FOLFIRI-cetuximab: A multicenter phase II proof-of-concept study of a tailored triple combination therapy for safe dose intensification.

e14539 Background: A multicenter phase II trial explored individual 3-drug simultaneous tailoringfor advanced colorectal cancer patients treated with FOLFIRI-Cetuximab regimen using pharmacogenetics and PK-monitoring approaches. Methods: Patients were stratified by their pharmacogenetic/phenotypic status. CPT11 standard dose (180mg/m2) was adjusted per UGT1A1 mutational status. Conventional initial 5-FU dose (2400mg/m2) was adapted according to DPD activity screening (5-FUODPMTox) then dose optimization was PK-guided (5-FUODPMProtocol). Cetuximab PK was performed but dosage remained unchanged. Results: 104 patients were enrolled (18% first line, 82% second line). Mean CPT11 dose at 3 months were: 256±50 mg/ m2 for 6/6 (58), 184±53 mg/ m2 for 6/7 (38) and 127±14 mg/ m2 for 7/7 (8) patients. Initial 5-FU dose was reduced (>20%) for 5.8% of patients but mean 5-FU dose at 3 months was 2580 ±480 mg/ m2 (722 to 4117mg/m2). No grade 4 diarrheas, grade 4 neutropenias in 5.2% of 6/6 patients, 7.9% of 6/7 patients,...