Author | Christopher G. Willett, MD

Articles

Going Beyond Systemic Fluoropyrimidines With Radiation Therapy for Rectal Cancer: What Should Be the Priority?

August 20, 2012

As we look forward, we suggest that the priority should be to further our understanding of the tumor’s interactions with its microenvironment and with the immune system. We think that such an understanding will be critical for advances in locally advanced rectal cancer therapy.

Intensity-Modulated Radiation Therapy for Anal Cancer

November 13, 2009

Historically, the treatment of squamous cell carcinoma of the anal canal has been an abdominoperineal resection (APR), resulting in loss of the anus and rectum with need for a permanent colostomy.

An Odd But Synergistic Couple: Immunotherapy Combined With Radiotherapy

August 01, 2008

Radiation therapy (RT) and immunotherapy of cancer both date back more than 100 years, and yet, because radiation was often considered immunosuppressive, there had been little enthusiasm for combining them until recently. Immunotherapy has an established role in the treatment of some cancers-superficial bladder cancer treated with bacillus Calmette-Guérin (BCG), renal cell carcinoma and melanoma treated with interferon and interluekin (IL)-2 (Proleukin), and breast cancer and lymphoma treated with monoclonal antibodies such as trastuzumab (Herceptin) and rituximab (Rituxan), which partly function through antibody-dependent cellular cytotoxicity.

Targeted Therapy in Rectal Cancer

August 01, 2007

Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) are often overexpressed in colorectal cancer and are associated with inferior outcomes. Based on successful randomized phase III trials, anti-EGFR and anti-VEGF therapeutics have entered clinical practice. Cetuximab (Erbitux), an EGFR-specific antibody, is currently approved in the United States in combination with irinotecan (Camptosar) for patients with metastatic colorectal cancer refractory to irinotecan or as a single agent for patients unable to tolerate irinotecan-based therapy. In retrospective analyses, patients with EGFR-expressing rectal cancer undergoing neoadjuvant radiation therapy had a significantly inferior disease-free survival and lower rates of achieving pathologic complete response. Based on the positive data in metastatic colorectal cancer and synergy with radiation therapy seen in preclinical models, there is a strong rationale to combine cetuximab with neoadjuvant radiation therapy and chemotherapy in rectal cancer. Bevacizumab (Avastin), a VEGF-specific antibody, was the first antiangiogenic agent to be approved in the United States for use in combination with standard chemotherapy in the first- and second-line of treatment in metastatic colorectal cancer. VEGF-targeted therapy may lead to indirect killing of cancer cells by damaging tumor blood vessels, and may increase the radiosensitivity of tumor-associated endothelial cells. VEGF blockade can also "normalize" tumor vasculature, thereby leading to greater tumor oxygenation and drug penetration. This review will address completed and ongoing trials that have established and continue to clarify the effects of these agents in rectal cancer.