Factors Associated with Severe Late Toxicity After Concurrent Chemoradiation for Locally Advanced Head and Neck Cancer: An RTOG Analysis

Purpose Concurrent chemoradiotherapy (CCRT) for squamous cell carcinoma of the head and neck (SCCHN) increases both local tumor control and toxicity. This study evaluates clinical factors that are associated with and might predict severe late toxicity after CCRT. Methods Patients were analyzed from a subset of three previously reported RTOG trials of concurrent chemoradiotherapy for locally advanced SCCHN (RTOG 91-11; 97-03; and 99-14). Severe late toxicity was defined in this secondary analysis as chronic Grade 3-4 pharyngeal/laryngeal toxicity (RTOG/EORTC late toxicity scoring system) and/or requirement for a feeding tube ≥2 years after registration and/or potential treatment-related death (e.g. pneumonia) within 3 years. Case-control analysis was performed, with a multivariable logistic regression model that included pre-treatment and treatment potential factors. Results A total of 230 patients were evaluable for this analysis, 99 cases (patients with severe late toxicities) and 131 controls; thus 43% of evaluable patients had a severe late toxicity. On multivariable analysis, significant variables correlated with the development of severe late toxicity were older age (odds ratio 1.05 per year; p = 0.001); advanced T-stage (odds ratio 3.07; p=0.0036); larynx/hypopharynx primary site (odds ratio 4.17; p=0.0041); and neck dissection after chemo-RT (odds ratio 2.39; p=0.018). Conclusions Severe late toxicity following CCRT is common. Older age, advanced T-stage, and larynx/ hypopharynx primary site were strong independent risk American Society of Clinical Oncology. Machtay, M. et al: J. Clin. Oncol. 26 (21), 2008:3582-3589

Phase II Evaluation of 96-Hour Paclitaxel Infusion in Advanced (Recurrent or Metastatic) Squamous Cell Carcinoma of the Head and Neck (E3395): a Trial of the Eastern Cooperative Oncology Group.

BACKGROUND: Paclitaxel (24-hour infusion) has yielded activity in advanced squamous cell carcinoma of the head and neck (SCCHN). Protracted exposure to paclitaxel may overcome resistance observed by using shorter infusions. Therefore we sought to evaluate paclitaxel by 96-hour infusion in both treatment-naïve and previously treated patients with SCCHN. MATERIALS AND METHODS: Eligibility stipulated bi-dimensionally measurable, biopsy-documented, incurable SCCHN, Eastern Cooperative Oncology Group performance status (PS) 0-1, and adequate physiological indices. Patients were divided into three cohorts: 1) chemotherapy-naïve; 2) chemotherapy-exposed, paclitaxel-naïve; and 3) chemotherapy and paclitaxel exposed. Paclitaxel was dosed at 140 mg/m2 (96-hour infusion) every 3 weeks in treatment-naïve patients and at 120 mg/m2 (96 hours) every 3 weeks in previously treated patients. RESULTS: Fifty patients were accrued between February 1997 and July 2000. The study was terminated because of low response rate. Eighty percent of patients were male, 75% PS 1. Nearly half the patients had oropharyngeal or hypopharyngeal primary sites. There was one treatment-related death due to neutropenic fever/pneumonia. Grade 4 toxicities included granulocytopenia in eight patients (20%), thrombocytopenia, and stomatitis in one patient each. Grade 3 or greater anemia occurred in 10 patients. There was no grade 2 or 3 peripheral sensory neuropathy. In 15 chemotherapy-naïve patients, two responses (13%) were observed. There were no responses in treatment-exposed patients. The overall median survival was 5.5 months, and 1-year survival rate 10%. Treatment-naïve patients had a median survival of 8.2 months and 1-year survival rate of 20%. CONCLUSIONS: Paclitaxel by 96-hour infusion at a dose of 120-140 mg/m2/96 hours is only marginally active in the treatment of SCCHN. This dose and schedule cannot be recommended for further evaluation