A phase II study of cetuximab, capecitabine and radiotherapy in neoadjuvant treatment of patients with locally advanced resectable rectal cancer.

BACKGROUND: Neoadjuvant chemoradiotherapy (CRT) reduces local tumor recurrence in locally advanced rectal cancer (LARC). This phase II study assessed neoadjuvant cetuximab with capecitabine-based CRT in LARC.

METHODS: Patients with stage II/III LARC received capecitabine 1250 mg/m(2) twice daily for 2 weeks followed by intravenous cetuximab 400 mg/m(2) at week 3, then weekly intravenous 250 mg/m(2) cetuximab plus CRT including capecitabine 825 mg/m(2) twice daily (including weekends during radiotherapy) with radiotherapy of 45 Gy (25 x 1.8 Gy), 5 days a week for 5 weeks. Total mesorectal excision was scheduled 4-6 weeks following completion of CRT. The primary endpoint was pathological complete response (pCR).

RESULTS: Thirty-seven patients were eligible for safety and efficacy. TMN staging at baseline was: T4N2, 11%; T3N2, 40%; T2N2, 3%; T3N1, 35%; T2N1, 3% and T3N0 8%. The most common adverse events included, grade 1/2 acneiform skin rash (86%), and grade 3 radiodermatitis, (16%), diarrhea (11%) and hypersensitivity (5%). pCR was achieved in 3 patients (8%). Overall-, T- and N-downstaging rates were 73%, 57% and 81% respectively. Total sphincter preservation rate was 76%, and 53% in 17 patients whose tumors were located within 5 cm from the anal verge. Non-fatal perioperative complications occurred in 13 patients (35%) with delayed wound healing occurring in 6 patients (16%). One death was recorded due to sepsis following colonic necrosis.

CONCLUSION: Neoadjuvant cetuximab with capecitabine-based CRT is tolerable in patients with resectable LARC. Whilst the pCR rate was similar to recent reports, a high pathological downstaging rate was achieved.