[Show abstract][Hide abstract] ABSTRACT: Both oxaliplatin/capecitabine-based chemoradiation (OXCAP-RT) and carboplatin-paclitaxel based radiation (CarPac-RT) are active regimens in oesophageal adenocarcinoma, but no randomised study has compared their efficacy and toxicity. This randomised phase II "pick a winner" trial will identify the optimum regimen to take forward to a future phase III trial against neo-adjuvant chemotherapy, the current standard in the UK.
Patients with resectable adenocarcinoma of the oesophagus or Siewert Type 1-2 gastro-oesophageal junction (GOJ), ≥T3 and/or ≥ N1 are eligible for the study. Following two cycles of induction OXCAP chemotherapy (oxaliplatin 130 mg/m2 D1, Cape 625 mg/m(2) D1-21, q 3 wk), patients are randomised 1:1 to OXCAP-RT (oxaliplatin 85 mg/m(2) Day 1,15,29; capecitabine 625 mg/m(2) twice daily on days of RT; RT-45 Gy/25 fractions/5 weeks) or CarPac-RT (Carboplatin AUC2 and paclitaxel 50 mg/m2 Day 1,8,15,22,29; RT-45 Gy/25 fractions/5 weeks). Restaging CT/PET-CT is performed 4-6 weeks after CRT, and a two-phase oesophagectomy with two-field lymphadenectomy is performed six to eight weeks after CRT. The primary end-point is pathological complete response rate (pCR) at resection and will include central review. Secondary endpoints include: recruitment rate, toxicity, 30-day surgical morbidity/mortality, resection margin positivity rate and overall survival (median, 3- and 5-yr OS. 76 patients (38/arm) gives 90% power and one-sided type 1 error of 10% if patients on one novel treatment have a response rate of 35% while the second treatment has a response rate of 15%. A detailed RT Quality Assurance (RTQA) programme includes a detailed RT protocol and guidance document, pre-accrual RT workshop, outlining exercise, and central evaluation of contouring and planning. This trial has been funded by Cancer Research UK (C44694/A14614), sponsored by Velindre NHS Trust and conducted through the Wales Cancer Trials Unit at Cardiff University on behalf of the NCRI Upper GI CSG.
Following encouraging results from previous trials, there is an interest in neo-adjuvant chemotherapy and CRT containing regimens for treatment of oesophageal adenocarcinoma. NEOSCOPE will first establish the efficacy, safety and feasibility of two different neo-adjuvant CRT regimens prior to a potential phase III trial.
Eudract No: 2012-000640-10. ClinicalTrials.gov: NCT01843829 .
[Show abstract][Hide abstract] ABSTRACT: Interventional oncology is a rapidly growing sub-speciality that aims to develop new disease-modifying treatment options beyond conventional surgical and oncological therapies in several disease settings. The evidence for interventional oncology success is dominated by single-arm studies reporting technical success or clinical efficacy. These studies have successfully resulted in the development of new techniques, but are not sufficient to change clinical practice uniformly across health-care systems. This Review discusses why clinical investigators must incorporate measures of cost-effectiveness and patient-reported outcomes into large-scale studies currently being designed to provide robust evidence for changing clinical practice. In particular, interventional oncology trials could be designed to show that certain treatments may be as effective as the current standard of care, but with significantly less morbidity and with better outcomes for patients with cancer. Innovative trial design and awareness of the challenges from interventional studies in other fields of medicine and surgery are also discussed to demonstrate how this new speciality can make progress. Registry-based models are emerging as an alternative means of deriving cohort data and can be used in parallel with local or national commissioning of new services.
No preview · Article · Dec 2014 · Nature Reviews Clinical Oncology
[Show abstract][Hide abstract] ABSTRACT: Colorectal cancer (CRC) is the second most common malignancy in Europe and a leading cause of cancer-related death. Almost 50% of patients with CRC develop liver metastases, which heralds a poor prognosis unless metastases can be downsized to surgical resection or ablation. The FOXFIRE trial examines the hypothesis that combining radiosensitising chemotherapy (OxMdG: oxaliplatin, 5-fluorouracil and folic acid) with Selective Internal Radiation Therapy (SIRT or radioembolisation) using yttrium-90 resin microspheres (SIR-Spheres®; Sirtex Medical Limited, North Sydney, Australia) as a first-line treatment for liver-dominant metastatic CRC will improve clinical outcomes when compared to OxMdG chemotherapy alone.
FOXFIRE is an open-label, multicentre, randomised controlled trial of OxMdG with or without the addition of SIRT (1:1 randomisation). Eligible adult patients have histologically confirmed colorectal adenocarcinoma, liver metastases measurable on computed tomography scan and untreatable by either surgical resection or local ablation, and they may have limited extra-hepatic disease, defined as ≤5 nodules in the lung and/or one other metastatic site which is amenable to future definitive treatment. Eligible patients may have received adjuvant chemotherapy following resection of the primary tumour, but are not permitted to have previously received chemotherapy for metastatic disease, and must have a life expectancy of ≥3 months and a WHO performance status of 0–1. The primary outcome is overall survival. Secondary outcomes include progression free survival (PFS), liver-specific PFS, patient-reported outcomes, safety, response rate, resection rate and cost-effectiveness. FOXFIRE shares a combined statistical analysis plan with an international sister trial called SIRFLOX.
This trial is establishing a network of SIRT centres and ‘feeder’ chemotherapy-only centres to standardise the delivery of SIRT across the whole of the UK and to provide greater equity of access to this highly specialised liver-directed therapy. The FOXFIRE trial will establish the potential role of adding SIRT to first-line chemotherapy for unresectable liver metastatic colorectal cancer, and the impact on current treatment paradigms for metastatic CRC.
[Show abstract][Hide abstract] ABSTRACT: Neoadjuvant chemoradiotherapy for locally advanced rectal cancer has been shown to decrease rates of local recurrence and more than double the rate of sphincter-preserving surgery. There is now compelling evidence that pathological complete response is an independent predictor of likelihood of local recurrence, distal metastases, disease-free and overall survival in locally advanced rectal cancer following neoadjuvant chemoradiotherapy. Pathological regression grading can therefore guide clinical decisions about salvage surgical strategies, adjuvant therapy and long-term surveillance. No universally recognised regression grading system currently exists for pathologists presented with resected tumour specimens following neoadjuvant chemoradiotherapy. The purpose of this review is to highlight the relevance of accurate tumour regression grading in achieving optimal clinical care for patients with rectal cancer.
No preview · Article · Jun 2012 · Journal of clinical pathology