Results of the German ARO/AHMO 94-01 Prospective Randomized Multicentre Trialcurrent comparing Chemoradiation with 72 Gy Hyperfractionated Accelerated Radiation Therapy (HART) plus Once Weekly DDP/5-FU versus MMC/5-FU in Locally Advanced Stage IV Head and Neck Cancer were presented at ESTRO.

25 German institutions contributed to the study funded by the "Deutsche Krebshilfe" (German Cancer Aid). Based on the previous trial ARO 95-06, (which showed distant metastases rate of more than 40% after 3 years) researchers looked at whether a concurrent once weekly DDP/5-FU-regimen would be able to improve distant metastases rates and therefore progression-free and overall survival.

For the ARO 04-01 trial, an improvement of 12% overall survival at 2 years for DDP/5-FU vs. MMC/5-FU was hypothesized from a previously closed phase-II trial based on 38 patients and data of the phase III ARO 95-06 trial based on 384 patients, respectively.

The main findings from the research showed:

• The primary endpoint of an improved OS was not reached at 2 and 3 years.
• The distant metastases-free survival was improved significantly (p=0.02, Cox' regression) after 3 years. However, no improvement in the other endpoints (PFS, LC, RC and LRC) was achieved at 3 years.
• Acute hematologic and radiation-related toxicities were not significantly different in both arms. However, creatinine values were increased for the DDP-regimen (p<0.001). Late morbidities showed not differences in both arms.
• Fourth main finding: Cost-efficiency of both presented study arms were by far better than competitive regimens, e.g. using Cetuximab or TPF-regimen.

The results of the ARO 04-01 trial indicate MMC and DDP being comparably effective for definitive chemoradiation of LAD head and neck cancer. Alternative modern induction or bio-radiation regimens seem not to be superior, in particular when considering the negative patient selection found in the ARO 04-01 trial.

The research may be indicative of a bigger trend in radiotherapy, this research shows that classical concurrent chemoradiation using DDP or MMC can be still considered the standard of care. It will be the scope of a more detailed subgroup analysis whether acute toxicity and late morbidity profiles are comparable with bio-radiation, neoadjuvant and other concurrent chemoradiation protocols. Also compliance and dose intensity issues will have to be addressed separately.

Source: ESTRO 29