Despite progress in recent years in the treatment of metastatic colorectal cancer (mCCR), mortality remains high. Molecular Targeted Therapy (MTT), against VEGF (Vascular Epidermal Growth Factor) and EGFR (Epidermal Growth Factor Receptor) constitutes a change in digestive cancerology. Patients and methods: 47 Algerian patients average 57 old years between (22-71) histologically confirmed stage IV colorectal adenocarcinoma, (TNM/UICC) allowed in the Medical Oncology Service of P&M Curie center, Algiers were treated by Folfiri/Bevacizumab protocol. A change of MTT (Folfiri/Cetuximab) is advocated in case of disease progression and implies prior detection of KRAS status. Extraction of DNA tumor is realised from paraffin embedded samples. Amplification, using specific primers in search mutations of this gene followed by sequencing (ABI-PRISM 3100). Determination of VEGF status by ImmunoHistoChemistry (IHQ and amplification of five monomorphic markers followed by sequencing is in search for the RER (Replication of ERror) phenotype in paraffin block samples. Results: from April 2005 to September 2007, 47 mCCR patients with metastasis in liver (n = 34), lungs (n = 7), bones (n = 2) and abdominal lymph nodes (n = 4) submitted to Folfox/Bevacizumab or Folfiri / Bevacizumab protocol are evaluated. There were 3 complete responses (CR), 6.38%, 28 partial responses (PR), 59.57%, 5 stabilizations (SD), 10.63% and 11 progressions (PD), 23.40%. The objective response rate (CR+PR), being 65.95%. The median progression free survival is 12.5 months and overall survival is 18 months. Severe toxicity (Grade 3 and 4, OMS) estimated about 452 cycles with neutropenia (8.4%), thrombopenia (1.8%), vomiting (8.2%), diarrhea (2.9%), mucositis (4.9%) and allergy (0.7%). IHC shows an expression of VEGF in 86.95% patients. KRAS status is researched for patients with disease progression, (n = 11) and one mutation in the KRAS gene is found in 36.4% (n = 4). Consequently, 73.6% patients (n = 8) would potentially respond to cetuximab therapy. Toxicity of this treatment represented by a typical acneiform skin rash was found in one case only. One single treatment was discontinued. The median progression free survival is 14 months. RER status was determined by molecular biology and was found stable in all our patients (100%). Conclusion and discussion: Monoclonal antibodies directed against VEGF and EGFR have shown their efficacy and allow the survival of patients with mCCR in spite of their unfavorable short prognosis. The involvement of KRAS gene mutation as predictor of response to antibody anti-EGFR (Cetuximab) is proved. MTT does not always have a tumor response in all patients and it becomes necessary currently to look for other predictors of response to treatment. Copyright © 2010 Celsius.
