A Phase II trial of radiotherapy with concurrent tirapazamine, a hypoxic cytotoxin, for advanced head and neck carcinomas

Objectives: To evaluate the efficacy and toxicity of tirapazamine, a hypoxic cytotoxin, combined with conventional radiotherapy for advanced head and neck carcinomas, in a prospective Phase II study. Materials and Methods: Between Oct., 1994 and Feb., 1996, 24 patients from multiple institutions with advanced stage 3 or 4 carcinomas of the oropharynx (n=19), hypopharynx (n=3) or supraglottic larynx (n=2) had enrolled in a Phase II trial to receive conventional external beam radiotherapy (70 Gy in 7 weeks) with concurrent tirapazamine (159 mg/m2 iv, 3 times per week for 12 doses). All of them had a biopsy proven squamous carcinoma which was previously untreated. Results: The drug regimen was tolerable with only 2 of 24 patients received less than the full dose. Main drug toxicities were muscle cramps (86%), nausea (77%) and vomiting (27%) which usually could be ameliorated by appropriate medications. Only 9% of patients experienced Grade 3 and none had grade 4 toxicities. No excessive radiation induced acute reactions were observed. 14 patients had at least one month follow-up (median 7 months, range: 1 to 15 months), and in all of them (100%) a local-regional control was achieved. Conclusion: Tirapazamine with concurrent radiotherapy was well tolerated with acceptable toxicities for treating head and neck carcinomas. The preliminary local-regional control rate was excellent. These results indicate that a Phase III trial is warranted. Results will be updated