4097 Background: Targeted therapy against VEGF and EGFR both demonstrated clinical activity in combination with chemo in MCRC. In 1st line, B with Folfox or Xelox increase progression-free survival (Cassidy ESMO 2006). In 2nd L, B with Folfox increases overall survival (Giantonio 2005). In this preliminary study, a double inhibition is tested combining mFolfox+B or mXelox+B with or without E, an oral EGFR tyrosine kinase inhibitor. Methods: 38 pts with untreated MCRC were randomly assigned to: mFolfox+B (1A), mFolfox+B+E (1B), mXelox+B (2A) or mXelox+B+E (2B). mFolfox-B=LV 400 mg/m2, Oxaliplatin (ox) 100 mg/m2, B 5 mg/kg day 1, 5FUc 2.4- 3g/m2 46h q2w, mXelox-B=Ox 100 mg/m2 d1 q2w, capecitabine 3–3.5 g/m2 d1 to 7 q2w, B 5mg/kg q2w. Erlotinib=100 mg/day. 6 cy planned. The primary end-points were toxicity and RR. Results : 9pts/41cy in 1A, 10/60 (1B), 9/39 (2A), 10/44 (2B). Median age 62yrs (43–78). 24/38 pts had poor prognosis factors (>1 met. site and/or PS2, LDH>3N, elevated alk Ph): 5, 6, 7, 6 in each arm respectively. 17 pts had a gr3- 4 toxicity: 4/9 arm 1A, 4/10 arm 1B, 2/9 arm 2A, 7/10 arm 2B. Diarrhea (dia) was the main gr3–4 tox: 2/10pts in 1B, 1/9 in 2A & 6/10 in 2B. 3 pts had gr4 dia in arm 2B. Other gr3 tox were nausea-vomiting 4pts (2/0/0/2), cutaneous rash 2 pts (0/1/0/1), hypertension 1 pt (1B), mucositis 1pt (1A), neutropenia 1 pt (1A), thrombocytopenia 1 pt (1A). 1pt had a gr4 venous thrombosis (2A) and 1pt had pulmonary embolism. 1pt died with perforation in arm 1A, and 1pt died with gr4 dia in arm 2B. Amongst the 17pts with gr3–4 toxicity, 11 pts had poor prognosis criteria and 6 had good prognosis. PR, SD, PD and NE are respectively: arm 1A: 5/2/0/2, 1B: 4/6/0/0, 2A:5/3/1/0, 2B:4/3/0/3. Conclusion: The results of this feasibility phase indicate that adding E with mXelox and bevacizumab increases toxicity (70% gr3–4) and is not feasible. Based on these results, the DREAM study was redesigned to evaluate erlotinib in maintenance with B after 6 cycles of mXelox-B or mFolfox-B. No significant financial relationships to disclose.
Small Renal Masses: Incidental Diagnosis, Clinical Symptoms, and Prognostic Factors
