527P - A Phase I/II Study of Bi-Weekly Xeliri with Capecitabine 1,000 Mg/M2 Twice Daily and Irinotecan 180 Mg/M2 Plus Bevacizumab(Bv) for Patient with Metastatic Colorectal Cancer As Second-Line Chemotherapy (Bixer Study)

Abstract

ABSTRACT Aim: Tri-weekly XELIRI is not completely regarded as a valid substitute for FOLFIRI in mCRC because of the potential for greater toxicity. Reduced dose tri-weekly XELIRI is officially recommended recently. This time, we conducted a PI/II study to assess bi-weekly XELIRI plus BV in efficacy and safety as second-line chemotherapy in mCRC. Methods: Patients with prior chemotherapy including oxaliplatin and BV for mCRC, wild or hetero type of UGT1A1 *6*28 were eligible for this study. Treatment comprised capecitabine 1,000 mg/m2 twice daily from the evening of day 1 to the morning of day 8, intravenous irinotecan on day 1, and BV 5mg/kg on day 1 every two weeks. PI study was composed of two steps (irinotecan 150 and 180 mg/m2), and dose limiting toxicity was assessed during the first treatment cycle. The primary endpoint of PII study was progression-free survival (PFS). Results: Recommended dose of irinotecan was determined as 180mg/m2 in PI study. Between Nov 2010 and Aug 2013, 44 patients were enrolled in PII study. Characteristics of patients were as follows (N = 44): median age, 60 yrs (range 32-80 yrs); male/female, 21/23; ECOG PS0, 86.4%; colon/rectum, 23/21; UGT1A1 wild/hetero type, 29/15; and 1st chemo regimen FOLFOX/XELOX, 18/26. The median number of treatment cycles was 10.5. Median PFS was 6.8 months (95%CI, 5.3-8.2 months), and the primary endpoint was met. Median overall survival (OS) was 18.3 months (95%CI, 13.4 - 23.1 months). Response rate was 22.7% (95%CI, 9.8-35.6%). No significant differences in PFS or OS occurred in UGT1A1 status and 1st chemo regimen. Grade 3 or greater adverse events observed were: neutropenia in six, diarrhea in five, nausea in four, anorexia in one, vomiting in one, stomatitis in one, fatigue in one, hand-foot skin reaction in one, hypertension in one, and interstitial pneumonia in one. There were no other severe adverse events and treatment related deaths. Conclusions: In mCRC patients with wild or hetero of UGT1A1*6*28 genotype, biweekly XELIRI + BV is effective and feasible as 2nd line chemotherapy. Bi-weekly XELIRI + BV could be a valid substitute for FOLFIRI + BV in mCRC. Disclosure: All authors have declared no conflicts of interest.