Cancer Therapy Advances: Targeted Agents Show Promise

Researchers in the United States have made significant advancements in cancer therapy using targeted agents, as outlined in three studies published in various medical journals. These studies explore the efficacy and tolerability of combining bevacizumab and erlotinib, the antitumor activity of HER-2 inhibitors, and the antiangiogenic properties of cetuximab. The results suggest that these targeted agents may offer improved treatment options for patients with metastatic renal cell carcinoma, HER-2 dependent tumors, and other types of cancer.

Key Takeaways:

• A combination of bevacizumab and erlotinib was found to be an effective and well-tolerated treatment for patients with advanced renal cell carcinoma, with 25% of assessable patients experiencing objective responses to treatment and 61% having stable disease after 8 weeks.
• The median and 1-year progression-free survival rates for patients treated with this combination were 11 months and 43%, respectively, with median survival not having been reached after a median follow-up of 15 months.
• The efficacy of bevacizumab and erlotinib in combination suggests that targeting separate pathways critical to tumor growth and dissemination may achieve results superior to either drug as a single agent.
• The antitumor activity of HER-2 inhibitors was examined in a recent review, which discussed the potential use of therapeutic antibodies and small molecule kinase inhibitors targeting EGFR and HER-2 in inhibiting the growth of tumors that overexpress HER-2.
• Cetuximab, an antiepidermal growth factor receptor monoclonal antibody, was found to reduce cellular levels of hypoxia-inducible factor-1 alpha (HIF-1 alpha), a transcriptional regulator of VEGF expression, in A431 epidermoid carcinoma cells under both normoxic and hypoxic culture conditions.
• The use of cetuximab in combination with approaches inhibiting the function of VEGF or the VEGF receptor may warrant further testing as a therapeutic strategy.

Statistics:

• 63 patients with metastatic clear-cell renal carcinoma were treated with a combination of bevacizumab and erlotinib in Study 1.
• 15 (25%) of 59 assessable patients experienced objective responses to treatment, and 36 patients (61%) had stable disease after 8 weeks of treatment in Study 1.
• The median progression-free survival rate was 11 months, and the 1-year progression-free survival rate was 43% in Study 1.
• The median survival rate had not been reached after a median follow-up of 15 months in Study 1.

Sources:

• Hainsworth JD, et al. Treatment of metastatic renal cell carcinoma with a combination of bevacizumab and erlotinib. J Clin Oncol, 2005;23(31):7889-7896.
• Rabindran SK, et al. Antitumor activity of HER-2 inhibitors. Cancer Lett, 2005;227(1):9-23.
• Luwor RB, et al. The antiepidermal growth factor receptor monoclonal antibody cetuximab/C225 reduces hypoxia-inducible factor-1 alpha, leading to transcriptional inhibition of vascular endothelial growth factor expression. Oncogene, 2005;24(27):4433-4441.