A phase II study of cetuximab/irinotecan in patients with heavily pretreated metastatic colorectal cancer: Predictive value of early specific toxicities

Background: This study was designed to evaluate the predictive value of early specific toxicities on efficacy of weekly irinotecan/cetuximab administered as salvage therapy in patients with metastatic colorectal cancer (CRC) refractory to oxaliplatin and irinotecan. Patients and Methods: Seventy patients received a regimen composed of weekly irinotecan 125 mg/m² as a 1-hour intravenous infusion and cetuximab 400 mg/m² infused over 2 hours as the initial dose and 250 mg/m² infused over 1 hour for subsequent administrations. A single treatment cycle was composed of 4 weekly irinotecan infusions followed by 2 weeks of rest. The predictive value of adverse events (AEs) attributable to cetuximab (rash) and major toxicities attributable to irinotecan (gastrointestinal [G1] and hematologic) were observed after the first cycle of treatment and, therefore, correlated to activity and efficacy of cetuximab and weekly irinotecan. Results: Sixty-six of 70 patients received ≥ 1 cycle of chemotherapy and were therefore evaluable for response. Overall, toxicity observed was generally mild and manageable. According to an intent-to-treat analysis, a partial response was exhibited in 15.7% of patients, with a median progression-free survival (PFS) and median overall survival time of 4 months and 9 months, respectively. As expected, PFS (P = .01) and median survival (P = .04) correlated strongly with the presence and severity of the rash. Surprisingly, the presence of at least moderate hematologic and G1 toxicity was associated with improved PFS (P = .03). Conclusion: Our data suggest that irinotecan-induced AEs might predict a better outcome in advanced CRC. This finding would identify a different subset of patients - those likely to benefit from a renewed sensitivity to irinotecan induced by cetuximab.