Sequential and alternating chemotherapy and radiation equally effective in larynx cancer therapy

Larynx cancer patients treated with alternating cycles of chemotherapy and radiation have similar outcomes to patients treated with chemotherapy followed by radiation, according to data from a randomized controlled trial in the January 27 online issue of the Journal of the National Cancer Institute.

Previous trials in patients with locally advanced larynx cancer showed that chemotherapy followed by radiation was as effective as total removal of the larynx, known as laryngectomy, in terms of overall and disease-free survival and that this sequential therapy provided better quality of life. Subsequent trials indicated that concurrent administration of chemotherapy and radiation resulted in a statistically significant improvement in larynx preservation but was associated with more serious acute toxicity and possibly long term side effects.

To try to improve patient survival without increasing side effects, Jean Lefebvre, M.D., of the Centre Oscar Lambret in Lille, France, and colleagues in the European Organization for Research and Treatment of Cancer enrolled 450 patients with larynx or hypopharynx cancer in a randomized controlled trial. Patients received either chemotherapy followed by radiation or alternating cycles of radiation and chemotherapy.

With a median follow-up of 6.5 years, there was no significant difference in clinical outcomes between the two treatment groups. Larynx preservation, overall survival, and progression-free survival were similar for patients treated with sequential and alternating chemotherapy and radiation.

"The aim of our trial was to identify a regimen that would mimic concomitant chemotherapy and radiotherapy without its increased toxic effects," the authors write. "Although we achieved the latter goal…efficacy was not improved." Given the results of this and several other recently-completed trials, the authors conclude that an optimal approach for larynx-preserving therapy has not been identified.

In an accompanying editorial, Arlene Forastiere, M.D., and Andy Trotti, M.D., of the Sidney Kimmel Cancer Center at Johns Hopkins University in Baltimore and the H. Lee Moffitt Cancer Center at the University of South Florida in Tampa, respectively, concur with that conclusion. The editorialists put the newly-reported data into context, reviewing other trials in the field. They note, however, that because the field currently lacks shared definitions and endpoints, synthesis of data from all the trials is difficult.

"In summary, the [current] trial showed no advantage for alternating chemotherapy and radiotherapy over traditional cisplatin plus 5-fluorouracil induction chemotherapy in hypopharynx cancer," the editorialists write. "More effective and less toxic approaches are needed. This trial also illustrates the need for common definitions and metrics to facilitate interpretation and to compare results across trials."