A dose finding study with erlotinib in combination to irinotecan and capecitabine in metastatic colorectal cancer (mCRC) patients
13075 Background: Erlotinib is an oral selective and reversible small molecule inhibitor with specificy for the EGFR/HER1. This study evaluated the maximum tolerated dose and the dose limiting toxicity (DLT) of erlotinib when combined to irinotecan and capecitabine. Secondary objectives included the safety profile and the response rate of the combination. Methods: Twenty-two pts (median age 57 yrs, range: 39–69; M/F:12/10) with mCRC refractory to first-line therapy (oxaliplatin-combinations) were accrued. Five dose level combinations with irinotecan (from 180 to 240 mg/m2, day 1, q21), capecitabine (1500 to 2400 mg/m2/d, days 2–15 q21) and erlotinib (50 to 150 mg/d., continuously until progression) were planned. Cycles were repeated every 3 weeks, maximum of 6–8 cycles. Tumor assessments (RECIST criteria) performed every 3 cycles. Maximum tolerated dose was defined as the highest dose where the toxicity rate does not exceed the 30% target level. Patients were enrolled in cohorts of three, and evaluated for first cycle acute toxicity. Results: Three pts entered the first dose group (no DLT), six the second (1 DLT; G4 neutropenic fever), six the third dose group (2 DLT; G3 diarrhea, G4 neutropenic fever), and one (protocol deviation in the dose escalation scheme) the fourth dose group (1 DLT; G3 diarrhea and vomiting). Cutaneous rash and mucositis G3 (no DLT), were documented in one pt (dose group 2). To confirm these results, six pts were additionally accrued in dose groups 2 and 3 showing no DLT. Among twenty evaluable pts, two had an objective response, 15 showed disease stabilization and completed the 6-cycle treatment, 3 had disease progression. Conclusions: Erlotinib at a dose of 100 mg/d, combined with irinotecan 240 mg/m2 and capecitabine 1500 mg/m2/d, (as correspond to dose group 3) has an acceptable safety profile and appears suitable for further investigation. Editorial Assistance by the Scientific Service of the I.T.M.O. group. No significant financial relationships to disclose.