Gefitinib in Combination with Capecitabine as Second-Line Therapy in Patients with Advanced Colorectal Cancer (aCRC): A Phase I/II Study of the Arbeitsgemeinschaft Internistische Onkologie (AIO)

Abstract

Background: This phase I/II study was conducted to assess the maximal tolerated dose (MTD) and the dose-limiting toxicities (DLTs) of gefitinib in combination with capecitabine in patients with advanced colorectal cancer (aCRC). Patients and Methods: After failure of a 1st-line therapy, patients with aCRC received escalating doses of gefitinib once daily in combination with capecitabine twice daily: dose level (DL) 1: gefitinib 250 mg and capecitabine 1,000 mg/m², DL 2: gefitinib 250 mg and capecitabine 1,250 mg/m², DL 3: gefitinib 500 mg and capecitabine 850 mg/m². DLTs were determined after 6 weeks of treatment. Results: A total of 16 patients were enrolled. On DL1 (n = 6), 1 patient developed a DLT (hand-foot syndrome, HFS n = 1). On DL2 (n = 7), DLTs were observed in 3 patients (exanthema n = 2, HFS n = 1), and on DL3 (n = 3), DLT occurred in 1 patient (HFS n = 1) resulting in recruitment stop at DL3. No patient showed an objective tumor response. Disease stabilization was observed in 6 patients. Conclusion: The combination of gefitinib and capecitabine resulted in significant skin toxicities such as exanthema and HFS. As 2nd-line treatment of patients with aCRC, this combination showed no substantial efficacy.