CONCURRENT TIRAPAZAMINE AND RADIOTHERAPY FOR ADVANCED HEAD AND NECK CARCINOMAS - A PHASE-II STUDY

Purpose: To evaluate the efficacy and toxicity of tirapazamine, a hypo xic cytotoxin, combined with conventional radiotherapy (RT) for advanc ed head and neck carcinomas. Materials and Methods: From Oct. 1994 to Nov. 1996, 40 patients with stage III or IV carcinomas of the head and neck were enrolled in a Phase II trial to receive conventional RT (70 Gy in 7 weeks) with concurrent tirapazamine (159 mg/m(2) intravenousl y, 3 times per week for 12 doses). One patient subsequently withdrew f rom the protocol treatment, and was excluded from analyses. Among the 39 cases, the primary sites were located in the oropharynx (n = 28), s upraglottic larynx (n = 6), or hypopharynx (n = 5). Twenty-seven patie nts had T-3 or T-4, and 27 had N-2 or N-3 disease. Results: Thirty-two (82%) patients received full 12 drug doses. Thirty-two patients (82%) received full 70 Gy of RT. The most frequent drug toxicities were mus cle cramps (77%) and nausea/vomiting (62%), usually grade 1 or 2. Over all, 13 patients (33%) experienced grade 3 or 4 drug-related toxicitie s. No excessive RT-associated acute normal tissue reactions were obser ved. With a median follow-up of 13 months, the 1-year and 2-year local control rate was 64% and 59% respectively. Conclusion: The tirapazami ne regimen was well tolerated with a compliance rate of 82%. The toxic ity of RT with concurrent tirapazamine was acceptable in treating adva nced head and neck carcinomas. The disease control trend was encouragi ng. Further clinical studies are warranted. (C) 1998 Elsevier Science Inc.