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Treatment of Metastatic Colorectal Cancer With Monoclonal Antibody to Vascular Endothelial Growth Factor: Does the Metastatic Site Make the Difference?

¹ Medical Oncology Unit, Hospital of Urbino, Urbino
² Medical Oncology, University of Ancona, Ancona, Italy

We read with great interest the article by Kabbinavar et al,¹ who reported the results of fluorouracil-based chemotherapy in combination with recombinant humanized antibody to vascular endothelial growth factor (VEGF) in metastatic colorectal cancer. They found encouraging results using this innovative approach, but imbalances in baseline characteristics across the treatment arms raise some concerns. In particular, we would like to emphasize the difference in the proportion of patients with liver-lung metastases and the lack of information on patients with abdominal metastases. In a previous investigation we found significant lower VEGF expression levels in liver metastases than in abdominal metastases.² Also, angiogenesis scores were significantly lower for metastatic lesions than for the primary tumor, and metastatic colorectal carcinomas showed significant lower VEGF expression in liver recurrences compared with the primary tumor.^3–6 Dirix et al⁷ showed variable VEGF serum levels according to the metastatic pattern of colorectal carcinomas.

In the study by Kabbinavar et al,¹ patients treated with fluorouracil alone showed a lower proportion of liver-lung metastases than patients treated with fluorouracil plus bevacizumab. Also, the authors did not report the frequency and the distribution in the treatment arms of abdominal metastases. Patients treated with low-dose bavacizumab had better outcomes than patients treated with high-dose of bevacizumab, and it would be interesting to know the distribution of abdominal metastases in these two groups.

Future studies with monoclonal antibodies to VEGF should consider the heterogeneity in the VEGF expression in colorectal cancer metastatic sites, and a stratification of enrolled patients according to the metastatic pattern.

AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

The authors indicated no potential conflicts of interest.

REFERENCES

1. Kabbinavar F, Hurwitz HI, Fehrenbacher L, et al: Phase II, randomized trial comparing Bevacizumab plus fluorouracil (FU)/leucovorin (LV) with FU/LV alone in patients with metastatic colorectal cancer. J Clin Oncol 21:60–65, 2003[Abstract/Free Full Text]

2. Cascinu S, Graziano F, Catalano V, et al: Differences of vascular endothelial growth factor (VEGF) expression between liver and abdominal metastases from colon cancer: Implications for the treatment with VEGF inhibitors. Clin Exp Metastasis 18:651–655, 2001

3. Mooteri S, Rubin D, Leugrans S, et al: Tumor angiogenesis in primary and metastatic colorectal cancers. Dis Colon Rectum 39:1073–1780, 1996[CrossRef][Medline]

4. Berney CR, Yang JL, Fisher RJ, et al: Vascular endothelial growth factor expression is reduced in liver metastasis from colorectal cancer and correlates with urokinase-type plasminogen activator. Anticancer Res 18:973–978, 1998[Medline]

5. Berger DP, Herbstritt L, Dengler WA, et al: Vascular endothelial growth factor (VEGF) mRNA expression in human tumor models of different histologies. Ann Oncol 8:817–825, 1995

6. Brown LF, Berse B, Jackman RW, et al: Expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in adenocarcinomas of the gastrointestinal tract. Cancer Res 53:4727–4735, 1993[Abstract/Free Full Text]

7. Dirix LY, Vermeulen PB, Hubens G, et al: Serum basic fibroblast growth factor and vascular endothelial growth factor and tumor growth kinetics in advanced colorectal cancer. Ann Oncol 7:843–848, 1996[Abstract/Free Full Text]

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