Concomitant Chemoradiation Therapy
Concomitant chemoradiation therapy is a standard treatment option for locally advanced (stage III and stage IV) oropharyngeal carcinoma. A meta-analysis of 93 randomized, prospective head and neck cancer trials published between 1965 and 2000 showed a 4.5% absolute survival advantage in the subset of patients receiving chemotherapy and radiation therapy.[Level of evidence: 2A] Patients receiving concomitant chemotherapy had a greater survival benefit than those receiving induction chemotherapy.
Concomitant Radiation Therapy With Targeted Agents
In a randomized trial of locally advanced head and neck cancer patients, curative-intent radiation therapy alone (213 patients) was compared with radiation therapy plus weekly cetuximab (211 patients). The initial dose was 400 mg/m2 of body-surface area a week before starting radiation therapy followed by a weekly dose of 250 mg/m2 of body-surface area for the duration of radiation therapy. At a median follow-up of 54 months, patients treated with cetuximab and radiation therapy demonstrated significantly higher progression-free survival (hazard ratio [HR] for disease progression or death, 0.70; P = .006). Patients in the cetuximab arm experienced higher rates of acneiform rash and infusion reactions, although the incidence of other grade 3 or higher toxicities, including mucositis, did not differ significantly between the two groups. This study allowed altered-fractionation regimens to be used in both arms.[6,7][Level of evidence: 1iiA]
Induction Chemoradiation Therapy Followed by Concomitant Chemoradiation Therapy
Two published, randomized trials that compared concomitant chemoradiation therapy with induction chemotherapy followed by concomitant chemoradiation therapy for locally advanced oropharyngeal cancer failed to show a survival advantage for induction chemotherapy regimens.[8,14] However, these studies did not stratify for human papillomavirus status, and the role of induction chemotherapy remains unclear.
Radiation therapy alone with altered fractionation may be used for patients with locally advanced oropharyngeal cancer who are not candidates for chemotherapy. Altered fractionation radiation therapy yields a higher locoregional control rate than SFX for patients with stage III and stage IV oropharyngeal cancer. The long-term analysis of randomized trial RTOG-9003 included the following four radiation therapy treatment arms:
- Standard fractionation (SFX) to 70 Gy in 35 daily fractions for 7 weeks.
- Hyperfractionation (HFX) to 81.6 Gy in 68 twice-daily fractions for 7 weeks.
- Accelerated fractionation to 67.2 Gy in 42 fractions for 6 weeks with a 2-week rest after 38.4 Gy.
- Accelerated continuous fractionation (AFX-C) to 72 Gy in 42 fractions for 6 weeks.