Showing papers by "James A. Bonner published in 2016"
TL;DR: In this article, a retrospective evaluation of the IMCL-9815 study was conducted to examine the association of human papillomavirus (HPV) and p16 protein expression status with outcomes in patients with oropharyngeal carcinoma (OPC) receiving radiotherapy (RT) plus cetuximab or RT alone.
Abstract: PurposeWe conducted a retrospective evaluation of the IMCL-9815 study to examine the association of human papillomavirus (HPV) and p16 protein expression status with outcomes in patients with oropharyngeal carcinoma (OPC) receiving radiotherapy (RT) plus cetuximab or RT alone.Patients and MethodsIn the IMCL-9815 study, patients were randomly allocated to receive RT plus weekly cetuximab or RT alone. A subpopulation of patients with p16-evaluable OPC was retrospectively evaluated on the basis of locoregional control (LRC), overall survival (OS), and progression-free survival (PFS). Evaluable samples from patients with p16-positive OPC were also tested for HPV DNA.ResultsTumor p16 status was evaluable in 182 patients with OPC enrolled in the IMCL-9815 study; 41% were p16 positive. When treated with RT alone or RT plus cetuximab, p16-positive patients had a longer OS than p16-negative patients (hazard ratio, 0.40; 95% CI, 0.21 to 0.74 and hazard ratio, 0.16; 95% CI, 0.07 to 0.36, respectively). The addition ...
184 citations
TL;DR: The results of a possible cetuximab-related laryngeal preservation benefit for patients with hypopharynx or larynGEal cancer are intriguing; these results need to be interpreted in the context of a retrospective subset analysis with limited sample size.
Abstract: Importance The appropriate use of surgery or radiotherapy-based approaches for organ preservation has been the subject of much debate. Unfortunately, there has been a lack of improvement in overall survival for patients with laryngeal carcinoma in the last 30 years. Objective To assess the rates of laryngeal preservation and laryngectomy-free survival in patients receiving cetuximab and radiotherapy (CRT) and patients receiving radiotherapy alone. Design, Setting, and Participants Patients were enrolled in a multicenter, open-label, stratified, randomized, phase 3 study from April 1, 1999, through March 31, 2002, from 73 centers in the United States and 14 other countries. A secondary subgroup analysis of patients with hypopharyngeal and laryngeal carcinoma was undertaken. Rates of laryngeal preservation and laryngectomy-free survival were estimated by the Kaplan-Meier method. The hazard ratios (HRs) were calculated using a Cox proportional hazards regression model. Quality of life was evaluated using the European Organization for Research and Treatment of Cancer core questionnaire and head and neck module. Main Outcomes and Measures Laryngeal preservation and laryngectomy-free survival. Results Of the 424 patients included in the trial, 168 treated patients with cancer of the larynx or hypopharynx were included in this analysis (90 in the CRT group and 78 in the radiotherapy alone group). The median (range) age of the patients was 59 (40-80) years in the CRT group and 61 (35-81) years in the radiotherapy alone group. In the CRT group, 72 patients (80.0%) were male and 18 (20.0%) were female. In the radiotherapy alone group, 62 (79.5%) were male and 16 (20.5%) were female. The rates of laryngeal preservation at 2 years were 87.9% for CRT vs 85.7% for radiotherapy alone, with an HR of 0.57 (95% CI, 0.23-1.42; P = .22). Similarly, the HR for laryngectomy-free survival comparing CRT vs radiotherapy alone was 0.78 (95% CI, 0.54-1.11; P = .17). This study was not powered to assess organ preservation. Median overall survival was 27 (95% CI, 20-45) vs 21 (95% CI, 17-35) months for the CRT and radiotherapy alone groups, respectively, with an HR of 0.87 (95% CI, 0.60-1.27). No differences between treatments were reported regarding overall quality of life, need for a feeding tube, or speech. Conclusions and Relevance The results of a possible cetuximab-related laryngeal preservation benefit for patients with hypopharyngeal or laryngeal cancer are intriguing; these results need to be interpreted in the context of a retrospective subset analysis with limited sample size. Trial Registration clinicaltrials.gov Identifier: NCT00004227
37 citations
TL;DR: Regardless of p16 status, the addition of cetuximab to RT did not alter the incidence, time to onset, severity, or duration of mucositis and dysphagia and did not impact the frequency of feeding tube use.
27 citations
TL;DR: Recently, Magrini et al. reported the results of a small randomized phase II study that included 70 patients with locoregionally advanced head and neck cancer who were randomly assigned to treatment with weekly cisplatin and radiotherapy or cetuximab and RT.
Abstract: Recently, Magrini et al. reported the results of a small randomized phase II study that included 70 patients with locoregionally advanced head and neck cancer who were randomly assigned to treatment with weekly cisplatin and radiotherapy (RT) or cetuximab and RT (1).
4 citations
Johns Hopkins University1, Ohio State University2, University of Texas MD Anderson Cancer Center3, Washington University in St. Louis4, University of California, San Francisco5, Medical College of Wisconsin6, Fox Chase Cancer Center7, Memorial Sloan Kettering Cancer Center8, University of Alabama at Birmingham9, University of Colorado Boulder10, Radiation Therapy Oncology Group11, Stanford University12
TL;DR: Therapeutic de-intensification for OPC underscores the need for accurate patient-specific assessment of risk, and current risk stratification is based on HPV tumor status, tobacco use, and other factors.
Abstract: 6024Background: Therapeutic de-intensification for OPC underscores the need for accurate patient-specific assessment of risk. Current risk stratification is based on HPV tumor status, tobacco use, ...
2 citations
University of Texas MD Anderson Cancer Center1, Washington University in St. Louis2, Thomas Jefferson University Hospital3, Medical College of Wisconsin4, Université de Montréal5, Fox Chase Cancer Center6, Wayne State University7, University of California, San Francisco8, University of Colorado Denver9, University of Alabama at Birmingham10, Case Western Reserve University11, Stanford University12
2 citations
TL;DR: Celecoxib appears to be a safe addition to cisplatin-based chemoradiotherapy for the primary treatment of locoregionally advanced SCCHN and initial response rates were encouraging, and survival compared favorably with contemporary trials.
Abstract: We performed this open-label phase I/II trial to investigate concurrent celecoxib as a radiosensitizer during chemoradiotherapy. Eligible patients included those with newly diagnosed, or recurrent, stage III or IVA locoregionally advanced squamous cell carcinoma of the head-and-neck (SCCHN), excluding nasopharyngeal tumors. The primary tumor was prescribed 70.2 Gy with concurrent weekly carboplatin and paclitaxel. Celecoxib was dosed at 400 mg twice daily, beginning 1 week prior to radiotherapy. Thirty patients were enrolled between 2002 and 2007. The median age at enrollment was 57.6 years, and the median follow-up for surviving patients was 10.4 years (range 5.9–11.8 years). The complete clinical response rate was 87 %, nearly achieving the primary end point goal of 90 %. The 5-year actuarial disease-free survival (DFS) and overall survival (OS) were 40 and 53.3 %. Fourteen (47 %) patients experienced grade 3 or worse acute hematologic toxicity. Five (17 %) patients experienced grade 4 acute non-hematologic toxicity. Celecoxib appears to be a safe addition to cisplatin-based chemoradiotherapy for the primary treatment of locoregionally advanced SCCHN. Initial response rates were encouraging, and survival compared favorably with contemporary trials. Unfortunately, concern for cardiac toxicity of the drug led to early closure and limited statistical significance.