New Treatment for Head and Neck Cancer Means Longer-Lasting Toxicity

MASCC’s 2005 guidelines for limiting the effect of oral mucositis are the most recent. They include:

• Midline radiation blocks and three-dimensional RT to reduce mucosal injury.
• Use of benzydamine to prevent radiation-induced mucositis with moderate-dose RT.
• Oral cryotherapy for 30 minutes for patients receiving bolus 5-fluorouracil (5-FU) and bolus edatrexate.
• Cryotherapy for patients receiving high-dose melphalan.

Mucositis Treatment

The only agent approved for prevention of oral mucositis is palifermin (Kepivance), a modified recombinant keratinocyte growth factor. It has a number of biologic activities that appear to protect the mucosal epithelium: inhibition of epithelial cell apoptosis and DNA damage; upregulation of detoxifying enzymes; downregulation of proinflammatory cytokines; and enhanced migration, proliferation, and differentiation of epithelial cells.

When given intravenously (40 mcg/kg) for three days prior to chemotherapy and three days following, it reduces the incidence, severity, and duration of oral mucositis and decreases febrile neutropenia and the need for opioid analgesia and tube feeding.

A report by Patrick Stiff, MD, in 2006 in the Journal of Clinical Oncology confirmed that palifermin has clinical benefit when used with stem cell transplant. Two hundred twelve patients received palifermin or placebo before and after total body irradiation (12 Gy), etoposide 60 mg/kg, and cyclophosphamide 100 mg/kg.

Patient self-assessment and physicians’ observations were similar. Those who received palifermin had significant improvements in ability to swallow, drink, and eat, and they needed fewer narcotics.

Another 2006 JCO report by Lee S. Rosen, MD, compared placebo and palifermin for three days before each of two cycles of 5-FU/leucovorin in patients with colorectal cancer. The incidence of grade 2 or higher mucositis was lower in palifermin patients than in the placebo group: 29% vs 61% in the first cycle, and 11% vs 47% in the second cycle. The drug was well tolerated and resulted in a statistically significant and clinically meaningful reduction in mucositis.

The only other effective treatment is low-level laser therapy, which can delay the rate of mucositis by as much as 60%, as well as progression of mild toxicity to a more severe form in patients who have undergone stem cell transplant. It significantly reduces pain.

Cetuximab

Perhaps the best news for head and neck cancer patients in recent years is addition of cetuximab to surgery, chemotherapy, and radiation. The FDA approved it as a radiation sensitizing agent and for treatment of recurrent metastatic disease.

Cetuximab in combination with RT has demonstrated enhanced tumor control without increased significant toxicity. Because of this success, researchers are evaluating its use as part of multimodality treatment in locally advanced disease.