Colorectal Cancer Cetuximab is currently under phase II clinical trial in Europe for metastatic colorectal cancer (mCRC). To evaluate the effectiveness of cetuximab monotherapy on mCRC, 346 patients with mCRC refractory to both irinotecan and oxaliplatin were treated with cetuximab. Results showed that cetuximab had OR rate of 12% and mean survival of 6.6 months. The combination therapy including cetuximab and bevacizumab were evaluated in a radomly study trial. Results showed that Cetuximab together with bevacizumab demonstrated no toxicity effect. The combination results in 38% OR rate. The combination of cetuximab and bevacizumab had 23% OR rate. The survival rate increased to 8.5 months. There is another EGFR antibody under phase II multicenter clinical trial for mCRC, panitumumab. The single treatment by panitumumab can reduce the risk of tumor progression by 46%. Lung Cancer. Erlotinib is now marketed for treatment of advanced NSCLC. The Phase III clinical trial involved 731 patients with metastatic NSCLC. Results showed the monotherapy by erlotinib could increase the 1 year survival in 10% population, which had been through the first- or second-line chemotherapy. Gefitinib was under phase II clinical trial for advance NSCLC with dose of 250-500 mg per day. A phase III clinical trial showed no significant survival benefit from gefitinib monotherapy compared with placebo. These results lead to the denial of marketing. For 1692 patients, gefitinib significantly reduce the size of cancer tissue, but these exciting results didn’t translate into the improvement of life survival. The combination therapy was also under clinical trial. A phase I/II study of erlotinib 150mg/day combined with bevacizumab 15mg/kg showed 20% PR rate, 12.6 month median survival. progression becuase cancer cells needs oxygen and nutrition to keep growth. VEGF is a receptor tyrosine kinase that mediates the growth of blood vessel especially in cancer tissue. Blocking VEGF is to eliminate the supply of tumor growth and thus inhibit the progression of tumor. Although effective, the inhibitor of VEGF still has its limitations. For example, some tumor resist the effect of VEGF inhibitor treatment. Inhibitors of VEGF, together with other receptor tyrosine kinase, are the first choice for treating advance renal cell carcinoma (RCC)[1]. Tivozanib is a novel orally available small molecule and is found to be an effective inhibitor of VEGF. It potentially inhibits all three types of VEGF, therefore maximize its on-target effect and limit its off-target toxicity. Phase II clinical trial showed that tivozanib is well tolerated and significantly prolonged the life of patients with advance renal cell carcinoma. The phase III clinical trial, aim to examine widely the effectiveness and safety of the drug, is now in progress. Soon after, the drug will marketed in both USA and Europe. BIBF 1120 (Vargatef) is a newly developed compound which could inhibit all of three receptors classes and thus completely block the stimulation mechanism of angiogenesis. Ideally, BIBF1120 could prevent both tumor growth and metastasis. Indeed, BIBF1120 reduced the tumor progression in lab animals for many types of solid tumors. Based on these results, BIBF1120 is now under phase I clinical trial for non-small cell lung cancer in healthy human. Ellis et al (1) selected thirty one patients in this study. Among them, 21 patients complete this study. The most common adverse effect are nausea, vomiting, abdominal pain and diarrhea. Other side effect includes fatigue, nausea, anorexia, rash, diarrhea and vomiting. In conclusion, BIBF 1120 and pemetrexed together is a good choice for further clinical trial. [1] Nat Rev Drug Discov. 2011 Apr;10(4):248 Related Posts: 1. The overview of targeting EGFR for solid tumor 1 2. Epidermal Growth Factor, a target for killing cancer
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