High-Risk Head and Neck Cancers Largely Resist Chemotherapy Attack

Adding chemotherapy to radiation therapy and surgery failed to significantly improve control of high-risk, resected head and neck cancers, according to a new study presented October 7, 2002, at the American Society for Therapeutic Radiology and Oncology's Annual Meeting in New Orleans.

Researchers set out to discover whether the most aggressive, high-risk squamous cell carcinoma patients who had their cancers surgically removed were less likely to have local or regional recurrence of the disease if the chemotherapy drug cisplatin was given concurrently with post-operative radiation therapy.

A total of 459 patients were enrolled in the study. Patients were eligible only if they had squamous cell carcinoma of the head and neck region that was classified as high risk, meaning that their tumors invaded two or more lymph nodes, extended beyond a lymph node capsule and/or microscopically involved mucosal margins of resection. After having all visible and/or palpable areas of cancer surgically removed, 231 patients were randomly assigned to have radiation therapy alone, and 228 were randomly assigned to have identical radiation therapy plus the chemotherapy drug cisplatin.

With a current median follow-up of 37 months, the two-year local-regional control rate was 74 percent for the group that received radiation therapy alone, and 79 percent for the group that received radiation therapy and chemotherapy. One hundred thirty one patients were alive at three years follow-up, 124 of the 131 (95 percent) did not have a local-regional recurrence at that time. Local-regional recurrence as the site of first treatment failure occurred in 26 percent in the group receiving radiation therapy and 19 percent of the group receiving concurrent combined therapy. Distant metastasis as the first site of failure occurred in 23 percent of the radiation therapy group, and 19 percent of the concurrent group. None of these differences are statistically significant. On the other hand, 58 percent of patients who did not receive chemotherapy had some form of recurrent disease versus 45 percent of patients who did receive chemotherapy, a statistically significant difference.

"We primarily sought to learn whether the addition of cisplatin chemotherapy to post-operative radiation therapy would improve the likelihood of local-regional control of head and neck cancer for this selected subgroup of particularly aggressive resected tumors," said Jay S. Cooper, M.D., of NYU Medical Center and lead author of the study. "We are disappointed to learn that despite added toxicity from the addition of chemotherapy, local-regional control, distant control, overall survival and disease-free survival were not significantly improved. On the bright side, we did demonstrate that we can reliably identify this aggressive group of tumors from features seen on pathology examination, which should improve selection of patients for future trials and treatments. We also have demonstrated that with modern techniques and meticulous attention to the details of our gold-standard treatment, surgery followed by radiation therapy, even for these high-risk tumors, we have reduced the rate of local-regional recurrence to the point that only one of four patients have treatment fail them in this fashion. Lastly, the significant difference observed for treatment failure of any type suggests that we are headed in the right direction, but need to identify more effective agents."