Early analysis of toxicity and surgery in patients treated with cetuximab single agent followed by 5-fu, cetuximab and pelvic radiotherapy as neo-adjuvant treatment for operable, locally advanced rectal cancer (rc)

Abstract

14531 Background: Pre-operative chemo-radiotherapy in locally advanced RC has been used to improve local control and to facilitate sphincter-sparing surgery for distal tumors. Cetuximab, an anti EGFR monoclonal antibody, has proved efficacy in advanced colorectal cancer. Methods: Study design provided: 1) tumor biopsy to confirm diagnosis and to measure tumor biomarkers (EGFR, TS, p53, MAP kinase, Ki 67, p21, bcl-2; immunological cell profile at the tumor level: CD45RO, CD68, CD56 CD4+/CD25+, CD31, HLA-A, -B and -C), 2) Cetuximab single agent (400 mg/sqm loading dose, then 250 mg/sqm weekly) for 3 doses, 3) a second biopsy to evaluate tumor biomarkers, 4) Cetuximab 250 mg/sqm weekly plus 5FU (225 mg/sqm in continuous infusion) concomitantly with RT (50 Gy), 5) surgery. Tumor biomarkers are measured again on tumor specimen in non pCR patients (pts). 66 pts with resectable uT3/uT4 N0/+ RC will enter the study. Primary aim is: toxicity and activity (pathologic complete response). Secondary aim is: evaluation of biological parameters, rates of sphincter sparing surgery and disease free survival. Results: Up to now 29 pts are valuable for toxicity (M/F= 22/5; median age: 61; range: 35–74). Ultrasound staging at diagnosis is: uT3N0: 7; uT3N1: 20; uT4N1: 2. Four pts (14%) withdrew neo-adjuvant treatment after 1 administration of Cetuximab: 2 for hypersensitivity reactions (1 G3; 1 G4), 1 for progression and 1 for purulent arthritis. Twenty-two pts (75%) presented acne-like rash; treatment with Cetuximab was interrupted or reduced in 4 pts (14%): in 2 for acne-like rash grade 3 (NCI-CTC) and in 2 pts for refuse. Grade 1–2 gastro-intestinal toxicity (unrelated to Cetuximab) was observed in 13 pts (proctitis: 4; diarrhoea: 9); in 1 case: diarrhoea G4. Twenty pts are valuable for surgery: 18 pts (90%) underwent conservative surgery. Two pts (10%) experienced post-surgical complications: 1 anastomotic fistula and 1 colonic necrosis. Conclusions: Pre-operative treatment with 5FU, Cetuximab and pelvic RT is well tolerated and does not increase surgical complication rate. An update on efficacy data and biological markers evaluation will be presented at the meeting. No significant financial relationships to disclose.