BARCELONA – Mitomycin C proved as effective and well tolerated as cisplatin when used as part of a chemoradiation schedule for locally advanced stage IV head and neck cancer, but it was associated with more distant metastases at 3 years.
Results of a randomized, phase III trial indicate that “classical concurrent chemoradiation using cisplatin or MMC [mitomycin C] can still be considered the standard of care,” said study investigator Dr. Volker Budach, head of the radiation oncology department at Charité Medical University Berlin.
“This trial has established, for the first time, level Ib evidence for a concurrent, once-weekly cisplatin/[5-fluorouracil] regimen with a moderate, accelerated, radiation strategy,” he added, addressing the biennial meeting of the European Society for Therapeutic Radiation and Oncology (ESTRO 29).
An invited discussant of the trial, Dr. Hans Langendijk noted that it was “the first phase III study in head and neck cancer that compared two different chemotherapy regimens in combination with a hypofractionated accelerated radiation schedule.”
Platinum-based, concomitant chemoradiation is considered the standard of care, but it is associated with considerable toxicity, and this has prompted the search for suitable alternative strategies, commented Dr. Langendijk, professor of radiotherapy at the University Medical Center Groningen (the Netherlands), who was not involved in the trial.
In the German Clinical Trials Cooperative Group’s ARO/AHMO 04-01 trial, 364 patients with stage IV head and neck cancer were randomized to receive chemoradiation consisting of 72-Gy hyperfractionated accelerated radiation therapy (HART) plus either concurrent cisplatin and 5-fluorouracil (5-FU) or MMC/5-FU for 6 weeks.
At 3 years’ follow-up, more patients who received weekly chemoradiation with cisplatin than MMC were free of distant metastases (hazard ratio, 0.622; P = .02). The primary end point of the trial (an improvement in overall survival) was not reached at 2 or 3 years, however, and cisplatin with 5-FU was not superior to MMC/5-FU in terms of any of the other end points assessed, which included progression-free survival, local control, regional control, and locoregional recurrence.
The local control rate was about 70%, as Dr. Budach reported, with regional and locoregional control rates of approximately 80% and 60%, respectively. “These are excellent values, and can easily compare” with those in other published trials, he said.
Acute hematologic or radiation-related toxicities were also not significantly different between the two study arms, although Dr. Budach highlighted that cisplatin-treated patients had higher creatinine levels than did those who were treated with MMC (P = .001).
“The cost:efficiency ratio is excellent due to the off-license use of all involved drugs, and far better than competitive regimens,” which include cetuximab (Erbitux) as well as the TPF (docetaxel [Taxotere], cisplatin, and 5-FU) regimen, Dr. Budach said.
Commenting on the data in an interview, ESTRO president Dr. Jean Bourhis said, “It’s interesting, because when you compare the two regimens, they are not too different except for the effects on distant metastases.” Dr. Bourhis, chairman of the radiation oncology department at the Institut Gustave Roussy in Villejuif, France, added that this finding could sway some clinicians toward the use of cisplatin rather than MMC.
However, considering that there was no difference in efficacy findings and fewer renal failures, “HART plus MMC/5-FU could be considered as a standard of care,” said Dr. Langendijk. He suggested that cetuximab plus radiotherapy could also be considered as a standard of care in patients for whom platinum-based chemotherapy is not an option.
“Further analysis is needed on specific subsets of patients,” Dr. Langendijk said, notably to see whether HPV status makes any difference in the effects of the MMC/5-FU combination.
Disclosures: Deutsche Krebshilfe (German Cancer Aid) funded the study. The investigators, Dr. Bourhis, and Dr. Langendijk had no conflicts of interest.