Misonidazole combined with radiotherapy in the treatment of inoperable squamous cell carcinoma of the lung a double‐blind randomized trial

Sixty‐seven patients with inoperable squamous cell carcinoma of the lung were randomized to receive spilt‐course irradiation therapy, 40 Gy in 10 fractions over 5 weeks plus either placebo or misonidazole 1.200 mg/m2 orally on each treatment day. The target area was the primary tumor, both hilar regions, mediastinum, and both supraclavicular regions. Thirty‐three patients received misonidazole, while 34 patients received placebo. Mean observation time for the study was 27 months range, 17–36+ months. 31% of the patients in the misonidazole group obtained a complete response (CR) or a partial response (PR) as compared to 29% in the placebo group. No difference was demonstrated in the relapse pattern comparing the two groups. The death intensity was significantly higher (P = 0.03) in the misonidazole than in the placebo group, with the median survival being 4.2 and 6.7 months, respectively. Eight patients in the misonidazole group (31%) developed sensoric neuropathy while one patient in the placebo group developed irradiation myelopathy of the Brown‐Sequard type. The group of patients who later developed neuropathy had significantly higher plasma misonidazole concentrations on treatment days than the group of patients who did not. It is concluded that the combination of misonidazole and irradiation therapy for inoperable squamous cell carcinoma of the lung has no effect on response rate and relapse pattern, but a significant unexplained adverse effect on survival. Cancer 52:20‐24, 1983.