Unit.
Patients with histologically or cytologically confirmed stage II to IIIb NSCLC, suitable for radical radiotherapy, are eligible for the trial. Enrolled patients will receive 20 fractions of radiotherapy over 4 weeks. The trial is split into two phases: Phase I: To establish the maximum tolerated (MTD) dose of radiotherapy to the oesophagus in patients where the oesophagus overlaps with the planning target volume (PTV). Phase I patients will be split into 2 groups depending on the length of the oesophagus lying within the PTV (Group 1A is where the overlap ≤6.5cm and Group 1B is where the overlap >6.5cm). Cohorts of 6 or 12 patients are recruited to both groups at sequentially increasing dose levels (58, 61, 63, 65Gy). Progression to the next oesophageal dose level will depend on the number of patients in a cohort with grade 3 or 4 acute oesophagitis, or other grade 3 or 4 toxicity, occurring up to 2 months after radiotherapy. Once the MTD to the oesophagus is established for each group, all participants will follow the Phase II protocol with the determined oesophageal dose limit. Phase II: Patients will receive a maximum of 65Gy in 20 fractions and the dose prescribed will be the highest dose achievable without exceeding defined safe dose limits for organs at risk. Where the oesophagus does not overlap with the PTV, patients can immediately be treated in Phase II, whereas patients whose oesophagus overlaps with the PTV can only be entered into Phase II once Phase I is complete, i.e. the MTD to the oesophagus has been established. The primary outcome of Phase II is the toxicity rate (grade 3 or 4) at 3 months. The I-START trial will determine whether this novel method of increasing the radiotherapy dose in patients with NSCLC patients is tolerable, safe and effective. If the results are positive, then this new treatment may be compared against the best currently available standard treatment in a future larger randomised (Phase III) trial.