Dose-finding study of fixed dose rate (FDR) infusion of gemcitabine in combination with bevacizumab and escalating doses of irinotecan in patients with advanced gastrointestinal (GI) tumors

Abstract

13068 Background: Gemcitabine (GMB), Bevacizumab and Irinotecan (CPT-11) are active agents in GI tumors with preclinical evidence of synergism. The purpose of this study was to assess the maximum tolerated dose (MTD) of FDR GMB, Bevacizumab and CPT-11 in patients (pts) with advanced GI malignancies. Preliminary evidence of antitumor activity was also evaluated. Methods: A biweekly schedule of FDR GMB at a dose of 1000 mg/m2, Bevacizumab 5 mg/kg and CPT-11 (100–160 mg/m2 with a 10 mg/m2 increase in each cohort level) was analysed. The dose of CPT-11 was escalated in cohorts of three pts until the MTD was defined. Results: Thirty eligible pts with GI tumors were included (oesophagus: 2; gastroesophagic junction: 1; gastric: 2; pancreas: 2; colon: 17; rectum: 6) The median age was 60 years. ECOG status was 0–1 in 70% of pts. Male/female ratio was 21/9. Twenty-nine pts had received prior chemotherapy. The median number of cycles administered was six. Two of three pts at a CPT-11 dose of 160mg/m2 had grade 3 asthenia that required hospitalization. Recommended dose was thus established at CPT-11 dose of 150 mg/m2. Nine additional pts were included in this cohort and no further toxicity was observed. Antitumor activity was seen in 13 pts, with 3 complete responses and 10 partial responses. Conclusions: The recommended dose for phase II studies is CPT-11 150 mg/m2, GMB 1000 mg/m2 in FDR infusion and Bevacizumab 5 mg/kg on a biweekly schedule. Overall, this is a feasible regimen with a promising activity. No significant financial relationships to disclose.