A phase II study of capecitabine, oxaliplatin and irinotecan (XELOXIRI) as salvage therapy in patients with refractory metastatic colorectal cancer.

Abstract

e15049 Background: Advanced colorectal cancer (CRC) refractory to oxaliplatin, irinotecan, and fluoropyrimidines is associated with poor prognosis. The triplet combination of 5-fluorouracil, oxaliplatin, and irinotecan has shown efficacy and tolerability in treatment-naive disease. We investigated the efficacy and tolerability of salvage capecitabine, oxaliplatin and irinotecan (Xeloxiri) in patients who progressed on standard chemotherapy. Methods: This prospective phase 2 study with a primary endpoint of overall response rate (ORR) recruited patients with advanced CRC that have progressed on standard chemotherapy containing fluoropyrimidines, oxaliplatin, and irinotecan either as monotherapy or doublets. Prior use of anti-VEGF, and anti-EGFR agents were allowed. Patients received capecitabine 1250mg/m2 twice daily on day 1-7, oxaliplatin 85mg/m2 and irinotecan 165mg/m2 on day 1 every 2 weeks until disease progression or intolerable toxicity. Secondary endpoints were progression free survival (PFS) and overall survival (OS). Results: Between July 2011 and May 2016, we recruited 32 patients. Median age was 57 and the median number of treatment cycles was 6. 16 patients (50%) were K-RAS wild-type (WT), of which 6 were also N-RAS WT. The ORR was 25% and the clinical benefit rate was 56%. 87.5% of patient received targeted therapy prior to study entry. 34% of patients had > 3 previous lines of therapy. Median PFS and OS were 5.0 months (95% CI 3.2 - 7.1) and 10.4 months (95% CI 7.2 - 11.4) respectively. K-RAS mutation status, number of lines of previous therapy, and site of primary tumour were not predictive of ORR, PFS or OS on univariate testing. Treatment-related adverse events (AEs) occurred in all patients, with the majority being hematological. Dose reductions occurred in 87.5% of patients. 59% required dose delays, and 56% received granulocyte-colony stimulating factor. Grade 3/4 AEs included neutropenia (34%), anemia (16%), thrombocytopenia (12.5%), febrile neutropenia (9%), diarrhea (6%), and anorexia (3%). Conclusions: Xeloxiri is efficacious and safe in patients with chemo-refractory CRC and is a promising treatment strategy as salvage. Clinical trial information: in progress.