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Why is continued VEGF inhibition important?

Regrowth of tumor vasculature may occur when VEGF inhibition is stopped

While continued VEGF inhibition maintains important anti-angiogenic effects that keep tumor cells from growing and spreading, cessation of VEGF suppression may diminish those effects. In preclinical models, withdrawal of an anti-VEGF agent has been shown to result in regrowth of tumor vasculature (Fig. 1).^1-5

This research suggests that vascular regrowth may be a normal physiologic response to the removal of VEGF inhibition. In particular, both the rate and the amount of vascular regrowth observed following withdrawal of VEGF inhibition has been consistent with normal tumor development.^1,5

Fig. 1. Tumor vessel regrowth following withdrawal of an anti-VEGF agent²

Adapted from Vosseler et al 2005. Reproduced with permission from the American Association for Cancer Research.

The rationale for continuing VEGF inhibition as observed in preclinical models

Emerging research now suggests that continuing direct VEGF inhibition alone may help preserve antitumor effects achieved following initial combination with chemotherapy. In one preclinical model, continuation of VEGF inhibition following initial combination with chemotherapy inhibited tumor recurrence and significantly prolonged survival in mice (Fig. 2).⁶

Fig. 2. PRECLINICAL EVIDENCE: prolonged survival with continued VEGF inhibition (mouse model)⁶

In vivo experiment using the ovarian cancer cell line, Caov-3.

These proposed effects influence clinical trial design

Specifically, many clinical trials with anti-VEGF agents have been designed to maintain VEGF inhibition, even in instances in which administration of accompanying antitumor compounds may be modified.^7-10

Further exploration

• Detailed look: Role of VEGF throughout tumor development
• Related topic: Why do tumors progress?

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References:

1.

Mancuso MR, Davis R, Norberg SM, et al. J Clin Invest. 2006;116:2610-2621.

2.

Vosseler S, Mirancea N, Bohlen P, et al. Cancer Res. 2005;65:1294-1305.

3.

Baluk P, Hashizume H, McDonald DM. Curr Opin Genet Dev. 2005;15:102-111.

4.

Inai T, Mancuso M, Hashizume H, et al. Am J Pathol. 2004;165:35-52.

5.

Aita M, Fasola G, Defferrari C, et al. Crit Rev Oncol Hematol. 2008;68:183-196.

6.

Mabuchi S, Terai Y, Morishige K, et al. Clin Cancer Res. 2008;14:7781-7789.

7.

Hurwitz H, Fehrenbacher L, Novotny W, et al. N Engl J Med. 2004;350:2335-2342.

8.

Sandler A, Gray R, Perry MC, et al. N Engl J Med. 2006;355:2542-2550.

9.

Motzer RJ, Michaelson MD, Redman BG, et al. J Clin Oncol. 2006;24:16-24.

10.

Ratain MJ, Eisen T, Stadler WM, et al. J Clin Oncol. 2006;24:2505-2512.