Reply 1: Call for NICE to review urgently their guidance concerning first-line chemotherapy for metastatic colorectal cancer

Reply 1: Call for NICE to review urgently their guidance concerning first-line chemotherapy for metastatic colorectal cancer

example comparing infusional 5FU/FA+oxaliplatin with bolus 5FU/FA+irinotecan. As NICE has now approved irinotecan as second-line therapy, there is a concern that in FOCUS the crossover for patients will be asymmetric. Patients initially having oxaliplatin could expect to crossover (i.e. receive irinotecan as salvage therapy), whereas those initially on irinotecan would not be able to crossover to oxaliplatin, as it is not licensed or approved in this indication. To address this situation the Trial Management Group (TMG) has suggested that, in those patients fit enough to receive it, a planned crossover treatment be designed. The TSC approved this request at their meeting on 19th June, and this will be implemented as soon as possible. This will ensure that every patient entering FOCUS will potentially have access to irinotecan and oxaliplatin at some point.
The TSC, DMEC and TMG believe that FOCUS remains a key trial despite the studies quoted in your editorial. We support its continued accrual, and encourage existing participants and new centres to enter patients. Only in this way can we clarify the use and sequencing of combination chemotherapy as quickly as possible.  In our editorial 'Why hasn't the National Institute been NICE to patients with colorectal cancer', we highlighted the disparity of treatment in England and Wales compared to other industrialised countries, particularly with respect to the poor 5-year survival figures. Our concerns focused on the conclusions reached by the NICE panel in the face of two prospective, randomised trials involving more than 1000 patients showing a survival advantage in *Correspondence: Dr M Saunders, E-mail: mark.saunders@christie-tr.nwest.nhs.uk favour of first-line irinotecan-based therapy (Douillard et al, 2000;Saltz et al, 2000).

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We only referred to the MRC CRO8 (FOCUS) study since the NICE panel recommended entering patients into this trial and were planning to review their guidance when the results from this study are available. We never questioned the ethical validity of the FOCUS study. We simply pointed out that NICE seem to have linked their guidance very closely to this study and feel that they have frankly misinterpreted the many positive studies from here and abroad. NICE also failed to appreciate that patients who were randomised into the two oxaliplatin arms were unable to receive irinotecan at any point, even though they supported second-line use of this drug. We were not questioning the FOCUS study; we simply alluded to this disparity created by NICE. Since our editorial was published, the FOCUS study has, in our opinion, quite rightly added a third-tier of treatment, so allowing all patients to receive both oxaliplatin and irinotecan at some point.
However, according to NICE recommendations, patients who prefer not to be entered into this study should only receive 5-Fluorouracil and folinic acid (5FU/FA) 'up-front', unless they fall into the very small group of patients that have potentially operable liver metastases.
With the widespread availability of the internet and because we need to provide enough information to allow patients to give informed consent, they are quite rightly questioning the NICE guidance in a similar manner to the 28 colorectal oncologists who wrote to the Daily Telegraph in June. Patients are also rightly concerned that the NICE guidance was influenced too much by government funding constraints rather than clinical-effectiveness. We would strongly urge NICE to consider a fresh review before 2005, based on both the convincing existing data (Douillard et al, 2000;Saltz et al, 2000) and the rapidly emerging new data using all three drugs -planned or unplanned (Tournigand et al, 2001;Goldberg et al, 2002).