A triplet combination with capecitabine/oxaliplatin/irinotecan (XELOXIRI) plus cetuximab as first-line therapy for patients with metastatic colorectal cancer: a dose escalation study

Abstract

Purpose

The addition of cetuximab to triplet chemotherapy can increase treatment efficacy for patients with metastatic colorectal cancer (mCRC). We explored the dose-limiting toxicity and feasibility of a triweekly capecitabine, oxaliplatin, irinotecan, plus cetuximab (XELOXIRI plus cetuximab) regimen in patients with wild-type KRAS mCRC.

Methods

Patients received oxaliplatin (100 mg/m², day 1), capecitabine (1700 mg/m² per day from day 2 to 15), irinotecan (100, 120, and 150 mg/m² for dose levels 1, 2, 3, respectively, on day 1), and cetuximab (400 mg/m², day 1 and, thereafter, 250 mg/m² every week), repeated every 3 weeks. Dose-limiting toxicities (DLTs) were assessed in the first 2 treatment cycles to determine the maximum tolerated dose (MTD) and the recommended dose (RD).

Results

Twelve patients received a median of 7 cycles of therapy (range 2–10). The DLT was grade 4 neutropenia, observed in 1 of 6 patients at dose level 2. The MTD was not reached at dose level 3. Therefore, the RD of irinotecan was defined as 150 mg/m². Most common grade ≥ 3 toxicities were neutropenia (50%), diarrhea (17%), and febrile neutropenia (8%). The response rate was 83% (complete and partial response: 1 and 9 patient(s), respectively), including 4 conversion cases.

Conclusions

The combination of XELOXIRI and cetuximab is feasible and has an acceptable toxicity profile; neutropenia was the DLT. The RD of irinotecan is 150 mg/m². The observed response rate was promising and warrants further investigation.

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