P-0249 Use of Dose-Modified Capiri in Metastatic Colorectal Cancer Reduces Toxicity Whilst Maintaining Efficacy

Abstract

ABSTRACT Introduction The combination of irinotecan and capecitabine (CAPIRI) is effective in the treatment of metastatic colorectal cancer. However, studies using standard dose CAPIRI (irinotecan 225-250mg/m2 day 1 and capecitabine 1000mg/m2 bd days 1-14) have demonstrated that treatment may be limited by unacceptable levels of toxicity, in particular grade 3/4 diarrhoea. Subsequent studies investigating the effect of dose-modified CAPIRI on efficacy and toxicity have suggested that reducing the doses of both drugs results in a more favourable toxicity profile. However the majority of these modified-dose studies involved CAPIRI in combination with other agents such as bevacizumab, celecoxib and cetuximab, making it difficult to draw conclusions regarding the efficacy and side-effect profile of dose-modified CAPIRI alone. This study investigated the efficacy and toxicity of dose-modified CAPIRI in 78 patients with metastatic colorectal cancer at a single UK cancer centre. Methods 78 patients with metastatic colorectal cancer were treated with CAPIRI in either the 1st line (n=32), 2nd line (n=44) or 3rd line (n=2) metastatic setting. A retrospective analysis of patient and treatment data was conducted using information from case notes, imaging and pathology reports. All patients received irinotecan 140-200mg/m2 day 1 and capecitabine 625-800mg/m2 bd in two-weekly (n=55) or three-weekly (n=23) cycles. Information from imaging reports, MDT meeting documentation and clinic letters was used to assess radiological response to treatment. Toxicity was graded according to the National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 2.0. Results The objective response rate (ORR) (complete and partial responses combined) was 32%. Stable disease (SD) was achieved in a further 21%, giving a disease control rate (ORR+SD) of 53%. ORR was highest in patients receiving CAPIRI 1st line in the metastatic setting, with 47% achieving at least a partial response. Median progression-free survival (PFS) was 8.3 months (95% CI 6.8 – 9.8 months). In the 1st line setting, median PFS was 9.6 months (95% CI 6.8–12.4 months). In the 2nd line setting, median PFS was 6.6 months (95% CI 2.6–10.7 months). There were no grade 4 toxicities observed. The most common grade 3 toxicities observed were neutropenia (20%) and diarrhoea (14%). 15 patients discontinued treatment due to toxicity. Conclusion This study demonstrates that the use of dose-modified CAPIRI to treat metastatic colorectal cancer reduces toxicity whilst maintaining efficacy. ORR was comparable to that achieved in the majority of large phase II studies and exceeded that of the largest phase III study to date. Patients treated with dose-modified CAPIRI achieved PFS comparable to that seen in studies using higher doses with a significant reduction in toxicity (see table). The incidence of grade 3 diarrhoea was significantly lower than that seen in all phase III studies using CAPIRI to date. Rates of grade 3 neutropenia fell within the range of those seen in previous phase II and III studies. These findings suggest that the use of a dose-modified CAPIRI regime may confer both clinical and cost benefits in this population.