Radiation Therapy and Combination Chemotherapy in Treating Patients With Stage III or Stage IV Head and Neck Cancer

Summary

PURPOSE: Randomized phase 2 trial to compare the effectiveness of chemo-radiation therapy (RT + cisplatin + 5-FU) with or without tirapazamine for the treatment of patients with stage III or IV squamous cell carcinomas of the head and neck cancer (SCCHN).

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. Radiation therapy uses high-energy x-rays to damage tumor cells.

Tirapazamine may increase the effectiveness of chemotherapy and radiation therapy by making tumor cells more sensitive to therapy.

Conditions

• Squamous Neck Carcinoma of the Head and Neck Cancer (SCCHN)

Interventions

DRUG

Tirapazamine

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)

DRUG

Cisplatin

The simultaneous chemoradiotherapy (CRT) regimen included cisplatin 20 mg/m2 administered 3 times per week.

DRUG

5-fluorouracil

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.

RADIATION

Radiotherapy (RT)

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.

Sponsors & Collaborators

• National Cancer Institute (NCI)

  collaborator NIH

• Stanford University

  lead OTHER

Principal Investigators

• Harlan A. Pinto, MD · Stanford University

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Model

PARALLEL

Eligibility

Min Age

17 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

1996-06-30

Primary Completion

2000-06-30

Completion

2005-06-30

Countries

• United States

Study Locations