Superiority of tirapazamine-containing chemoradiation in head and neck cancers showing evidence of hypoxia on 18F-misonidazole (FMISO) pet scanning

Abstract

5520 Background: 45 patients were enrolled on a hypoxic imaging sub-study of a larger TROG trial in which patients with Stage III or IV SCC of the head and neck were randomized to radiotherapy (70Gy/35fx/7weeks) plus either cisplatin and infusional 5FU during weeks 6 and 7 (CIS/5FU) or the hypoxic cytotoxin, tirapazamine and cisplatin in weeks 1, 4 and 7 and tirapazamine alone in weeks 2 and 3 (CIS/TPZ) (Proc ASCO 22: 495, 2003). The objective was to determine the association between tumor hypoxia, treatment regimen and local-regional failure (LRF). Methods: Pretreatment FMISO PET was performed 2 hours after tracer administration with qualitative scoring of uptake in both primary tumours and nodes. Scores of 2 (mild) or grade 3 (moderate-high) were deemed positive for the presence of hypoxia. Results: 32 (71%) patients had detectable hypoxia in either or both primary and nodal disease. Hypoxia was present in the primary tumours of 17 of 45 (38%) patients and in the nodes of 21 of 35 (60%) node positive patients. In patients who received the CIS/5FU regimen, 1/10 without any PET evidence of hypoxia had LRF compared to 8/13 of those with hypoxia: time to LRF was significantly shorter in hypoxic patients (exact logrank P=0.038; hazard ratio (HR)= 7.1). In patients with hypoxic tumours who received the CIS/TPZ regimen, only 1/19 patients had LRF: time to LRF was significantly shorter in CIS/5FU patients with hypoxia (P=0.001; HR=15). Results at the primary site alone were as follows: in patients treated with CIS/5FU, 1/14 without hypoxia failed locally, compared to 6/9 of those with a hypoxic primary: time to primary failure was significantly shorter for hypoxic patients (P=0.018; HR=8.9). For patients with hypoxic primaries treated with CIS/TPZ 0/8 failed locally compared with 6/9 with CIS/5FU (P = 0.011). Conclusions: Hypoxic PET imaging can identify patients most likely to benefit from treatment with this tirapazamine containing chemoradiation regimen. The decreased LRF rate in patients with hypoxic tumors who received CIS/TPZ supports the hypothesis that tirapazamine acts by specifically targeting hypoxic tumour cells. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Sanofi-Synthelabo Sanofi-Synthelabo Sanofi-Synthelabo