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DACA, also known as XR5000, is an acridine derivative active against both topoisomerase I and II. In this phase I study, DACA was given as a 3-h intravenous infusion on 3 successive days, repeated every 3 weeks. A total of 41 patients were treated at 11 dose levels between 9 mg m −2 d −1 and the maximum tolerated dose of 800 mg m −2 day −1 . The commonest, and dose-limiting, toxicity was pain in the infusion arm. One patient given DACA through a central venous catheter experienced chest pain with transient electrocardiogram changes, but no evidence of myocardial infarction. At the highest dose levels, several patients also experienced flushing, pain and paraesthesia around the mouth, eyes and nose and a feeling of agitation. Other side-effects, such as nausea and vomiting, myelosuppression, stomatitis and alopecia, were uncommon. There was one minor response but no objective responses. DACA pharmacokinetics were linear and did not differ between days 1 and 3. The pattern of toxicity seen with DACA is unusual and appears related to the mode of delivery. It is possible that higher doses of DACA could be administered using a different schedule of administration. © 1999 Cancer Research Campaign

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Radiotherapy is well tolerated and effective in regional control. However, patients are at risk of early distant relapse, particularly those with ECE or large tumour size. There are currently no useful prognostic markers to differentiate the risk of regional versus distant recurrence, and the optimal treatment paradigm remains undefined. Research on adjuvant systemic therapies and abscopal effects of radiotherapy have shown improved management of distant metastasis; creating an even greater need for effective regional control strategies.