Results of a phase I study to determine the maximum tolerated dose of capecitabine when given concurrently with radical radiotherapy in the treatment of squamous cell carcinoma of the head and neck.

Capecitabine is preferentially converted to 5-fluorouracil within tumours, exploiting the higher levels of thymidine phosphorylase (TP) found in areas of poor perfusion and hypoxia. In addition radiation leads to up regulation of TP expression. To exploit these advantages of capecitabine as a synchronous chemoradiotherapy agent patients with advanced squamous cell carcinoma of the head and neck were recruited into a phase I non-randomised dose finding study. Capecitabine was given twice daily, 7 days a week at a dose starting at 350 mg/m(2) bid. Radiotherapy using a beam directed technique was prescribed to 55 Gy in 20 fractions over 4 weeks. A total of 24 patients were treated. Dose-limiting toxicity (grade IV mucositis) was reached at a capecitabine dose of 550 mg/m(2) bid. Radiotherapy was completed without delay in all cases. There was no systemic drug related toxicity. Capecitabine offers the prospect of an orally administered drug for use synchronously with radiotherapy, which in doses up to 500 mg/m(2) bid is well tolerated.

Routine use of continuous, hyperfractionated, accelerated radiotherapy for non-small-cell lung cancer: a five-center experience.

PURPOSE: To report the results from continuous, hyperfractionated, accelerated radiotherapy (CHART) used as the standard fractionation for radical RT in the management of non-small cell lung cancer (NSCLC) in five United Kingdom centers. METHODS AND MATERIALS: In 2005, the CHART consortium identified six U.K. centers that had continued to use CHART after the publication of the CHART study in 1997. All centers had been using CHART for >5 years and agreed to use a common database to audit their results. Patients treated with CHART between 1998 and December 2003 were identified to allow a minimum of 2 years of follow-up. Patient demographics, tumor characteristics, treatment details, and survival were recorded retrospectively. Five centers completed the data collection. RESULTS: A total of 583 patients who had received CHART were identified. Of these patients, 69% were male, with a median age of 68 years (range, 31-89); 83% had performance status 0 or 1; and 43% had Stage I or II disease. Of the 583 patients, 99% received the prescribed dose. In only 4 patients was any Grade 4-5 toxicity documented. The median survival from the start of RT was 16.2 months, and the 2-year survival rate of 34% was comparable to that reported in the original study. CONCLUSION: The results of this unselected series have confirmed that CHART is deliverable in routine clinical practice, with low levels of toxicity. Importantly, this series has demonstrated that the results of CHART reported from the randomized trial can be reproduced in routine clinical practice.

Improved treatment and survival for lung cancer patients in South-East Scotland.

INTRODUCTION: Lung cancer survival in Scotland has historically been poor but many changes to the lung cancer services have been introduced and this study was conducted to investigate the impact of these changes on treatment and survival. METHODS: Data obtained from the Scottish Cancer Registry, South-East Scotland Cancer Network audit and Edinburgh Cancer Centre database were used to conduct a comparison of the management and outcomes of lung cancer patients from South-East Scotland diagnosed in 1995 and in 2002. RESULTS: Data on 971 patients diagnosed in 2002 and 927 in 1995 were analyzed and demonstrated that though the use of treatment overall had not changed (62% in 2002 versus 63% in 1995) the use of potentially curative radiotherapy (15 versus 5% chi p < 0.001) and chemotherapy for non-small cell lung cancer (18 versus 7% chi p < 0.001) had increased, but not resection rates (11 versus 10%). The use of palliative radiotherapy declined (38% versus 31% chi p < 0.001). Patients diagnosed in 2002 had an adjusted hazard of death of 0.7 (95% confidence interval, 0.6-0.8) compared with 1995, with median survival from date of diagnosis of 5.2 versus 4.1 month and 2 year overall survival 15 versus 11% (log rank p = 0.004). Localized disease and younger age were also associated with a reduced hazard of death. CONCLUSIONS: Patients diagnosed with lung cancer in Scotland in 2002 had a reduced hazard of death and improved survival compared with 1995. It is hypothesized that this was due in part to improvements in service organization and increased use of treatments likely to increase survival.