A phase II clinical trial of paclitaxel-carboplatin as neoadjuvant therapy followed by surgery in patients with locally advanced head and neck squamous cell carcinoma

Abstract

Background: Neoadjuvant chemotherapy (NACT) is being explored in head and neck squamous cell carcinoma (HNSCC) to improve resectability and long-term survival. This phase II study evaluated the efficacy and safety of paclitaxel-carboplatin as NACT in patients with locally advanced HNSCC. Methods: Patients with stage III-IV oral cavity, hypopharynx, larynx, or HPV-negative oropharyngeal cancer, or stage II-III HPV-positive oropharyngeal cancer received two cycles of paclitaxel (175 mg/m2) and carboplatin (AUC 5) every 3 weeks, followed by surgery. The primary endpoint was major pathologic response (MPR, <= 10 % viable tumor). Secondary endpoints included overall survival (OS), relapse-free survival (RFS), and safety. Results: Of 79 enrolled patients, 72 underwent curative-intent surgery. The MPR rate was achieved in 30.6 % (22/72), including 12.5 % with pathologic complete response (pCR). The highest MPR rate was observed in HPV-positive oropharyngeal cancer (44.7 %). Pathologic downstaging occurred in 55.6 % of patients. Median OS and RFS were not reached; 2-year OS and RFS were 89.2 % and 75.5 %, respectively. MPR was associated with numerically improved OS and RFS. Radiologic and pathologic responses were frequently discordant. Grade >= 3 adverse events occurred in 29.1 % of patients, primarily neutropenia (21.5 %), with a lower incidence observed in the pegylated granulocyte-colony stimulating factor group. Conclusions: Neoadjuvant paclitaxel-carboplatin demonstrated favorable efficacy and manageable toxicity in resectable HNSCC, with MPR and pCR rates comparable to or exceeding historical benchmarks from more intensive regimens. Although the MPR target was not met, observed outcomes compare favorably with historical controls, supporting its use as a chemotherapy backbone in future perioperative combination trials.