Intensified irinotecan-based neoadjuvant chemoradiotherapy in rectal cancer: four consecutive designed studies to minimize acute toxicity and to optimize efficacy measured by pathologic complete response.

BACKGROUND: The objective of the present study was to analyse toxicity and efficacy of irinotecan-based neoadjuvant chemoradiotherapy by the help of four consecutively planed and prospectively performed phase II studies. PATIENTS AND METHODS: Patients with locally advanced rectal cancer received radiotherapy and concurrently chemotherapy consisting 5-Fu/capecitabine in a continuous or intermittent application and irinotecan in two different total doses (240 vs. 200 mg/m(2)).
RESULTS: Diarrhea CTC grade III was seen in 35% in continuous application of 5-Fu/capecitabine versus 12.5% in intermittent application (p= 0,008). Complete response according to the irinotecan dose during chemoradiotherapy (240 mg/m(2) vs. 200 mg/m(2)) was 24% and 0%.
CONCLUSIONS: Chemoradiotherapy of the last phase II study with intermittent capecitabine (1500 mg/m(2)/day, delivered on days 1-14 and 22-35) and irinotecan (4 x 60 mg/m(2)) concurrently to radiotherapy is a safe treatment with low toxicity and high efficacy.