PURPOSE: "ARCON" combines accelerated radiotherapy to counteract tumor repopulation with carbogen breathing and nicotinamide to reduce chronic and acute hypoxia. The aim of this Phase II study was to assess the feasibility, toxicity, and potential effectiveness of ARCON for advanced head-and-neck cancer. METHODS AND MATERIALS: The study included 215 patients with head-and-neck carcinoma distributed as follows: larynx, n = 100; hypopharynx, n = 50; oropharynx, n = 52; oral cavity, n = 13; Stage II, n = 8, Stage III, n = 71, and Stage IV, n = 136. Accelerated radiotherapy was given to a total dose of 64-68 Gy in 2-Gy fractions within 36-38 days. This was combined with carbogen breathing during irradiation and administration of nicotinamide (60-80 mg/kg) 1-1.5 h before irradiation. RESULTS: There was full compliance with carbogen breathing in 88% of the patients. A nicotinamide dose of 80 mg/kg produced severe nausea and vomiting, necessitating discontinuation of the drug, in 31% of the patients. Adjustment of the dose to 60 mg/kg and antiemesis prophylaxis reduced the discontinuation rate to 10%. Confluent mucositis was observed in 91% of the patients with a median duration of 6 weeks. Grade 4 late complications occurred in 5% of the patients. The actuarial 3-year local control rates were 80% for larynx, 69% for hypopharynx, 88% for oropharynx, and 37% for oral cavity tumors. For T3-4 tumors, the local control rates were 80% for larynx, 60% for hypopharynx, 87% for oropharynx, and 29% for oral cavity. Regional control rates were 100% for N0, 93% for N1, and 74% for N2 disease. CONCLUSION: ARCON yields high local and regional control rates in advanced head-and-neck carcinomas, and compliance is satisfactory and morbidity acceptable. The local control rate of 80% for T3 and T4 larynx carcinomas offers excellent possibilities for organ preservation.
PURPOSE: "ARCON" combines accelerated radiotherapy to counteract tumor repopulation with carbogen breathing and nicotinamide to reduce chronic and acute hypoxia. The aim of this Phase II study was to assess the feasibility, toxicity, and potential effectiveness of ARCON for advanced head-and-neck cancer. METHODS AND MATERIALS: The study included 215 patients with head-and-neck carcinoma distributed as follows: larynx, n = 100; hypopharynx, n = 50; oropharynx, n = 52; oral cavity, n = 13; Stage II, n = 8, Stage III, n = 71, and Stage IV, n = 136. Accelerated radiotherapy was given to a total dose of 64-68 Gy in 2-Gy fractions within 36-38 days. This was combined with carbogen breathing during irradiation and administration of nicotinamide (60-80 mg/kg) 1-1.5 h before irradiation. RESULTS: There was full compliance with carbogen breathing in 88% of the patients. A nicotinamide dose of 80 mg/kg produced severe nausea and vomiting, necessitating discontinuation of the drug, in 31% of the patients. Adjustment of the dose to 60 mg/kg and antiemesis prophylaxis reduced the discontinuation rate to 10%. Confluent mucositis was observed in 91% of the patients with a median duration of 6 weeks. Grade 4 late complications occurred in 5% of the patients. The actuarial 3-year local control rates were 80% for larynx, 69% for hypopharynx, 88% for oropharynx, and 37% for oral cavity tumors. For T3-4 tumors, the local control rates were 80% for larynx, 60% for hypopharynx, 87% for oropharynx, and 29% for oral cavity. Regional control rates were 100% for N0, 93% for N1, and 74% for N2 disease. CONCLUSION: ARCON yields high local and regional control rates in advanced head-and-neck carcinomas, and compliance is satisfactory and morbidity acceptable. The local control rate of 80% for T3 and T4 larynx carcinomas offers excellent possibilities for organ preservation.
Authors: Vlad C Sandulache; Yunyun Chen; Heath D Skinner; Tongtong Lu; Lei Feng; Laurence E Court; Jeffrey N Myers; Raymond E Meyn; Clifton D Fuller; James A Bankson; Stephen Y Lai Journal: Mol Cancer Ther Date: 2015-09-16 Impact factor: 6.261
Authors: Michael Baumann; Mechthild Krause; Jens Overgaard; Jürgen Debus; Søren M Bentzen; Juliane Daartz; Christian Richter; Daniel Zips; Thomas Bortfeld Journal: Nat Rev Cancer Date: 2016-03-18 Impact factor: 60.716
Authors: Saskia E Rademakers; Paul N Span; Johannes H A M Kaanders; Fred C G J Sweep; Albert J van der Kogel; Johan Bussink Journal: Mol Oncol Date: 2008-03-27 Impact factor: 6.603
Authors: Esther G C Troost; Peter Laverman; Mariëlle E P Philippens; Jasper Lok; Albert J van der Kogel; Wim J G Oyen; Otto C Boerman; Johannes H A M Kaanders; Johan Bussink Journal: Eur J Nucl Med Mol Imaging Date: 2008-04-18 Impact factor: 9.236