Cetuximab rechallenge in metastatic colorectal cancer patients: how to come away from acquired resistance?

BACKGROUND: Scientific data provide the evidence that secondary K-RAS mutations do not occur during anti-epidermal growth factor receptor therapy in colorectal cancer patients. This multicenter phase II prospective study aims to investigate the activity of a retreatment with a cetuximab-based therapy. PATIENTS AND METHODS: We enrolled 39 irinotecan-refractory patients who had a clinical benefit after a line of cetuximab- plus irinotecan-based therapy and then a progression of disease for which underwent a new line chemotherapy and finally, after a clear new progression of disease, were retreated with the same cetuximab- plus irinotecan-based therapy. RESULTS: Median number of therapeutic lines before accrual was 4. Median interval time between last cycle of first cetuximab-based therapy and first cycle of the retreatment was 6 months. Overall response rate was 53.8% with 19 partial responses (48.7%) and 2 complete responses (5.1%). Disease stabilization was obtained in 35.9% of patients and progression in four patients (10.2%). Median progression-free survival was 6.6 months. The correlation between skin toxicity during first cetuximab therapy and during cetuximab rechallenge was significant (P = 0.01). CONCLUSION: Rechallenge with the same cetuximab-based therapy may achieve a new important clinical benefit further delaying the progression of disease and improving the therapeutic options.

New perspectives: role of Sunitinib in breast cancer.

Sunitinib malate (SU11248) is a multitarget oral tyrosine kinase receptor (RTKs) inhibitor which was approved by FDA in renal cells carcinoma (RCC) and imatinib-resistant or imatinib-intollerant gastro-intestinal stromal tumour (GIST). Sunitinib is able to inhibit RTKs such as receptors for platelet-derived growth factor (PDGF-Rα and ß) and for vascular endothelial growth factor (VEGFRs). It is able to inhibit KIT receptor, colony stimulating factor type 1 receptor (CSF-1R), glial cell line neutrophic factor receptor (RET), fms-like tyrosine kinase receptor-3 (FLT-3 or CD135), signal transducer and activator of transcription 3 (STAT3) and AKT (protein kinase B) in tumour cells. Many Sunitinib targets play important roles in growth and survival of human breast cancer (BC). The "rationale" of Sunitinib in BC (with or without others antiagiogenetic therapy) is its ability to block simultaneously intracellular portion of RTKs inhibiting many downstream signals. We overviewed the most relevant studies concerning Sunitinib in metastatic BC.

New perspectives: role of sunitinib in breast cancer.

Sunitinib malate (SU11248) is a multitarget oral tyrosine kinase receptor (RTKs) inhibitor which was approved by FDA in renal cells carcinoma (RCC) and imatinib-resistant or imatinib-intollerant gastrointestinal stromal tumour (GIST). Sunitinib is able to inhibit RTKs such as receptors for platelet-derived growth factor (PDGF-R alpha and beta) and for vascular endothelial growth factor (VEGFRs). It is able to inhibit KIT receptor, colony stimulating factor type 1 receptor (CSF- 1R), glial cell line neutrophic factor receptor (RET), fms-like tyrosine kinase receptor-3 (FLT-3 or CD135), signal transducer and activator of transcription 3 (STAT3) and AKT (protein kinase B) in tumour cells. Many sunitinib targets play important roles in growth and survival of human breast cancer (BC). The "rationale" of sunitinib in BC (with or without others antiagiogenetic therapy) is its ability to block simultaneously intracellular portion of RTKs inhibiting many downstream signals. We overviewed the most relevant studies concerning sunitinib in metastatic BC.