• 6/5/2003
  • Chicago
  • Charlene Laino

In a finding that some physicians say could transform the management of people with locally advanced head and neck cancer, researchers have found that adding paclitaxel to the standard chemotherapy regimen completely wipes out tumors in about one third of patients, extending lives. Patients given the paclitaxel combination are also more likely to retain the ability to speak and swallow, resulting in improved quality of life, said Ricardo Hitt, MD, PhD, an oncologist at the Hospital 12 de Octubre in Madrid, Spain, and the chief investigator of the new study.

Based on results of a phase II trial pitting paclitaxel plus the standard regimen of cisplatin and 5-fluorouracil (5-FU) against the standard regimen alone, the researchers hypothesized that the triplet would shrink more tumors, extending survival. Which is just what happened, Dr. Hitt reported here at the 39th annual meeting of the American Society of Clinical Oncology. In the prospective, randomized phase III study of 384 patients with locally advanced head and neck cancers, mostly tumors of the oropharynx, larynx, and oral cavity, patients were randomly assigned to receive either 100 mg/m2 of cisplatin on day 1 plus a continual infusion of 1 g/m2 of 5-FU for five days every three weeks, or the same drugs plus 175 mg/m2 of paclitaxel on day 1 of each cycle. About 35% of the patients, whose median age was 56 years, had resectable disease. Three quarters had a performance status of 1, and 84.1% had stage IV disease.

Tumors disappeared in 32% of those who received the triple therapy. In contrast, conventional chemotherapy was associated with a complete response rate in 13% (P < .007), Dr. Hitt said.
The difference in partial response rates between the two groups was not quite as striking: Tumors shrank by 50% or more in 56% of patients given the paclitaxel combination compared with 48% of those receiving conventional chemotherapy, the study showed.
But as follow-up continues, “many of the patients who received the paclitaxel combination have already survived more than 38 months, the median survival time for the standard chemotherapy regimen,” Dr. Hitt said. The median time to progression for patients who received the paclitaxel combination was 23 months compared with 18 months for those treated with the standard drugs. In addition, the larynx, pharynx, and tongue were preserved in 88% of patients who received the paclitaxel combination compared with 75% of those who were treated with cisplatin and 5-FU alone.

Adverse effects were similar among patients in both groups, except for grade 3 to 4 mucositis, which was significantly more common in patients receiving standard therapy: 23.3% vs. 3.1% in the paclitaxel arm, the study showed. Given its superior efficacy and toxicity profile, “this combination may soon become the standard treatment option for some patients with head and neck cancer,” Dr. Hitt said. ASCO spokespersons who were not involved with the study generally agreed.
“This is a very important study that will very likely change the way head and neck patients are managed,” said Robert Mayer, MD, director of the Center for Gastrointestinal Oncology at Dana-Farber Cancer Institute in Boston, Massachusetts, and moderator of a discussion on the findings. Frank Haluska, MD, chair of ASCO’s Cancer Communications Committee, said that while practice guidelines are rarely changed based on one study, “there is very little downside to physicians adopting this regimen immediately.”

Head and neck cancer is a relatively chemoresponsive tumor, but adding paclitaxel “clearly results in better complete response rates,” said Dr. Haluska, an oncologist at Massachusetts General Hospital in Boston. “This is really important for the patient, representing not only a step toward a cure but also allowing for treatment to preserve the larynx and the voice.” Plus, toxicity is very tolerable, he said.
Bristol-Myers Squibb helped fund the study.

ASCO 39th Annual Meeting: Abstract 1997. Presented June 1, 2003