Carbogen and nicotinamide in locally advanced bladder cancer: Early results of a phase-III randomized trial

Abstract

Purpose Phase II studies in laryngeal and bladder carcinoma of accelerated radiotherapy with carbogen and nicotinamide (RT + CON) suggested a therapeutic advantage. Therefore, a randomized phase-III trial of RT + CON in locally advanced bladder carcinoma compared to radiotherapy (RT) alone was undertaken. Methods One hundred and sixty-five patients with muscle-invasive transitional cell bladder carcinoma were randomized to RT alone and 168 to RT + CON. This paper reports on compliance and toxicity to nicotinamide (NAM) and carbogen and on early radiation-induced adverse bowel and urinary events. Results Of those receiving RT + CON, 65–69% accepted all doses of NAM. Sixty-four percent of patients presented Grade ⩾1 NAM toxicity (nausea or vomiting), which was severe in 13%. Compliance to carbogen was 85% and none (32 fractions) and 2% (20 fractions) of patients presented severe toxicity. The highest prevalence of severe radiation acute morbidity was seen for urinary frequency (RT: 18% and RT + CON: 15%) and for diarrhea (RT: 3% and RT + CON: 5%). Conclusions There is no indication of an increase in radiation-induced morbidity by combining the tumour radiosensitizers carbogen and nicotinamide with radiotherapy. Late morbidity and treatment outcome will ultimately determine if there is a therapeutic benefit.