Phase II trial of chemoradiation for organ preservation in resectable stage III or IV squamous cell carcinomas of the larynx or oropharynx: results of Eastern Cooperative Oncology Group Study E2399.

PURPOSE: Taxane-based concurrent chemoradiotherapy (CCR) for head and neck cancers has proven to have a favorable toxicity profile compared with cisplatin and radiation. This phase II multi-institutional trial evaluates taxane-based induction chemotherapy followed by CCR for organ preservation in resectable stage III/IVA and IVB larynx and oropharynx (OP) cancer patients. PATIENTS AND METHODS: Eligibility required resectable stage T2N+, or T3-T4N0-3M0 biopsy-proven squamous carcinoma, age at least 18 years, PS 0 to 2, good organ function, and no prior chemotherapy or radiation. Treatment was induction paclitaxel 175 mg/m(2) and carboplatin area under the concentration-time curve (AUC) 6 for two cycles every 21 days followed by concurrent paclitaxel 30 mg/m(2) every 7 days with 70 Gy if no evidence of tumor progression. Weekly erythropoietin alpha 40 kU was used for suboptimal hemoglobin (< 14 gm/dL men, < 13 gm/dL women). The primary end point was organ preservation (freedom from primary site salvage surgery or primary tumor recurrence).
RESULTS: One hundred five of 111 patients (36 larynx, 69 OP) were eligible. Median follow-up was 36.7 months. Ninety-four percent received full-dose radiotherapy and 91% received at least five cycles of concurrent paclitaxel. No patient progressed while receiving chemotherapy. Organ preservation was 81% at 2 years after completion of therapy (larynx 74%, OP 84%). Thirteen patients required primary-site salvage surgery (seven larynx, six OP), and six of these have progressed and died (three larynx, three OP). Thirteen patients developed distant metastases (seven larynx, six OP; P = .02) and 10 of 36 larynx and 11 of 69 OP patients have died as a result of their disease. Two-year survival is 76% (63% larynx v 83% OP).
CONCLUSION: A high organ preservation rate was obtained with this regimen for OP but not for larynx patients. Toxicity was low, and induction chemotherapy did not preclude delivery of concurrent chemoradiotherapy.