NCCN updates head and neck cancers guide

The recently updated National Comprehensive Cancer Network (NCCN) Head and Neck Cancers Clinical Practice Guidelines address tumors arising in the lip, oral cavity, oropharynx, hypopharynx, glottic and supraglottic larynx, paranasal sinuses, nasopharynx, and salivary glands, as well as occult primary cancer.

For cancers of the oropharynx, hypopharynx, and glottic and supraglottic larynx, cisplatin is now listed as the preferred agent if using the treatment option of concurrent systemic/radiation therapy. "Cisplatin is a radiosensitizer, improving the efficacy of radiation," stated Sarah L. Scarpace, Pharm.D., BCOP, assistant professor of pharmacy practice at Albany College of Pharmacy in New York. "It has been the standard of care for a while, and, for patients who can tolerate it, chemoradiotherapy with cisplatin remains the standard of care."

Key trials

One of the key trials that demonstrated cisplatin's efficacy in patients with unresectable squamous cell head and neck cancers (H&NC) was a phase III randomized trial conducted between 1992 and 1999 by the Head and Neck Intergroup. Eligible patients (n = 295) were randomly assigned to receive single daily fractionated radiation (arm A); identical radiation therapy with concurrent bolus cisplatin (arm B); or a split course of single daily fractionated radiation and three cycles of concurrent infusional 5-FU and bolus cisplatin chemotherapy (arm C). There was a median follow-up at 41 months, with the three-year projected overall survival for patients enrolled in arm A at 23%, compared with 37% for arm B and 27% for arm C. The investigators concluded that the addition of concurrent high-dose, single-agent cisplatin to conventional single-daily fractionated radiation significantly improves survival, although it also increases toxicity.

In the guidelines, definitive radiation therapy plus cetuximab was added for patients with advanced H&NC not able to tolerate cytotoxic chemotherapy. The efficacy of cetuximab in H&NC was evaluated in a phase III trial consisting of 424 patients with stage III or IV head and neck cancer. Patients were randomly assigned to receive either radiation therapy alone (n = 213) or radiation plus weekly cetuximab (n = 211). The results showed that patients treated with cetuximab had a median survival of 49 months, compared with 29.3 months for patients who received radiation therapy alone. Fifty-five percent of the cetuximab-treated patients survived for three years, compared with 45% of those in the radiation-only group.

Better tolerability

"Cetuximab causes less nausea and vomiting and does not increase radiation-related side effects," Scarpace said. "Though the cetuximab data are impressive, it would be ideal to have a randomized trial comparing cetuximab and radiation with cisplatin and radiation. The survival differences in the radiation control arms of the Intergroup trial and the cetuximab trial are very different, suggesting that the populations may have been different and thus not directly comparable." In the cetuximab trial, patients in both groups suffered from severe mucositis in roughly equal amounts: 52% of the radiation-only group and 56% of the cetuximab combination group. The investigators noted that the increase in survival with cetuximab was attained with no worsening of radiation-induced adverse effects.

The NCCN Clinical Practice Guidelines are available free of charge at http://www.nccn.org/.

THE AUTHOR is a writer based in New Jersey.