Targeted Therapies + Chemo Show Activity in Recurrent/Metastatic Head And Neck Cancer

Notably, the toxicity was modest for a palliative regimen except for rash, which is of course a marker of response to cetuximab. But neutropenia and rash appeared to be manageable on this weekly regimen. It seems then that the bedside test of rash remains the best predictor of disease control.

Dr. Kim’s study established a maximum total dose for the combination of erlotinib, docetaxel, and cisplatin, Dr. Posner said in his discussant’s remarks. Again, there was a low complete response rate of 8 percent, but the overall response rate was an impressive 66 percent. There was also an impressive median survival, with progression-free survival of six months, and, notably, 48 percent of patients were alive at one year. Except for neutropenia, toxicity was mild for an every-three-week regimen.

Researchers should think strongly about combination therapies with cytotoxic and targeted agents, he said. Cetuximab and erlotinib have single-agent activity. Cetuximab arguably has greater activity in Phase II single-agent trials than erlotinib does. Cetuximab activity is additive with cisplatin. There are no solid data with taxanes for either agent.

Both studies show increased response rates compared with historical controls of roughly 60%, Dr. Posner continued. Paclitaxel and docetaxel as single agents show response rates of 30%, and docetaxel-cisplatin combinations show response rates in the 40% range. Cisplatin as a single agent produces a response rate of 10% to 15%. Cetuximab as a single agent has a 10% to 14% response rate and, in combination with cisplatin, 25%. From a historical point of view, these agents appear to be better than doublets or singlets, he said.

Randomized trials will be necessary to compare combination therapies with targeted agents. I believe a crossover design should be used to estimate the real impact on survival. For palliation, toxicity and progression-free survival are major considerations for patients.

The clinical assessment of rash still remains the best predictor of benefit with cetuximab. It would be very important to identify other prognostic factors to help us to determine who might benefit from the use of cetuximab, Dr. Posner said.

©2008 The Triological Society