European Journal of Cancer: Highlights of Issue 38:02

Chemoradiotherapy

This Special Issue contains 9 reviews from experts in the field of chemoradiotherapy. Chemoradiotherapy was initially advocated due to the possibility of an independent cell-killing effect both at the level of the primary tumour and metastases. Treatment regimens have the advantage of allowing organ preservation in some cases such as laryngeal cancer or the reduced use of colostomy for anal cancer. However, they are often associated with increased toxicity and data on late effects are not yet available for many studies. Chemoradiotherapy can be administered sequentially, concurrently or in an alternating schedule.

The use of chemotherapy and radiotherapy has been explored in a variety of settings including cancers of the cervix (see Rose and colleagues), head and neck (see Geh and colleagues), anus (see Bartelink and colleagues) and lung (see Novello and colleagues and Turisi and colleagues). Trials exploring combined treatments for these various sites have suggested that concomitant regimens are better in terms of local control and survival (see overview by Bartelink and colleagues). However, we are far from having optimal regimens and ways to increase the efficacy of chemoradiotherapy need to be explored.

Most of the clinical experience is with cisplatin either alone or in combination, but the use of other newer drugs such as the topoisomerase inhibitors or drugs that act as molecular biology response modifiers are under investigation. Furthermore, by understanding the biological basis and mechanisms of interaction, we can begin to optimise the timing of the schedules, doses of radiotherapy and chemotherapy (see Hennequinn and colleagues and Glynne-Jones and colleagues). These mechanisms can be varied and include increased DNA double-strand breaks, inhibition of repair, cell cycle effects and increased apoptosis, to name a few. Hypoxia is a negative prognostic outcome indicator following radiotherapy for many tumour sites. As discussed by Wouters and colleagues, hypoxic-specific therapies are being designed aimed at the unique microenvironment of the tumour such as hypoxic-responsive element (HRE)-directed gene therapy targeted at the hypoxic cell (see Marples and colleagues).

Several of these strategies are now being tested in clinical trials. The use of the monoclonal antibody C225 (Cetuximab) to block EGFR expression, that is often associated with a poor prognosis, has shown promising results in a multicentre phase III trial in advanced head and neck patients. The early data from this trial indicate a high response rate and minimal side-effects. Farnesyl transferase inhibitors are also being explored in clinical trials (in combination with radiotherapy) for head and neck cancer, as preclinical studies showed these inhibitors could increase radiosensitivity.

Chemoradiotherapy has become the 'state of the art' treatment for many common cancers. This needs close collaboration between medical and radiation oncologists specialising in specific tumour types with multidisciplinary collaboration ensuring the optimal management of individual patients. We hope that this Special Issue will contribute to this dialogue by bringing together the clinical experience and research evaluation of this important concept.

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