Simultaneous neoadjuvant radiochemotherapy with capecitabine and oxaliplatin for locally advanced rectal cancer. Treatment outcome outside clinical trials.

BACKGROUND: Phase II trials of neoadjuvant treatment in UICC-TNM stage II and III rectal cancer with capecitabine and oxaliplatin demonstrated favourable rates on tumour regression with acceptable toxicity. PATIENTS AND METHODS: Retrospective evaluation of 34 patients treated from 2005-2008 outside clinical trials (CTR) with neoadjuvant irradiation (45-50.4 Gy) and simultaneous capecitabine 825 mg/m(2) b.i.d. on days 1-14 and 22-35 and oxaliplatin 50 mg/m(2) on days 1, 8, 22 and 29 (CAPOX). Twenty-six (77%) patients received one or two courses of capecitabine 1,000 mg/m(2) b.i.d. on days 1-14 and oxaliplatin 130 mg/m(2) on day 1 (XELOX) prior to simultaneous chemoradiotherapy.
RESULTS: UICC-TNM stage regression was observed in 60% (n = 20). Dworak's regression grades 3 and 4 were achieved in 18.2% (n = 6) and 15.1% (n = 5) of the patients. Sphincter-preserving surgery was performed in 53% (n = 8) of patients with a tumour of the lower rectum. Within the mean observation of 24 months, none of the patients relapsed locally, 1 patient had progressive disease and 5 patients (15%) relapsed distantly. Toxicity of grade 3 and 4 was mainly diarrhoea 18% (n = 6) and perianal pain 9% (n = 3). Nevertheless, severe cardiac events (n = 2), severe electrolyte disturbances (n = 2), and syncopes (n = 2) were observed as well.
CONCLUSION: Treatment efficacy and common toxicity are similar to the reports of phase I/II trials. However, several severe adverse events were observed in our cohort study. The predisposing factors for these events have yet to be studied and may have implications for the selection of patients outside CTR.