Study: NCT00002774

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Tirapazamine
Description: Tirapazamine is a benzotriazine with selective cytotoxicity for hypoxic cells. Under hypoxic conditions, it undergoes a 1-electron reduction to form a cytotoxic free radical that poisons topoisomerase II and causes DNA breaks, chromosomal aberrations, and cell death.~Tirapazamine was administered on Days 1 and 22 prior to the administration of neoadjuvant cisplatin and on Days 43, 45, 47, 71, 73, and 75 within 1 or 2 hours prior to each simultaneous cisplatin dose.~Tirapazamine dose was as follows:~Level 1 - 300 mg/m2 during the induction phase and 160 mg/m2 during the simultaneous phase (n = 4)~Level 2 - 330 mg/m2 during the induction phase and 260 mg/m2 during the simultaneous phase (n = 4)~Level 3 - 300 mg/m2 during the induction phase and 220 mg/m2 during the simultaneous phase (n = 25)

Intervention type: DRUG
Group type: ACTIVE_COMPARATOR
Intervention: Cisplatin
Description: The simultaneous chemoradiotherapy (CRT) regimen included cisplatin 20 mg/m2 administered 3 times per week.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Cisplatin
Description: The simultaneous chemoradiotherapy (CRT) regimen included cisplatin 20 mg/m2 administered 3 times per week.

Intervention type: DRUG
Group type: ACTIVE_COMPARATOR
Intervention: 5-fluorouracil
Description: 100 mg/m2 per day on Days 1 and 22, and continuous infusion (CI) 5-FU at a dose of 1000 mg/m2 per day for 120 hours per cycle starting on Days 1 and 22.~The simultaneous chemoradiotherapy (CRT) regimen included continuous infusion (CI) 5-FU 600 mg/m2 per day for 96 hours per cycle in Weeks 1 and 5 of RT.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: 5-fluorouracil
Description: 100 mg/m2 per day on Days 1 and 22, and continuous infusion (CI) 5-FU at a dose of 1000 mg/m2 per day for 120 hours per cycle starting on Days 1 and 22.~The simultaneous chemoradiotherapy (CRT) regimen included continuous infusion (CI) 5-FU 600 mg/m2 per day for 96 hours per cycle in Weeks 1 and 5 of RT.

Intervention type: RADIATION
Group type: ACTIVE_COMPARATOR
Intervention: Radiotherapy (RT)
Description: During the CRT regimen, RT was given within 3 hrs of the tirapazamine infusion. The dose for the parallel opposed fields was 2 Gy/fraction/day given 5 dys/week up to a total dose of 66-70 Gy at the target lesion. The dose to the supraclavicular region was 50 Gy at a depth of 3 cm, delivered in 25 fractions. Supervoltage photons (≥4 megavolts) were used to treat both locations.~After 50 Gy were delivered to the primary site and regional lymph nodes, all sites were reassessed for clinical response by physical exam, direct fiber optic evaluation, and radiographic imaging (CT or MRI).~Subjects with a CR at both the primary site and the neck completed RT treatment to a total dose ≥66 Gy to the primary site and the involved lymph node(s). Subjects with a CR at the primary site but a partial response (PR) at the neck completed RT treatment to the primary site followed by neck dissection. Subjects with a PR at the primary site stopped radiation at 50 Gy and underwent salvage surgery.

Intervention type: RADIATION
Group type: EXPERIMENTAL
Intervention: Radiotherapy (RT)
Description: During the CRT regimen, RT was given within 3 hrs of the tirapazamine infusion. The dose for the parallel opposed fields was 2 Gy/fraction/day given 5 dys/week up to a total dose of 66-70 Gy at the target lesion. The dose to the supraclavicular region was 50 Gy at a depth of 3 cm, delivered in 25 fractions. Supervoltage photons (≥4 megavolts) were used to treat both locations.~After 50 Gy were delivered to the primary site and regional lymph nodes, all sites were reassessed for clinical response by physical exam, direct fiber optic evaluation, and radiographic imaging (CT or MRI).~Subjects with a CR at both the primary site and the neck completed RT treatment to a total dose ≥66 Gy to the primary site and the involved lymph node(s). Subjects with a CR at the primary site but a partial response (PR) at the neck completed RT treatment to the primary site followed by neck dissection. Subjects with a PR at the primary site stopped radiation at 50 Gy and underwent salvage surgery.