The early outcome results from a randomized phase III trial comparing accelerated radiotherapy (AR) with accelerated radiotherapy plus carbogen and nicotinamide (ARCON) in laryngeal cancer were presented at ESTRO, Barcelona."ARCON" combines accelerated radiotherapy to counteract tumor repopulation with carbogen breathing and nicotinamide to reduce chronic and acute hypoxia.

From April 2001 to February 2008, 345 patients with clinical stage T2-4 squamous cell laryngeal cancer were randomized to AR (N=174) and ARCON (N=171). AR was given to a total dose of 68 Gy in 2 Gy fractions within 36-38 days on the primary tumor and the pathological lymph nodes. In the experimental arm, a dose reduction to 64 Gy on the laryngeal cartilage was required and radiotherapy was combined with carbogen breathing during irradiation and administration of nicotinamide (60 mg/kg) 1-1.5 h before the first fraction of every day. After administration of the hypoxia marker pimonidazole, fresh frozen biopsies were obtained from 76 patients. The hypoxic fraction, defined as the tumor area positive for pimonidazole relative to the total tumor area was quantified after immunohistochemical staining of the tumor sections.

The results showed that after a median follow-up of 44 months (range, 1-103), local control rate at 5 years was 78% for AR versus 79% for ARCON (p=0.80). No difference was observed for glottic or supraglottic tumors. The 5-year regional control was significantly better with ARCON (86% for AR versus 93% for ARCON, p=0.04). However, this was not translated in a better overall survival (59% for AR versus 63% for ARCON, p=0.86) after 5 years. The effect of ARCON on regional control rate was most pronounced in tumors with high pimonidazole binding (60% for AR versus 100% for ARCON, p=0.01), whereas it was not significant in tumors with low pimonidazole binding (90% for AR versus 94% for ARCON, p=0.73). AR and ARCON produced equal levels of acute and severe late toxicity.

The authors of the study concluded that while levels of toxicity were equal between the treatment arms, a significant gain in regional control rate was observed in favor of ARCON for advanced laryngeal cancers. No benefit was observed for local control, which might be explained by dose reduction to 64 Gy on the larynx in the experimental arm. Based on pimonidazole binding, the hypoxic status of the primary tumor can select those patients who are most likely to benefit from ARC.

Source: ESTRO 29