Source: www.modernmedicine.com
Author: Gabriel Miller

The latest data from a trial that opened in 1992 confirm that for locally advanced laryngeal cancer, sequential and concomitant chemoradiotherapy each produce similar survival rates, but the concomitant approach more often allows the larynx to be preserved.

When the results of RTOG 91-11 were first published in 2003. “they changed the standard of care treatment for preserving the larynx from the sequential use of chemotherapy then radiotherapy to giving both together,” said lead investigator Dr. Arlene Forastiere of Johns Hopkins University in an email to Reuters Health.

“The results have held up over the last decade,” she said, “…and this exact treatment remains the standard of care today because on average, 15% will ultimately require laryngectomy with the concomitant approach, compared to double that, or 30%, with either giving chemotherapy and radiation in sequence or giving radiotherapy alone.”

“There’s no question that this study has changed the way we approach and treat this disease, so it is truly a landmark study,” said Dr. Chris Holsinger, a head and neck cancer surgeon at MD Anderson Cancer Center in Houston, Texas who wasn’t involved in the research.

Between 1992 and 2000, 547 patients were randomly assigned to three treatment groups: induction chemotherapy followed by radiation; concomitant chemoradiotherapy; and radiotherapy alone.

The induction group received up to three cycles of cisplatin 100 mg/m2 on day one and fluorouracil 1,000 mg/m2 per day for five days, every three weeks. Responders then received up to 70 Gy of radiotherapy in 35 treatments of 2 Gy fractions.

Those in the concomitant chemoradiotherapy group received cisplatin 100mg/m2 on days 1, 22, and 43 of radiation treatments.

Those in the radiotherapy-only group received only 70 Gy of radiation.

All of the patients had stage III or IV squamous cell cancer of the supraglottic or glottic larynx that was considered curable with laryngectomy and radiotherapy. The primary outcome measure was “laryngectomy-free survival,” which was measured after a median of 10.8 years of follow-up in the current report. Late toxicity was also measured.

Overall survival at both five and 10 years was not significantly different between any of the groups, ranging from 54%-58% and 28-39%, respectively.

There was also no significant difference in the cumulative incidence of grade 3-5 toxicities between the groups. At ten years, the rates were 30.6%, 33.3% and 38% for induction chemotherapy followed by radiation, concomitant chemoradiotherapy, and radiotherapy alone, respectively.

However, in terms of larynx preservation, there was a significant advantage for concomitant cisplatin and radiotherapy, with a 54% relative risk reduction for laryngectomy compared to radiotherapy alone (p<0.001) and a 42% reduction compared with induction chemotherapy plus radiotherapy (p=0.005).

This trial was one of the largest and longest in the field to date. But head and neck cancer is a homogenous disease. “For head and neck cancers, in general, and for larynx cancer in particular, we don’t have a fully established standard,” said Dr. Jochen Lorch, a head and neck oncologist at Dana-Farber Cancer Institute in Boston who was not involved in the trial.

“My take would be this shows value in both approaches, induction and concurrent, but I think that you’re not going to get an answer about what’s the best way to treat this disease,” said Dr. Holsinger. “I definitely think that the clear value of the different approaches also opens up the path to studying minimally invasive surgery for this disease, especially neoadjuvant approaches.”

Newer induction regimens have also further clouded the picture.

“The cisplatin and 5-fluorouracil drug combination that was used in sequence with radiation has been replaced with a more effective regimen of three drugs,” said Dr. Forastiere. “We don’t yet know whether this newer induction regimen followed by radiotherapy would be as effective as concomitant treatment. That is a study that needs to be done.”

Full results of the trial were published online November 26 in the Journal of Clinical Oncology.

Source: J Clin Oncol 2012.