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Biotech / Medical : Indications -- Cancer -- Ignore unavailable to you. Want to Upgrade?

To: Icebrg who wrote (381)	5/25/2003 5:55:52 AM
From: Icebrg	Read Replies (2) \| Respond to of 1840

Targeting the VEGF Receptor With Bevacizumab [Perhaps, I should have posted this first followed by the abstract. I think it is interesting to see the "speculation" that the cause for the failure in the Avastin breast cancer trial might have been due to the patient selection. Erik] In a randomized trial of 110 patients with metastatic renal cell carcinoma,[19] treatment with the anti-VEGF antibody bevacizumab seemed to significantly prolong time to tumor progression. However, in patients with relapsed metastatic breast cancer treated in a phase 3 study with a combination of capecitabine and bevacizumab,[20] progression-free survival and overall survival at 12-month follow-up did not differ significantly from those of patients receiving capecitabine alone as third-line treatment. The reasons for these disappointing results are still being investigated, but in hindsight, it seems that only a few tumors were expressing active VEGF. As already seen in patients who overexpress HER2, careful selection of potentially sensitive patients is becoming mandatory when evaluating novel therapies aimed at biologically active targets. Identification of surrogate markers might also help to better identify patients that could benefit from these treatments. To evaluate other combinations, trials are in progress with bevacizumab plus other chemotherapeutic agents, such as paclitaxel.[19] The most recent results from a phase 2 trial in patients with metastatic colorectal cancer showed a dose-dependent effect in clinical response.[21] Patients receiving the lower dose of antibody (5 mg/kg every 2 weeks) in combination with 5-fluorouracil/leucovorin (5FU/LV) had a higher response rate, longer time to progression, and longer median survival than patients receiving the higher dose of antibody (10 mg/kg every 2 weeks) in combination with 5FU/LV or FU/LV alone. Thrombosis was the most significant toxicity (causing 1 death), followed by hypertension, proteinuria, and epistaxis. Thus, dose adjustment might also represent a critical factor in optimizing antiangiogenesis therapies. [This was a snippet taken from "Anti-angiogenesis: The Challenges Ahead" which is available at Medscape. medscape.com ]